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Zou Z, Zhao W, Chen Y, Liu Z, He G, Zhang H. Extracorporeal membrane oxygenation in the treatment of critical Pneumocystis jirovecii pneumonia in a child with Langerhans cell histiocytosis: a case report and literature review. BMC Infect Dis 2025; 25:492. [PMID: 40205543 PMCID: PMC11983937 DOI: 10.1186/s12879-025-10893-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 04/02/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Children with Langerhans cell histiocytosis (LCH) are particularly susceptible to infections such as Pneumocystis jirovecii pneumonia (PJP) due to the immunosuppressive effects of chemotherapy, which can progress to acute respiratory distress syndrome (ARDS) and respiratory failure. The use of Extracorporeal Membrane Oxygenation (ECMO) to manage hypoxemia secondary to PJP in LCH presents unique challenges, including the prevention of catheter-related bloodstream infections associated with arterial and venous access. This study explores a case wherein ECMO was crucial in treating severe PJP-induced respiratory failure in a pediatric patient with LCH. CASE PRESENTATION A 3-year-old female with a history of LCH, undergoing long-term chemotherapy and corticosteroid treatment, was admitted with fever, dyspnea, and lethargy. Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid confirmed Pneumocystis jirovecii (PJ). Despite aggressive management with invasive high-frequency ventilation, inhaled nitric oxide, and prone positioning, the patient's oxygenation remained critically low, with severe hypercapnia and resultant severe respiratory acidosis, necessitating vasopressor support for hemodynamic stability and venoarterial (VA) ECMO intervention. Early initiation of VA ECMO facilitated ultraprotective lung ventilation and circulatory support, effectively preventing hemodynamic collapse. The patient was successfully decannulated after 13 days of ECMO support. CONCLUSION While PJP is a rare and extremely serious opportunistic infection, the VA ECMO support in this pediatric case effectively managed severe PJP without ECMO-related complications. This highlights ECMO as a potentially viable, relatively effective, and safe adjunctive therapy in the management of severe PJP infections in children.
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Affiliation(s)
- Zhuan Zou
- Department of Emergency, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Wanlin Zhao
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Yulin Chen
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Zhongqiang Liu
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Guoqian He
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Haiyang Zhang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
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Mirmohammad Sadeghi H, Gholami Toghchi S, Mashhadiabbas F, Baseri M, Mohammadalizadeh Chafjiri M, Nikraftar P, Khorsand A. Polyostotic Langerhans cell histiocytosis presenting as halitosis in a 24-year-old man: a case report. J Med Case Rep 2025; 19:155. [PMID: 40181439 PMCID: PMC11969994 DOI: 10.1186/s13256-025-05062-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 12/13/2024] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND Langerhans cell histiocytosis is a rare disease of the reticuloendothelial system. This report presents a novel case of Langerhans cell histiocytosis with systemic involvement that started with a simple chief complaint. The reporting of this case raises awareness of the distinctive characteristics of this challenging disorder. CASE PRESENTATION A 24-year-old male patient of Persian ethnicity presented with a chief complaint of halitosis following coronavirus disease 2019 recovery to his general dentist's office. Intraoral and extraoral examinations revealed no specific problem. In the follow-up session after phase I periodontal treatment, teeth sensitivity to cold stimulus was evident, and radiographs revealed a large lytic intraosseous lesion in the mandible. An incisional biopsy revealed Langerhans cells and a positive reaction to Langerin and cluster of differentiation 1a, thus, he was diagnosed with Langerhans cell histiocytosis. After performing positron emission tomography with fluoro-2-deoxyglucose and computed tomography, magnetic resonance imaging, and cone beam computed tomography, owing to generalized disease involvement, the patient was referred to an oncologist. Ultimately, it was found that the patient's childhood health issues, including endocrine problems, were likely caused by an undiagnosed Langerhans cell histiocytosis. The oncologist chose denosumab, vinblastine, etoposide, 6-mercaptopurine, methotrexate, and pegfilgrastim regimen. The follow-up was not possible as the patient died following an accident. CONCLUSION This reveals the vitality of the early diagnosis of Langerhans cell histiocytosis to prevent disease progression. Awareness of diverse and nonpathognomonic manifestations of Langerhans cell histiocytosis, proper medical interview and history taking, and the use of routine radiographs may aid clinicians in lowering morbidity and mortality rates associated with such conditions.
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Affiliation(s)
- Hassan Mirmohammad Sadeghi
- Department of Oral and Maxillofacial Surgery, Dentistry Faculty, Shahid Beheshti University of Medical Sciences, Velenjak St., Shahid Chamran Highway, Tehran, 1985717443, Iran
| | - Sanaz Gholami Toghchi
- Department of Oral and Maxillofacial Pathology, Dentistry Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mashhadiabbas
- Department of Oral and Maxillofacial Pathology, Dentistry Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Milad Baseri
- Department of Oral and Maxillofacial Surgery, Dentistry Faculty, Shahid Beheshti University of Medical Sciences, Velenjak St., Shahid Chamran Highway, Tehran, 1985717443, Iran
| | | | - Parnian Nikraftar
- Department of Radiology, Medicine Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ardeshir Khorsand
- Department of Oral and Maxillofacial Surgery, Dentistry Faculty, Shahid Beheshti University of Medical Sciences, Velenjak St., Shahid Chamran Highway, Tehran, 1985717443, Iran.
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Singh SR, Bhaskar R, Ghosh S, Yarlagadda B, Singh KK, Verma P, Sengupta S, Mladenov M, Hadzi-Petrushev N, Stojchevski R, Sinha JK, Avtanski D. Exploring the Genetic Orchestra of Cancer: The Interplay Between Oncogenes and Tumor-Suppressor Genes. Cancers (Basel) 2025; 17:1082. [PMID: 40227591 PMCID: PMC11988167 DOI: 10.3390/cancers17071082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 03/17/2025] [Accepted: 03/20/2025] [Indexed: 04/15/2025] Open
Abstract
Cancer is complex because of the critical imbalance in genetic regulation as characterized by both the overexpression of oncogenes (OGs), mainly through mutations, amplifications, and translocations, and the inactivation of tumor-suppressor genes (TSGs), which entail the preservation of genomic integrity by inducing apoptosis to counter the malignant growth. Reviewing the intricate molecular interplay between OGs and TSGs draws attention to their cell cycle, apoptosis, and cancer metabolism regulation. In the present review, we discuss seminal discoveries, such as Knudson's two-hit hypothesis, which framed the field's understanding of cancer genetics, leading to the next breakthroughs with next-generation sequencing and epigenetic profiling, revealing novel insights into OG and TSG dysregulation with opportunities for targeted therapy. The key pathways, such as MAPK/ERK, PI3K/AKT/mTOR, and Wnt/β-catenin, are presented in the context of tumor progression. Importantly, we further highlighted the advances in therapeutic strategies, including inhibitors of KRAS and MYC and restoration of TSG function, despite which mechanisms of resistance and tumor heterogeneity pose daunting challenges. A high-level understanding of interactions between OG-TSGs forms the basis for effective, personalized cancer treatment-something to strive for in better clinical outcomes. This synthesis should integrate foundational biology with translation and, in this case, contribute to the ongoing effort against cancer.
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Affiliation(s)
| | - Rakesh Bhaskar
- School of Chemical Engineering, Yeungnam University, Gyeongsan-si 38541, Republic of Korea;
- Research Institute of Cell Culture, Yeungnam University, Gyeongsan-si 38541, Republic of Korea
| | - Shampa Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
| | | | - Krishna Kumar Singh
- Symbiosis Centre for Information Technology (SCIT), Symbiosis International (Deemed University), Rajiv Gandhi InfoTech Park, Hinjawadi, Pune 411057, India
| | - Prashant Verma
- School of Management, BML Munjal University, NH8, Sidhrawali, Gurugram 122413, India
| | - Sonali Sengupta
- Department of Gastroenterology, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India
| | - Mitko Mladenov
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia
| | - Nikola Hadzi-Petrushev
- Faculty of Natural Sciences and Mathematics, Institute of Biology, Ss. Cyril and Methodius University, 1000 Skopje, North Macedonia
| | - Radoslav Stojchevski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
| | | | - Dimiter Avtanski
- Friedman Diabetes Institute, Lenox Hill Hospital, Northwell Health, New York, NY 10022, USA
- Feinstein Institutes for Medical Research, Manhasset, NY 11030, USA
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
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Zhang Z, Wang J, Shi Y, Zhao Y, Hu Y, Wang W, Chen Z. Progress in investigating pituitary stalk lesions: A review. Medicine (Baltimore) 2025; 104:e41232. [PMID: 39792770 PMCID: PMC11729155 DOI: 10.1097/md.0000000000041232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Accepted: 11/07/2024] [Indexed: 01/12/2025] Open
Abstract
Pituitary stalk lesions are uncommon and are typically identified through pituitary magnetic resonance imaging and screening for causes of diabetes insipidus. Recent literature indicates that pituitary stalk lesions primarily manifest as pituitary stalk interruption syndrome and thickening of the pituitary stalk. The etiology of these lesions is complex and can be divided into major categories: congenital disorders, inflammatory or infectious diseases, and tumors. Therefore, achieving accurate diagnosis, differential diagnosis, and treatment for pituitary stalk lesions is crucial. This article aims to classify pituitary stalk lesions and delve into the latest research on their etiology, pathological mechanisms, clinical manifestations, diagnosis, and treatment of associated diseases.
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Affiliation(s)
- Zaidong Zhang
- Department of Hepatobiliary Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong, P.R. China
| | - Jinlin Wang
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong, P.R. China
| | - Yaru Shi
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong, P.R. China
| | - Yahui Zhao
- Department of Clinical Medicine, Jining Medical University, Jining, Shandong, P.R. China
| | - Yanli Hu
- Department of Emergency Medicine, Linyi People’s Hospital, Linyi, Shandong, P.R. China
| | - Wentao Wang
- Department of Geriatrics, Taian Central Hospital, Taian, Shandong, P.R. China
| | - Zonglan Chen
- Department of Endocrinology and Metabolism, Affiliated Hospital of Jining Medical University, Jining, Shandong, P.R. China
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Rajabi MT, Abdol Homayuni MR, Samiee R, Mobader Sani S, Aghajani AH, Rafizadeh SM, Amanollahi M, Pezeshgi S, Hosseini SS, Rajabi MB, Sadeghi R. Orbital histiocytosis; From A to Z. Int Ophthalmol 2024; 44:236. [PMID: 38902584 DOI: 10.1007/s10792-024-03179-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 06/15/2024] [Indexed: 06/22/2024]
Abstract
PURPOSE Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.
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Affiliation(s)
- Mohammad Taher Rajabi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
| | - Mohammad Reza Abdol Homayuni
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- NCweb Association, Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Reza Samiee
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Sheida Mobader Sani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- NCweb Association, Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Hossein Aghajani
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
| | - Seyed Mohsen Rafizadeh
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
| | - Mobina Amanollahi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Saharnaz Pezeshgi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Simindokht Hosseini
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
| | - Mohammad Bagher Rajabi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran
| | - Reza Sadeghi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Qazvin Square, Tehran, 1336616351, Iran.
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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6
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Casal A, Suárez-Antelo J, Riveiro V, Ferreiro L, Rodríguez-Núñez N, Toubes ME, Valdés L. Smoking-related interstitial lung disease: A narrative review. Chron Respir Dis 2024; 21:14799731241291538. [PMID: 39423337 PMCID: PMC11492237 DOI: 10.1177/14799731241291538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 09/14/2024] [Accepted: 09/24/2024] [Indexed: 10/21/2024] Open
Abstract
Although smoking-related interstitial lung diseases (SR-ILD) are a relatively rare group of entities, they are a relevant public health problem of growing importance, both because they affect young adults and because of their increasing prevalence in recent years due to increased tobacco consumption. In patients who smoke and have non-specific respiratory symptoms, SR-ILD should be ruled out, a term that encompasses a group of different entities in which the basis for diagnosis is the smoking history together with compatible respiratory functional findings, radiology and/or histology. An association has been established between tobacco smoke and a group of diseases that include respiratory bronchiolitis-associated interstitial lung disease (2%-3% of all ILD), desquamative interstitial pneumonia (<1%), Langerhans cell histiocytosis (3%-5%) and acute eosinophilic pneumonia. Smoking is considered a risk factor for idiopathic pulmonary fibrosis which has also been called combined fibroemphysema (5%-10% of all ILD); however, the role and impact of smoking in its development, remains to be determined. The likely interconnection between the mechanisms involved in inflammation and pulmonary fibrosis in all these processes often results in an overlapping of clinical, radiological, and histological features. In the absence of robust scientific evidence on its management, smoking cessation is the first measure to be taken into account. Although most diseases have a benign clinical course after smoking cessation, some cases may progress to chronic respiratory failure.
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Affiliation(s)
- Ana Casal
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | - Juan Suárez-Antelo
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | - Vanessa Riveiro
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | - Lucía Ferreiro
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
- Santiago de Compostela Health Research Institute (IDIS), Santiago de Compostela, Spain
| | - Nuria Rodríguez-Núñez
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | - María E. Toubes
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
| | - Luis Valdés
- Department of Pneumology, Santiago de Compostela University Hospital Complex, Santiago de Compostela, Spain
- Santiago de Compostela Health Research Institute (IDIS), Santiago de Compostela, Spain
- Department of Medicine, University of Medicine of Santiago de Compostela, Santiago de Compostela, Spain
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7
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Acosta-Medina AA, Abeykoon JP, Go RS, Goyal G, Ravindran A, Schram SM, Rech KL. BRAF testing modalities in histiocytic disorders: Comparative analysis and proposed testing algorithm. Am J Clin Pathol 2023; 160:483-489. [PMID: 37458275 DOI: 10.1093/ajcp/aqad076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 06/01/2023] [Indexed: 11/08/2023] Open
Abstract
OBJECTIVES Understanding of histiocytic disorders has been revolutionized by demonstration of mitogen-activated protein kinase (MAPK) pathway mutations, most commonly BRAFV600E. The optimal testing strategy to assess BRAFV600E is unknown. We aimed to compare performance of testing modalities, to propose a framework for evaluation of BRAFV600E mutation status in histiocytic disorders. METHODS We retrospectively reviewed patients with histiocytic disorders and BRAF mutation testing on a lesional tissue specimen. RESULTS In 120 patients, BRAF assessment included immunohistochemistry (IHC) in 97 (80.2%), polymerase chain reaction (PCR) in 35 (28.9%), and next-generation sequencing (NGS) in 62 (51.2%). Forty-five underwent both NGS and IHC. With NGS as the gold standard, the sensitivity and specificity of IHC were 82.4% and 96.4%. Three false negatives were observed in biopsy specimens with low BRAFV600E variant allele frequency or decalcified tissue. One false-positive IHC was observed in a lung biopsy specimen, likely due to antibody cross-reactivity with respiratory cilia. Among 14 with successful NGS and PCR, a single discordance was observed. Two PCR-to-IHC discrepancies were observed, including one other false-positive IHC. CONCLUSIONS Immunohistochemistry was highly specific for detection of BRAFV600E. Main caveats were false negatives and lack of detection of non-BRAFV600E mutations. We propose the use of IHC as initial screening in general practice with reflex molecular testing if negative.
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Affiliation(s)
| | | | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN, US
| | - Gaurav Goyal
- Division of Hematology-Oncology and University of Alabama at Birmingham, Birmingham, AL, US
| | - Aishwarya Ravindran
- Division of Laboratory Medicine, University of Alabama at Birmingham, Birmingham, AL, US
| | | | - Karen L Rech
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, US
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Wang Q, Bradley K, Zhang M, Li S, Li X. Rosai-Dorfman disease of the breast: a clinicoradiologic and pathologic study. Hum Pathol 2023; 141:30-42. [PMID: 37673345 DOI: 10.1016/j.humpath.2023.08.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 08/26/2023] [Accepted: 08/31/2023] [Indexed: 09/08/2023]
Abstract
Rosai-Dorfman disease (RDD) is an uncommon histiocytic disorder typically involving lymph nodes and less frequently extranodal tissues. RDD involving the breast is rare and may clinically and radiologically mimic neoplastic and non-neoplastic disorders. We report seven patients with breast RDD, describe their clinicoradiologic and pathologic features, and discuss the differential diagnosis. Patients, ranging from 15 to 74 years of age, presented with unilateral and unifocal (5/7) or bilateral and multifocal (2/7) masses. RDD was either confined to the breast (6/7) or concurrently involved a lymph node (1/7). Masses ranged from 8 to 31 mm, categorized as Breast Imaging-Reporting and Data System (BI-RADS) 4 (6/7) or 5 (1/7). All cases showed similar morphology with many large histiocytes displaying emperipolesis with associated fibrosis and dense lymphoplasmacytic infiltrate. The abnormal histiocytes co-expressed CD68/CD163, S100, OCT2, and Cyclin D1 (7/7), and were negative for CK AE1/AE3 (7/7), CD1a (7/7), and BRAF V600E (6/6). Flow cytometry (n = 3), kappa/lambda in situ hybridization (n = 5), and IgG4/IgG immunohistochemistry (n = 1) did not reveal lymphoma or IgG4-related disease. No mycobacterial or fungal organisms were identified on acid-fast bacillus (AFB) and Grocott methenamine silver (GMS) stains (n = 5). Three patients underwent complete excision and none recurred or progressed to systemic disease during follow-up (88-151 months). In summary, breast RDD should be included in the differential diagnosis of a mass-forming breast lesion. Histopathology with ancillary studies and clinicoradiologic correlation is essential for accurate diagnosis and optimal clinical management. Patients with RDD of the breast have an excellent prognosis after complete excision.
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Affiliation(s)
- Qun Wang
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
| | - Kyle Bradley
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Meng Zhang
- Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Shiyong Li
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA
| | - Xiaoxian Li
- Department of Pathology, Emory University School of Medicine, Atlanta, GA, 30322, USA.
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Vargas JC, Cardozo C, Stanzione R, Fiore L, D'Almeida Costa F, Fonseca Abreu R, Hamerschlak N, Perini G. Incidental Diagnosis of Oligosymptomatic Bilateral Perirenal Erdheim-Chester Disease during Emergency Investigation for COVID-19 Infection. Case Rep Hematol 2023; 2023:4683188. [PMID: 37303482 PMCID: PMC10257540 DOI: 10.1155/2023/4683188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Revised: 04/20/2023] [Accepted: 05/18/2023] [Indexed: 06/13/2023] Open
Abstract
Erdheim-Chester disease (ECD), a rare form of non-Langerhans histiocytosis, is a multisystem disorder. The case reported here refers to a 49-year-old man presenting at the emergency room with respiratory symptoms. While undergoing diagnostic tests for COVID-19 infection, tomography revealed asymptomatic bilateral perirenal tumors, while renal function remained unaltered. ECD was suggested as an incidental diagnosis and confirmed by core needle biopsy. This report provides a brief description of the clinical, laboratory, and imaging findings in this case of ECD. This diagnosis, albeit rare, should be taken into consideration in the context of incidental findings of abdominal tumors to ensure that treatment, when required, is instituted early.
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Affiliation(s)
- Juliano Cordova Vargas
- Hematology Department, Americas Oncologia e Hematologia, São Paulo, SP, Brazil
- Hematology Department, Hospital Samaritano Higienópolis, São Paulo, SP, Brazil
- Hematology Department, Hospital Metropolitano da Lapa, São Paulo, SP, Brazil
- School of Medicine, Centro Universitário São Camilo, São Paulo, SP, Brazil
| | - Caio Cardozo
- School of Medicine, Centro Universitário São Camilo, São Paulo, SP, Brazil
| | - Renata Stanzione
- Hematology Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Lucas Fiore
- Radiology Department, Hospital Metropolitano da Lapa, São Paulo, SP, Brazil
- Radiology Department, Hospital Samaritano Higienópolis, São Paulo, SP, Brazil
| | | | | | - Nelson Hamerschlak
- Hematology Department, Americas Oncologia e Hematologia, São Paulo, SP, Brazil
- Hematology Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
| | - Guilherme Perini
- Hematology Department, Americas Oncologia e Hematologia, São Paulo, SP, Brazil
- Hematology Department, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil
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Alarcon-Calderon A, Vassallo R, Yi ES, Ryu JH. Smoking-Related Interstitial Lung Diseases. Immunol Allergy Clin North Am 2023; 43:273-287. [PMID: 37055089 DOI: 10.1016/j.iac.2023.01.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
Abstract
Smoking-related interstitial lung diseases (ILDs) are a group of heterogeneous, diffuse pulmonary parenchymal disease processes associated with tobacco exposure. These disorders include pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia, acute eosinophilic pneumonia, and combined pulmonary fibrosis and emphysema. This review summarizes the current evidence of pathogenesis, clinical manifestations, diagnostic approach, prognosis, and treatment modalities for these diseases. We also discuss the interstitial lung abnormalities incidentally detected in radiologic studies and smoking-related fibrosis identified on lung biopsies.
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Affiliation(s)
- Amarilys Alarcon-Calderon
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, 200 1st Street, Southwest, Rochester, MN 55905, USA
| | - Robert Vassallo
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, 200 1st Street, Southwest, Rochester, MN 55905, USA
| | - Eunhee S Yi
- Department of Laboratory Medicine & Pathology, Mayo Clinic College of Medicine and Science, 200 1st Street, Southwest, Rochester, MN 55905, USA
| | - Jay H Ryu
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine and Science, 200 1st Street, Southwest, Rochester, MN 55905, USA.
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11
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Langerhans Cell Histiocytosis-Associated Pulmonary Adenocarcinoma: A Word of Caution during Molecular Determinations. JOURNAL OF MOLECULAR PATHOLOGY 2022. [DOI: 10.3390/jmp3040024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Background: Smoking habit is a common cause of pulmonary Langerhans cell histiocytosis (PLCH) and lung cancer and both diseases may coexist in the lung and share genetic alterations, such as V600E BRAF mutations. We collected a small series of three cases of PLCH-associated lung adenocarcinoma in order to evaluate the molecular setup in both components and underline the critical role of careful tissue selection for predictive molecular driver testing. Methods: Three cases of PLCH-associated adenocarcinoma were collected from consultation files. Clinical data from referring physicians and clinical data were obtained. The surgical biopsies were tested by immunohistochemistry and molecular analysis after separate dissection of adenocarcinoma cells and Langerhans histiocytes. Results: There were three active smoking men with a median age at diagnosis of 60.6 years. PLCH was disclosed at imaging during work-up for suspected lung cancer. Molecular analysis revealed KRAS (G12C and G13C) mutations in two cases and V600E BRAF mutation in one case of PLCH. Immunostaining with the V600E BRAF mutation specific primary antibody VE1 correctly recognized BRAF-mutated LCH. One case was wild-type in both diseases. Two similar cases were found in the literature, one of which showed a discrepant KRAS (G12D) mutation in adenocarcinoma and a V600E BRAF mutation in LCH; Conclusions: This case series of PLCH-associated adenocarcinoma underline the possibility to disclose identical genetic alterations in co-existing benign and malignant pathologies, then potentially creating erroneous interpretation of molecular analysis leading to inadequate therapeutic options in case of incorrect diagnostic recognition and inappropriate selection of both components through microdissection.
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12
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Potapenko VG, Baykov VV, Zinchenko AV, Potikhonova NA. Langerhans cell histiocytosis in adults: literature review. ONCOHEMATOLOGY 2022. [DOI: 10.17650/1818-8346-2022-17-4-16-32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Langerhans cells histiocytosis is a variant of malignant histiocytosis. The course and symptoms vary. patients with localized forms have a better prognosis, because local therapy is effective. patients with multifocal forms of histiocytosis receive systemic drug therapy, which cures some of the patients. This review provides up-to-date data about typical presentation of the organ involvement, diagnosis, course and therapy of various forms of Langerhans cells histiocytosis.
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Affiliation(s)
| | - V. V. Baykov
- I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia
| | - A. V. Zinchenko
- I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia
| | - N. A. Potikhonova
- Russian Research Institute of Hematology and Transfusiology, Federal Medical and Biological Agency
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13
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Phan DAT, Phung GB, Duong TT, Hoang AV, Ngo QD, Trinh DTN, Tran TT. The Value of BRAF VE1 Immunoexpression in Pediatric Langerhans Cell Histiocytosis. Fetal Pediatr Pathol 2022; 41:558-567. [PMID: 33295826 DOI: 10.1080/15513815.2020.1857483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
IntroductionVE1 is a monoclonal antibody detecting mutant BRAF V600E protein by immunohistochemistry (IHC) with a high concordance rate with molecular analysis in many cancers. Materials and methods: BRAF V600E mutation was assessed on 94 pediatric LCH patients using sequencing analysis and VE1 immunohistochemistry with stringent and lenient-scoring criteria. Results: BRAF V600E mutation exon 15 was detected by sequencing in 47.9% of LCH cases. BRAF V600E mutation rate in multiple-system LCH was 65.2%, significantly higher than in single-system LCH (p = .001). VE1 assays showed 35.6% sensitivity, 75.5% specificity (Stringent criteria), and 91.1% sensitivity, 35.7% specificity (Lenient criteria). Conclusions: The proportion of BRAF V600E mutational status was relatively high and related to high-risk LCH. Molecular assays for BRAF mutation detection are preferred in LCH lesions. VE1 is not ready as an alternative option for LCH BRAF testing.
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Affiliation(s)
- Dang Anh Thu Phan
- Pathology Department, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
| | - Gia Bao Phung
- Pathology Department, City Children Hospital- Ho Chi Minh City, Viet Nam
| | - Thanh Tu Duong
- Pathology Department, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
| | - Anh Vu Hoang
- Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
| | - Quoc Dat Ngo
- Pathology Department, University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
| | | | - Thanh Tung Tran
- Pathology Department, Children's Hospital 1- Ho Chi Minh City, Viet Nam
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14
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MUM1/IRF4 is Highly Expressed in Dermatopathic Lymphadenopathy: Potential Utility in Diagnosis and Differential Diagnosis. Am J Surg Pathol 2022; 46:1514-1523. [PMID: 35877199 DOI: 10.1097/pas.0000000000001935] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Dermatopathic lymphadenopathy (DL) is a distinctive type of lymph node hyperplasia that typically occurs in the setting of chronic dermatologic diseases. DL generally self-resolves following disappearance of the underlying skin stimulus and does not require any specific therapy. We recently observed multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) expression in a case of DL using immunohistochemical methods. The goal of this study was to systematically assess DL cases for MUM1/IRF4 expression and to survey other histiocytic and Langerhans cell lesions. We particularly focused on Langerhans cell histiocytosis (LCH) because the differential diagnosis of DL versus LCH in lymph nodes can be challenging. We identified high expression of MUM1/IRF4 in all 22 cases of DL tested. Specifically, MUM1/IRF4+ dendritic cells comprised 50% to 90% (median, 80%) of all dendritic cells in the paracortex of dermatopathic lymph nodes, always showing moderate or strong intensity. Among 10 DL cases stained for MUM1/IRF4 and langerin/CD207 using dual immunohistochemistry, MUM1/IRF4+ and langerin+ Langerhans cells represented 5% to 60% (median, 30%) of paracortical dendritic cells. MUM1/IRF4 was also positive in reactive Langerhans cells in skin biopsy specimens of all cases of spongiotic dermatitis (n=10) and normal skin (n=15), and was negative in all cases of LCH (n=24), Rosai-Dorfman disease (n=10), follicular dendritic cell sarcoma (n=5) and histiocytic sarcoma (n=4). In aggregate, our findings support the utility of MUM1/IRF4 to highlight the dendritic cells of DL and to distinguish DL from other histiocytic and Langerhans cells lesions.
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15
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Gencer A, Ozcibik G, Karakas FG, Sarbay I, Batur S, Borekci S, Turna A. Two smoking-related lesions in the same pulmonary lobe of squamous cell carcinoma and pulmonary Langerhans cell histiocytosis: A case report. World J Clin Cases 2022; 10:6722-6727. [PMID: 35979280 PMCID: PMC9294916 DOI: 10.12998/wjcc.v10.i19.6722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/14/2022] [Accepted: 04/24/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease usually affecting young adults. It is predicted that PLCH is a lung tumor precursor associated with dysfunction of the myeloid dendritic cells in the lung.
CASE SUMMARY A 70-year-old male patient presented with chronic cough and sputum. He had symptoms for 5 years and described shortness of breath on exertion for the previous 3 years. He had a 60 packs/year smoking history. Computerized tomography of the thorax revealed an 11-mm nodule in the right lung lower lobe superior segment and a 7-mm nodule in the right lung lower lobe poster basal segment. Those two nodules were resected by means of right thoracoscopic surgery. Pathological evaluation revealed a squamous cell carcinoma and PLCH.
CONCLUSION Coexistent squamous cell carcinoma and PLCH suggest possible association between PLCH and lung cancer.
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Affiliation(s)
- Aysegul Gencer
- Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty Campus, Istanbul 34098, Turkey
| | - Gizem Ozcibik
- Department of Thoracic Surgery, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
| | - Fatma Gulsum Karakas
- Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty Campus, Istanbul 34098, Turkey
| | - Ismail Sarbay
- Department of Thoracic Surgery, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
| | - Sebnem Batur
- Department of Pathology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
| | - Sermin Borekci
- Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty Campus, Istanbul 34098, Turkey
| | - Akif Turna
- Department of Thoracic Surgery, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul 34098, Turkey
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16
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Milman T, Eiger-Moscovich M, Henry RK, Ida CM, Ruben M, Shields CL, Lally SE, Penne RB, Stefanyszyn MA, Bilyk JR, Rapuano CJ, Rabinowitz M, Eagle RC. Cyclin D1 expression and molecular genetic findings in periocular histiocytoses and neoplasms of macrophage-dendritic cell lineage. Am J Ophthalmol 2022; 242:36-51. [PMID: 35594918 DOI: 10.1016/j.ajo.2022.05.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 05/06/2022] [Accepted: 05/13/2022] [Indexed: 11/19/2022]
Abstract
PURPOSE Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates Cyclin D1. The goal of this study was to determine whether Cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis. DESIGN Retrospective observational case series. METHODS Pathology records were searched for all patients with histiocytoses diagnosed between 1995-2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR). RESULTS There were 36 patients, 15 (42%) males and 21 (58%) females, with histiocytoses: 9 (25%) juvenile xanthogranuloma, 8 (22%) adult-onset asthma and periocular xanthogranuloma, 7 (19%) Langerhans cell histiocytosis, 5 (14%) Rosai-Dorfman disease, 5 (14%) xanthogranuloma not otherwise specified, 1 (3%) Erdheim-Chester disease, and 1 (3%) histiocytic sarcoma. Moderate-to-strong nuclear Cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR. CONCLUSIONS Our study confirms that the Cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.
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Affiliation(s)
- Tatyana Milman
- From the Department of Pathology (T.M., M.E.-M., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
| | - Maya Eiger-Moscovich
- From the Department of Pathology (T.M., M.E.-M., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Maya Eiger-Moscovich is currently practicing at Department of Ophthalmology, Hadassah Medical Center, Jerusalem, Israel. Meghan Ruben is currently practicing at Department of Ophthalmology, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Roger K Henry
- Institute of Ophthalmology and Visual Science, Rutgers-New Jersey Medical School at Rutgers University (R.K.H.), Newark, New Jersey
| | - Cristiane M Ida
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Mayo Clinic College of Medicine and Science (C.M.I.), Rochester, Minnesota; USA
| | - Megan Ruben
- Ocular Oncology Service (M.Ru., C.L.S., S.E.L., R.B.P.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Carol L Shields
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Ocular Oncology Service (M.Ru., C.L.S., S.E.L., R.B.P.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Sara E Lally
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Ocular Oncology Service (M.Ru., C.L.S., S.E.L., R.B.P.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Robert B Penne
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Ocular Oncology Service (M.Ru., C.L.S., S.E.L., R.B.P.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Mary A Stefanyszyn
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Oculoplastic and Orbital Surgery (M.A.S., J.R.B., M.Ra.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jurij R Bilyk
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Oculoplastic and Orbital Surgery (M.A.S., J.R.B., M.Ra.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Christopher J Rapuano
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Cornea Service (C.J.R.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Michael Rabinowitz
- Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Oculoplastic and Orbital Surgery (M.A.S., J.R.B., M.Ra.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Ralph C Eagle
- From the Department of Pathology (T.M., M.E.-M., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
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17
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Goyal G, Tazi A, Go RS, Rech KL, Picarsic JL, Vassallo R, Young JR, Cox CW, Van Laar J, Hermiston ML, Cao XX, Makras P, Kaltsas G, Haroche J, Collin M, McClain KL, Diamond EL, Girschikofsky M. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood 2022; 139:2601-2621. [PMID: 35271698 PMCID: PMC11022927 DOI: 10.1182/blood.2021014343] [Citation(s) in RCA: 120] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 02/24/2022] [Indexed: 11/20/2022] Open
Abstract
Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary (smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.
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Affiliation(s)
- Gaurav Goyal
- Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, AL
| | - Abdellatif Tazi
- Université de Paris, INSERM UMR 976, Saint Louis Research Institute, Paris, France
- French National Reference Center for Histiocytoses, Department of Pulmonology, Saint-Louis Teaching Hospital, Assistance Publique-Hôpiaux de Paris, Paris, France
| | | | - Karen L. Rech
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Jennifer L. Picarsic
- Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
| | | | | | | | - Jan Van Laar
- Department of Internal Medicine
- Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Michelle L. Hermiston
- Division of Pediatric Hematology-Oncology, University of California, San Francisco, San Francisco, CA
| | - Xin-Xin Cao
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Polyzois Makras
- LCH Adult Clinic
- Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, Athens, Greece
| | - Gregory Kaltsas
- 1st Propaedeutic Department of Internal Medicine, National and Kapodistrian University of Athens, Greece
| | - Julien Haroche
- Service de médecine interne 2, Centre de Référence des Histiocytoses, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris (APHP), Sorbonne Université, Paris, France
| | - Matthew Collin
- Newcastle University and Newcastle Upon Tyne Hospitals, Newcastle Upon Tyne, United Kingdom
| | - Kenneth L. McClain
- Texas Children's Cancer and Hematology Centers, Department of Pediatrics, Baylor College of Medicine, Houston, TX
| | - Eli L. Diamond
- Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Michael Girschikofsky
- Internal Medicine I (Hemostasis, Hematology and Stem, Cell Transplantation and Medical Oncology), Ordensklinikum Linz Elisabethinen, Linz, Austria
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18
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Elia D, Torre O, Vasco C, Geginat J, Abrignani S, Bulgheroni E, Carelli E, Cassandro R, Pacheco-Rodriguez G, Steagall WK, Moss J, Harari S. Pulmonary Langerhans cell histiocystosis (PLCH) and lymphangioleiomyomatosis (LAM) have circulating cells with loss of heterozygosity of the TSC2 gene. Chest 2022; 162:385-393. [PMID: 35231481 PMCID: PMC9470734 DOI: 10.1016/j.chest.2022.02.032] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/31/2022] [Accepted: 02/11/2022] [Indexed: 12/08/2022] Open
Abstract
BACKGROUND Lymphangioleiomyomatosis (LAM) and pulmonary Langerhans Cell Histiocytosis (PLCH) are cystic lung diseases in which a neoplastic cell is believed to be responsible for disease pathogenesis. The neoplastic LAM cell has mutations in the Tuberous Sclerosis Complex (TSC) genes, TSC1 or TSC2, whereas the neoplastic PLCH cell may have mutations in several genes, e.g., BRAF, NRAS, MAP2K1. These mutations are not specific for PLCH and they have been described in multiple cancers. TSC1 or TSC2 mutations and loss of heterozygosity (LOH) have also been described in cancers. RESEARCH QUESTION Is TSC2 LOH specific to LAM or is it also found in PLCH too? STUDY DESIGN We recruited LAM patients (53) and Healthy Volunteers (22) and compared the presence of cells with TSC2 LOH with PLCH patients (12). Blood and urine samples were collected for analysis. METHODS Fluorescence-activated cell sorting (FACS) was used to identify subpopulations of cells from blood and urine samples. We isolated CD45-CD235a-, CD45-CD235a+, CD45+CD235a- cells from blood following density gradient separation. Cells were screened for TSC2 LOH at 5 microsatellites markers (i.e., kg8, D16S3395, D16S3024, D16S521, D16S291). We obtained four cell subpopulations from urine (i.e., CD44v6+CD9+; CD44v6+CD9-; CD44v6-CD9+; CD44v6-CD9). RESULTS Using FACS, cells were isolated from blood and urine from PLCH patients that showed TSC2 LOH. Healthy volunteers did not have cells with TSC2 LOH. As a control, cells isolated from blood and urine from LAM patients gave results similar to those reported previously. These data show that TSC2 LOH is found in patients with cystic lung diseases with potential neoplastic characteristics, as well as in patients with cancer. INTERPRETATION The presence of TSC2 LOH in circulating cells is not specific for LAM. The data suggest that chromosomal abnormalities affecting the TSC2 gene are found in other diseases associated with cells having cancer-like neoplastic cells.
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Affiliation(s)
- Davide Elia
- Division of Pulmonary and Critical Care Medicine, San Giuseppe Hospital MultiMedica IRCCS, Milan, Italy
| | - Olga Torre
- Division of Pulmonary and Critical Care Medicine, San Giuseppe Hospital MultiMedica IRCCS, Milan, Italy
| | - Chiara Vasco
- Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Jens Geginat
- Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Department of Medicine, Ospedale San Giuseppe MultiMedica IRCCS, Milan, Italy
| | - Sergio Abrignani
- Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Department of Medicine, Ospedale San Giuseppe MultiMedica IRCCS, Milan, Italy
| | - Elisabetta Bulgheroni
- Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Elena Carelli
- Istituto Nazionale di Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy
| | - Roberto Cassandro
- Division of Pulmonary and Critical Care Medicine, San Giuseppe Hospital MultiMedica IRCCS, Milan, Italy
| | - Gustavo Pacheco-Rodriguez
- Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Wendy K Steagall
- Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Joel Moss
- Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
| | - Sergio Harari
- Division of Pulmonary and Critical Care Medicine, San Giuseppe Hospital MultiMedica IRCCS, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; Department of Medicine, Ospedale San Giuseppe MultiMedica IRCCS, Milan, Italy
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19
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Machado I, Alcacer Fernández-Coronado J, Requena C, Través V, Latorre Martínez N, Ortega J, Requena L, Alcacer García J. [Cutaneous Rosai-Dorfman disease with lack of BRAF-V600, KRAS or NRAS mutations: A reactive or neoplastic disorder?]. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2022; 55:52-56. [PMID: 34980442 DOI: 10.1016/j.patol.2019.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/21/2019] [Accepted: 03/24/2019] [Indexed: 06/14/2023]
Abstract
Non-Langerhans cell histiocytosis, including Rosai-Dorfman disease (RDD) and xanthogranuloma are rare disorders with occasional overlapping in the histopathological and immunohistochemical (IHC) findings. We report the case of a 53-year-old woman with erythematous-violaceous plaques on the cheeks and edema in the auricular pavilions. A biopsy was performed and the histopathological examination revealed a histiocytic proliferation with emperipolesis characteristic of RDD and lymphoplasmocitic infiltrate. IHC analysis showed S100 and CD68 positivity in the histiocytes but was negative for CD1a, supporting the diagnosis of RDD. Molecular analysis failed to detect BRAF-V600, NRAS or KRAS mutation. We discuss the differential diagnosis of cutaneous non-Langerhans cell histiocytosis. Pathologist must be aware of unusual presentations of RDD and further treatment options must be explored for patients with unresectable lesions and/or resistance to the classical management of RDD.
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Affiliation(s)
- Isidro Machado
- Departamento de Patología, Instituto Valenciano de Oncología, Valencia, España; Laboratorio Patologika, Hospital Quirón, Valencia, España.
| | | | - Celia Requena
- Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, España
| | - Victor Través
- Departamento de Patología, Instituto Valenciano de Oncología, Valencia, España
| | | | - José Ortega
- Departamento de Patología, Hospital Quirón Torrevieja, Torrevieja, Alicante, España
| | - Luis Requena
- Servicio de Dermatología, Hospital Universitario Fundación Jiménez Díaz, Madrid, España
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20
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Hazim AZ, Ruan GJ, Hu M, Ravindran A, Rech KL, Young JR, Cox CW, Abeykoon JP, Scheckel C, Vassallo R, Ryu JH, Tobin WO, Koster MJ, Bennani NN, Shah MV, Goyal G, Go RS. Langerhans cell histiocytosis with lung involvement in isolation and multisystem disease: Staging, natural history, and comparative survival. Am J Hematol 2021; 96:1604-1610. [PMID: 34553412 DOI: 10.1002/ajh.26355] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/14/2021] [Accepted: 09/20/2021] [Indexed: 01/20/2023]
Abstract
Langerhans cell histiocytosis (LCH) is a histiocytic neoplasm that can involve the lungs as single system (LCH-SSL) or multisystem disease (LCH-MSL). The role of full-body radiographic staging to determine whether patients have LCH-SSL or LCH-MSL is unclear. Long-term outcomes of LCH-SSL versus LCH-MSL and multisystem without lung involvement (LCH-MSNL) are unknown. A retrospective study of adult LCH patients seen at our center from January 2000 to 2020 was performed. In Part 1, we addressed utility of whole-body staging imaging among those presenting with isolated pulmonary signs or symptoms. Staging was defined as fluorodeoxyglucose positron emission tomography-computed tomography (CT) or whole-body CT obtained within 3 months of diagnosis. In Part 2, we examined the frequency of developing extra-pulmonary disease over time and mortality in patients with LCH-SSL. In Part 3, we compared the overall survival of LCH-SSL, LCH-MSL, and LCH-MSNL. Part 1: 240 patients with LCH were identified. A total of 112 (47%) had pulmonary signs or symptoms at presentation. Thirty-four (30%) underwent radiographic staging and only one showed evidence of extra-pulmonary disease. Part 2: 108 (45%) were LCH-SSL. Median follow-up duration of 4.5 years (95% confidence interval [CI]: 2.9-6.0). None developed extra-pulmonary disease. Part 3: 5-year survival: 94% (95% CI: 84%-98%) for LCH-SSL, 78% (95% CI: 59%-90%) for LCH-MSL, and 75% (95% CI: 53%-89%) for LCH-MSNL. LCH patients presenting with isolated pulmonary signs or symptoms rarely have extra-pulmonary involvement at the time of diagnosis and generally do not develop extra-pulmonary progression. LCH-SSL has the best overall survival, while LCH-MSL and LCH-MSNL have similar clinical outcomes.
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Affiliation(s)
| | - Gordon J. Ruan
- Division of Hematology Mayo Clinic Rochester Minnesota USA
| | - Marie Hu
- Division of Hematology‐Oncology University of Minnesota Minneapolis Minnesota USA
| | - Aishwarya Ravindran
- Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
| | - Karen L. Rech
- Department of Laboratory Medicine and Pathology Mayo Clinic Rochester Minnesota USA
| | - Jason R. Young
- Department of Radiology Mayo Clinic Rochester Minnesota USA
| | | | | | - Caleb Scheckel
- Division of Hematology Mayo Clinic Rochester Minnesota USA
| | - Robert Vassallo
- Division of Pulmonary and Critical Care Medicine Mayo Clinic Rochester Minnesota USA
| | - Jay H. Ryu
- Division of Pulmonary and Critical Care Medicine Mayo Clinic Rochester Minnesota USA
| | | | | | | | - Mithun V. Shah
- Division of Hematology Mayo Clinic Rochester Minnesota USA
| | - Gaurav Goyal
- Division of Hematology‐Oncology University of Alabama at Birmingham Birmingham Alabama USA
- Research Collaborator (limited‐tenure), Mayo Clinic Rochester Minnesota USA
| | - Ronald S. Go
- Division of Hematology Mayo Clinic Rochester Minnesota USA
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21
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Rech KL, He R. Challenges in the Histopathologic Diagnosis of Histiocytic Neoplasms. J Natl Compr Canc Netw 2021; 19:1305-1311. [PMID: 34781270 DOI: 10.6004/jnccn.2021.7098] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 09/28/2021] [Indexed: 11/17/2022]
Abstract
Histiocytic neoplasms, including Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD), present a diagnostic challenge due to nonspecific fibroinflammatory infiltrates and a diverse clinical presentation. The pathologist can play a key role in classification of these disorders through multidisciplinary collaboration and correlation of pathologic features with clinical and radiologic findings. The histopathologic differential diagnosis is broad, requiring knowledge of the possible diagnoses at each specific anatomic site, and a careful assessment to exclude other inflammatory and neoplastic disorders. An immunohistochemistry panel including CD163, CD1a, langerin, S100, Factor XIIIa, OCT2, and BRAF V600E can provide definitive diagnosis in LCH and RDD, whereas ECD requires classic clinical features as well as confirmation of an activating MAPK pathway mutation by genetic studies.
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Affiliation(s)
- Karen L Rech
- Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
| | - Rong He
- Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota
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22
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The genomic landscape of lung adenocarcinoma—insights towards personalized medicine. PROCEEDINGS OF THE INDIAN NATIONAL SCIENCE ACADEMY 2021. [DOI: 10.1007/s43538-021-00054-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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23
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Urinary involvement in Erdheim-Chester disease: computed tomography imaging findings. Abdom Radiol (NY) 2021; 46:4324-4331. [PMID: 33970298 DOI: 10.1007/s00261-021-03106-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 04/20/2021] [Accepted: 04/24/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE To describe the urological manifestations of Erdheim-Chester disease (ECD) and their computed tomography (CT) findings. METHODS We retrospectively reviewed 48 patients diagnosed with ECD at Peking Union Medical College Hospital from January 2014 to January 2020. Twenty-four patients exhibited urological manifestations. Their CT findings, including appearances of the involved area (e.g., perirenal space, renal sinus, ureters, renal arteries, and adrenal glands), occurrence rate of ECD involvement in each area, signal enhancement pattern after CT contrast agent administration, disease progression, and causes of hydronephrosis were discussed. RESULTS In 24 patients with evidence of ECD urological involvement, the most common manifestation was perirenal infiltration, appearing as "hairy kidney" on unenhanced CT scans and moderate signal enhancement on enhanced CT scans (17/24, 70.8%). Other manifestations included renal sinus infiltration (16/24, 66.7%), proximal ureter involvement (14, 58.3%), renal artery sheath (10, 41.7%), hydronephrosis (14, 58.3%), and adrenal glands involvement (8, 33.3%). The histiocytic infiltrate was mostly bilateral, starting from the perirenal space and spreading to the renal sinus and ureters. Hydronephrosis was usually associated with infiltration of ureters. CONCLUSION Kidneys are the most common visceral organs affected by ECD. CT scanning is not only advantageous in early diagnosis, but also critical for designing the treatment regime for patients with ECD.
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24
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Maraqa B, Al-Ashhab M, Kamal N, El Khaldi M, Sughayer M. Concomitant Langerhans cell histiocytosis of cervical lymph nodes in adult patients with papillary thyroid carcinoma: A report of two cases and review of the literature. Autops Case Rep 2021. [PMID: 34307217 DOI: 10.4322/acr.2021.253.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Objective : Langerhans cell histiocytosis (LCH) is an uncommon entity of unknown etiology. It contains a wide range of clinical presentations. The discovery of oncogenic BRAF V600E mutation in LCH has provided additional evidence that LCH is a neoplasm. Papillary thyroid carcinoma is the most common cancer of the thyroid characterized by a high incidence of BRAF V600E mutations. LCH with concomitant PTC is rare, with few cases reported in the literature. Cases summary We identified two cases of LCH with concomitant papillary thyroid carcinoma in adult patients. The first was a 49-year-old female with a thyroid nodule diagnosed with papillary thyroid carcinoma. Later, the patient had a left neck mass; Ultrasound-guided lymph node FNA was diagnosed with Langerhans histiocytosis. Subsequently, a chest CT scan revealed signs of Langerhans cell histiocytosis in the lung. The second case refers to a 69-year-old male who presented with a left thyroid nodule diagnosed on FNA cytology as papillary thyroid carcinoma. The patient was found to have multiple bone lytic lesions. Biopsies revealed Langerhans cell histiocytosis. Later, the patient experienced LCH involvement of the bone marrow with associated secondary myelofibrosis. Conclusions LCH is rare in adults; the association with papillary thyroid carcinoma is reported and should be considered in the presence of Langerhans cell groups along with PTC, whether in the thyroid gland or cervical lymph nodes. Once LCH has been diagnosed, pulmonary involvement should also be investigated. This will direct treatment plans for patients with pulmonary or systemic disease involvement.
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Affiliation(s)
- Bayan Maraqa
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Maxim Al-Ashhab
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Nazmi Kamal
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Mousa El Khaldi
- King Hussein Cancer Center, Department of Radiology, Amman, Jordan
| | - Maher Sughayer
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
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25
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Feng S, Han L, Yue M, Zhong D, Cao J, Guo Y, Sun Y, Zhang H, Cao Z, Cui X, Liu R. Frequency detection of BRAF V600E mutation in a cohort of pediatric langerhans cell histiocytosis patients by next-generation sequencing. Orphanet J Rare Dis 2021; 16:272. [PMID: 34116682 PMCID: PMC8196454 DOI: 10.1186/s13023-021-01912-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 06/07/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Langerhans cell histiocytosis (LCH) is a rare neoplastic disease that occurs in both children and adults, and BRAF V600E is detected in up to 64% of the patients. Several studies have discussed the associations between BRAF V600E mutation and clinicopathological manifestations, but no clear conclusions have been drawn regarding the clinical significance of the mutation in pediatric patients. RESULTS We retrieved the clinical information for 148 pediatric LCH patients and investigated the BRAF V600E mutation using next-generation sequencing alone or with droplet digital PCR. The overall positive rate of BRAF V600E was 60/148 (41%). The type of sample (peripheral blood and formalin-fixed paraffin-embedded tissue) used for testing was significantly associated with the BRAF V600E mutation status (p-value = 0.000 and 0.000). The risk of recurrence declined in patients who received targeted therapy (p-value = 0.006; hazard ratio 0.164, 95%CI: 0.046 to 0.583). However, no correlation was found between the BRAF V600E status and gender, age, stage, specific organ affected, TP53 mutation status, masses close to the lesion or recurrence. CONCLUSIONS This is the largest pediatric LCH study conducted with a Chinese population to date. BRAF V600E in LCH may occur less in East Asian populations than in other ethnic groups, regardless of age. Biopsy tissue is a more sensitive sample for BRAF mutation screening because not all of circulating DNA is tumoral. Approaches with low limit of detection or high sensitivity are recommended for mutation screening to avoid type I and II errors.
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Affiliation(s)
- Shunqiao Feng
- Department of Hematology, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China
| | - Lin Han
- Running Gene Inc, Beijing, China
| | - Mei Yue
- Department of Hematology, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China
| | - Dixiao Zhong
- Department of Hematology, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China
| | - Jing Cao
- Department of Hematology, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China
| | | | | | | | | | - Xiaodai Cui
- Department of Key Laboratory, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China.
| | - Rong Liu
- Department of Hematology, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100020, China.
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26
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Si YC, Liu Q, Hou HJ, Huang P. Multifocal eosinophilic granuloma of the jaws with long-term follow-up: a case report. HUA XI KOU QIANG YI XUE ZA ZHI = HUAXI KOUQIANG YIXUE ZAZHI = WEST CHINA JOURNAL OF STOMATOLOGY 2021; 39:355-361. [PMID: 34041887 PMCID: PMC8218260 DOI: 10.7518/hxkq.2021.03.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 04/09/2021] [Indexed: 02/08/2023]
Abstract
Eosinophilic granuloma, a rare disease, has various clinical manifestations and no specific X-rays features and is thus easily misdiagnosed. This paper reports a case of multifocal eosinophilic granuloma of jaw with long-term follow-up. The patient initially presented with periodontal tissue destruction.The diagnosis, treatment and prognosis of multifocal eosinophilic granuloma of jaw were discussed in combination with the literature to alert this disease in clinical practice.
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Affiliation(s)
- Yu-Chen Si
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Qian Liu
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Hai-Juan Hou
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
| | - Ping Huang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
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27
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Feng C, Li Y, Ke H, Peng X, Guo H, Zhan L, Xiong X, Weng W, Li J, Fang J. Immune Microenvironment in Langerhans Cell Histiocytosis: Potential Prognostic Indicators. Front Oncol 2021; 11:631682. [PMID: 34026610 PMCID: PMC8138578 DOI: 10.3389/fonc.2021.631682] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/13/2021] [Indexed: 01/18/2023] Open
Abstract
In this study, the immune microenvironment in Langerhans cell histiocytosis (LCH) was characterized to determine if immune indices are predictive of severity. Serum samples from 54 treatment-naïve patients were analyzed quantitatively for inflammatory cytokines and immunoglobulins before and after the induction of chemotherapy. The initial serum sIL-2R, TNF-α, and IL-10 of untreated LCH patients with risk organ involvement (RO+) were significantly higher than those with single-system (SS) involvement. LCH patients with hematologic involvement exhibited a significantly higher sIL-2R, TNF-α, IL-10, and IL-1β expression, as compared to the group without involvement. sIL-2R, TNF-α, and IL-10 were increased in patients with liver or spleen involvement. Th cells have decreased in the liver+ and spleen+ group, and Ts cells were significantly decreased in non-response group after induction chemotherapy. The serum level of immune indices represents, to some extent, the severity of the disease. Pertinent laboratory inspections can be used to improve risk stratification and guide immunotherapy.
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Affiliation(s)
- Chuchu Feng
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yang Li
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Huang Ke
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiaomin Peng
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Haixia Guo
- Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liping Zhan
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xilin Xiong
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Wenjun Weng
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jiaqiang Li
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Jianpei Fang
- Department of Pediatric Hematology/Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
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28
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NRAS Mutations May Be Involved in the Pathogenesis of Cutaneous Rosai Dorfman Disease: A Pilot Study. BIOLOGY 2021; 10:biology10050396. [PMID: 34063325 PMCID: PMC8147632 DOI: 10.3390/biology10050396] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 04/26/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023]
Abstract
Background: Purely cutaneous Rosai-Dorfman disease (RDD) is a rare histiocytic proliferative disorder limited to the skin. To date, its pathogenesis remains unclear. Owing to recent findings of specific mutations in the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway in histiocytic proliferative disorders, it provides a novel perspective on the pathomechanism of cutaneous RDD. We aim to investigate the genomic mutations in MAPK/ERK pathway in cutaneous RDD. Methods: We retrospectively recruited all cases of cutaneous RDD from two hospitals in Taiwan from January 2010 to March 2020 with the clinicopathologic features, immunohistochemistry, and treatment. Mutations of neuroblastoma RAS viral oncogene homolog (NRAS), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in MAPK/ERK pathway were investigated by the highly sensitive polymerase chain reaction with Sanger sequencing. Results: Seven patients with cutaneous RDD were recruited with nine biopsy specimens. The median age was 46 years (range: 17–62 years). Four of seven patients (57.1%) received tumor excision, while the other three chose oral and/or topical or intralesional steroids. NRAS mutation was detected in 4 of 7 cases (4/7; 51.7%), and NRAS A146T was the most common mutant point (n = 4/7), followed by NRAS G13S (n = 2/7). There is no KRAS or BRAF mutation detected. Conclusions: We report the NRAS mutation is common in cutaneous RDD, and NRAS A146T was the most frequent mutation in this cohort. Mutations in the NRAS gene can activate the RAS/MAPK signaling and have been reported to be associated with various cancers. It indicates that NRAS mutation in MAPK/ERK pathway may involve the pathogenesis of cutaneous RDD.
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29
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Machado I, Columbie A, Nieto Morales G, Forteza-Suarez M, Renó Céspedes JDLS, Marhuenda Fluixa A, Llombart-Bosch A. [Bone and soft tissue Langerhans cell histiocytosis with multinucleated giant cells and BRAF V600E mutation]. REVISTA ESPANOLA DE PATOLOGIA : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ANATOMIA PATOLOGICA Y DE LA SOCIEDAD ESPANOLA DE CITOLOGIA 2021; 54:136-140. [PMID: 33726891 DOI: 10.1016/j.patol.2018.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 07/21/2018] [Accepted: 08/15/2018] [Indexed: 10/28/2022]
Abstract
Langerhans cell histiocytosis (LCH) is a heterogeneous disease characterized by proliferation of Langerhans cells and BRAF mutation in almost half of the cases. Bone involvement is common but large soft tissue disease is uncommon. We report a pediatric patient with a large tumor mass involving the left iliac bone and the adjacent soft tissue. The computed tomography scan showed an osteolytic lesion with soft tissue extension. Surgical curettage of the lesion was performed and the final histopathologic diagnosis was LCH with CD1a immunoreactivity in tumor cells. The molecular analysis revealed a BRAF V600E mutation. We discuss the histopathological and immunohistochemical differential diagnosis with histiocytosis other than LCH.
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Affiliation(s)
- Isidro Machado
- Departamento de Patología, Instituto Valenciano de Oncología, Valencia, España.
| | - Ariel Columbie
- Departamento de Patología, Instituto Nacional de Oncología y Radiobiología (INOR), La Habana, Cuba
| | - Gema Nieto Morales
- Laboratorio de Biología Molecular, Departamento de Patología, Universidad de Valencia, Valencia, España
| | - Mariuska Forteza-Suarez
- Servicio de Oncología Pediátrica, Instituto Nacional de Oncología y Radiobiología (INOR), La Habana, Cuba
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30
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Maraqa B, Al-Ashhab M, Kamal N, El Khaldi M, Sughayer M. Concomitant Langerhans cell histiocytosis of cervical lymph nodes in adult patients with papillary thyroid carcinoma: A report of two cases and review of the literature. AUTOPSY AND CASE REPORTS 2021; 11:e2021253. [PMID: 34307217 PMCID: PMC8214889 DOI: 10.4322/acr.2021.253] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 01/21/2021] [Indexed: 12/13/2022] Open
Abstract
Objective : Langerhans cell histiocytosis (LCH) is an uncommon entity of unknown etiology. It contains a wide range of clinical presentations. The discovery of oncogenic BRAF V600E mutation in LCH has provided additional evidence that LCH is a neoplasm. Papillary thyroid carcinoma is the most common cancer of the thyroid characterized by a high incidence of BRAF V600E mutations. LCH with concomitant PTC is rare, with few cases reported in the literature. Cases summary We identified two cases of LCH with concomitant papillary thyroid carcinoma in adult patients. The first was a 49-year-old female with a thyroid nodule diagnosed with papillary thyroid carcinoma. Later, the patient had a left neck mass; Ultrasound-guided lymph node FNA was diagnosed with Langerhans histiocytosis. Subsequently, a chest CT scan revealed signs of Langerhans cell histiocytosis in the lung. The second case refers to a 69-year-old male who presented with a left thyroid nodule diagnosed on FNA cytology as papillary thyroid carcinoma. The patient was found to have multiple bone lytic lesions. Biopsies revealed Langerhans cell histiocytosis. Later, the patient experienced LCH involvement of the bone marrow with associated secondary myelofibrosis. Conclusions LCH is rare in adults; the association with papillary thyroid carcinoma is reported and should be considered in the presence of Langerhans cell groups along with PTC, whether in the thyroid gland or cervical lymph nodes. Once LCH has been diagnosed, pulmonary involvement should also be investigated. This will direct treatment plans for patients with pulmonary or systemic disease involvement.
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Affiliation(s)
- Bayan Maraqa
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Maxim Al-Ashhab
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Nazmi Kamal
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
| | - Mousa El Khaldi
- King Hussein Cancer Center, Department of Radiology, Amman, Jordan
| | - Maher Sughayer
- King Hussein Cancer Center, Department of Pathology and Laboratory Medicine, Amman, Jordan
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Radzikowska E. Update on Pulmonary Langerhans Cell Histiocytosis. Front Med (Lausanne) 2021; 7:582581. [PMID: 33763431 PMCID: PMC7982411 DOI: 10.3389/fmed.2020.582581] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Accepted: 12/21/2020] [Indexed: 12/14/2022] Open
Abstract
Pulmonary Langerhans cell (LC) histiocytosis (PLCH) has unknown cause and is a rare neoplastic disorder characterized by the infiltration of lungs and various organs by bone marrow-derived Langerhans cells with an accompanying strong inflammatory response. These cells carry somatic mutations of BRAF gene and/or NRAS, KRAS, and MAP2K1 genes, which cause activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. PLCH occurs predominantly in young smokers, without gender predominance. Lungs might be involved as an isolated organ or as part of a multiorgan disease. High-resolution computed chest tomography plays an outstanding role in PLCH diagnosis. The typical radiological picture of PLCH is the presence of small intralobular nodules, “tree in bud” opacities, cavitated nodules, and thin- and thick-walled cysts, frequently confluent. Histological examination of the lesion and demonstration of characteristic eosinophilic granulomas with the presence of LCs that display antigen CD1a or CD207 in immunohistochemistry are required for definite diagnosis. Smoking cessation is the most important recommendation for PLCH patients, but treatment of progressive PLCH and multisystem disease is based on chemotherapy. Recently, new targeted therapies have been implemented.
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Affiliation(s)
- Elzbieta Radzikowska
- III Department of Lung Diseases and Oncology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland
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32
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Wang J, Xie L, Miao Y, Liu X, Tang Y, Xi Y, Chang J, Wu Y, Jiang L. Adult pulmonary Langerhans cell histiocytosis might consist of two distinct groups: isolated form and extrapulmonary recidivism type. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:357. [PMID: 33708984 PMCID: PMC7944282 DOI: 10.21037/atm-20-8141] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Background Adult pulmonary Langerhans cell histiocytosis (PLCH) is a rare form of Langerhans cell histiocytosis (LCH) that typically occurs in cigarette smokers. The clinical course of PLCH is unpredictable; the disease may resolve spontaneously, or lead to multi-organ failure and death. To better understand this idiopathic disease, we retrospectively overviewed a cohort of Asian patients with PLCHs. Methods Herein, we have provided detailed clinicopathological features and molecular findings of PLCHs in a Southwestern Chinese population, including the expressions of apoptotic protein P16, programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). Importantly, the BRAFV600E mutation was observed in this cohort. Results In accordance with the follow up data, the cohort was subdivided into two groups, an isolated pulmonary group and extrapulmonary recidivism group. Among the isolated group, the participants were predominantly young males (<40 years old), with a history of smoking, respiratory symptoms (cough and difficulty breathing), showed more cystic lesions in computed tomography (CT) scanning, had more cellular Langerhans granulomas under the microscope, overexpression of P16 (66.7%), high PD-1 (100%) and low PD-L1 (33.3%) expressions, and no BRAFV600E mutation was detected. In contrast, the extrapulmonary recidivism group showed significantly older age (>40 years old), recurrent spontaneous pneumothorax, more nodular changes in CT scanning, more interstitial fibrosis histologically, expression rates of 100% of P16, 66.7% of PD-1, and 33.3% of PD-L1; and importantly, BRAFV600E mutation was detected in 33.3% of this subdivision. Conclusions We found that adult PLCH might consist of two distinct groups: an isolated form and extrapulmonary recidivism PLCH. Overexpression of P16 could be a diagnostic biomarker for PLCH. An extremely low mutation rate of the BRAF gene in adult PLCH in our cohort indicated that there might be other pathogeneses for this disease among Asian patients.
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Affiliation(s)
- Jing Wang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.,Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
| | - Liwu Xie
- Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
| | - Yuchun Miao
- Department of Respiratory medicine, Shanxi Coal Central Hospital, Taiyuan, China
| | - Xiaoyu Liu
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Yuan Tang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Yanfeng Xi
- Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
| | - Jiang Chang
- Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
| | - Yueqin Wu
- Department of Pathology, Shanxi Tumor Hospital, Taiyuan, China
| | - Lili Jiang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
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Phan TDA, Phung BG, Duong TT, Hoang VA, Ngo DQ, Trinh NDT, Tran TT. A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children. J Pathol Transl Med 2021; 55:112-117. [PMID: 33494131 PMCID: PMC7987525 DOI: 10.4132/jptm.2020.11.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 11/30/2020] [Indexed: 11/21/2022] Open
Abstract
Background Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH. Methods We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF_V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed. Results BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF_V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression. Conclusions In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.
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Affiliation(s)
- Thu Dang Anh Phan
- Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Bao Gia Phung
- Department of Pathology, City Children Hospital, Ho Chi Minh City, Vietnam
| | - Tu Thanh Duong
- Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Vu Anh Hoang
- Center for Molecular Biomedicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Dat Quoc Ngo
- Department of Pathology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | | | - Tung Thanh Tran
- Department of Pathology, Children Hospital 1, Ho Chi Minh City, Vietnam
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Bugshan AS, Alsaati MA, Syed FA, Almulhim KS, Abdulhady AI. Incidental Diagnosis on Orthopantomography of Langerhans Cell Histiocytosis with Multifocal Jaw Involvement: A Case Report of Single-System Disease. AMERICAN JOURNAL OF CASE REPORTS 2020; 21:e928307. [PMID: 33232308 PMCID: PMC7701021 DOI: 10.12659/ajcr.928307] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Langerhans cell histiocytosis (LCH) is a relatively rare neoplasm with a strong inflammatory component. It has diverse clinical manifestations, which range from a single lesion or multiple bony lesions to severe multisystem involvement. Approximately 10% to 20% of cases of LCH occur in the jaw, with the posterior mandible being the site most frequently involved. CASE REPORT We report on the case of a 42-year-old man who presented with bilateral osteolytic lesions in the posterior mandible that were incidentally discovered during routine radiographic screening. Histological examination of the specimen confirmed the diagnosis of LCH. CONCLUSIONS This case illustrates the importance of orthopantomography (OPG) as a screening tool in new patients to perform an overall evaluation of the teeth and surrounding structures, such as the bone, temporomandibular joint, and sinuses. Moreover, OPG can be used to screen for the presence of asymptomatic lesions that are often diagnosed incidentally on radiographs.
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Affiliation(s)
- Amr S Bugshan
- Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed A Alsaati
- Department of Maxillofacial and Oral Health, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Faiyaz A Syed
- Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Khalid S Almulhim
- Department of Restorative Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Adel I Abdulhady
- Department of Biomedical Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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Initial presentation of Pulmonary Langerhans cell histiocytosis as recurrent spontaneous pneumothoraces. Respir Med Case Rep 2020; 31:101280. [PMID: 33209579 PMCID: PMC7658490 DOI: 10.1016/j.rmcr.2020.101280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 10/19/2020] [Accepted: 11/02/2020] [Indexed: 11/22/2022] Open
Abstract
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare cystic lung disease. The natural history is often unpredictable making it difficult to diagnose. We report a 63-year-old male with dyspnoea, chronic cough and recurrent respiratory tract infections, who developed progressive multifocal cystic lesions on pulmonary nodule surveillance over 4 years. He was a heavy smoker with a history of multiple spontaneous pneumothoraces in his teens. Extensive investigations culminated in a thoracoscopic wedge resection, which identified histiocytic nodules staining positive for CD1a and thus confirming the diagnosis of PLCH. It is now apparent that PLCH was the likely cause of his pneumothoraces.
PLCH is difficult to diagnose due to its heterogeneous presentation and insidious natural history. PLCH is a cause of recurrent pneumothoraces, and almost exclusively in smokers. PLCH usually has innumerable cystic lesions that progress in a nodulocystic pattern. CD1 antigen is characteristic of PLCH as it is uniquely expressed in Langerhans-like dendritic cells. Smoking cessation is an effective first line monotherapy for PLCH.
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Detection of BRAF V600E Mutation in Ganglioglioma and Pilocytic Astrocytoma by Immunohistochemistry and Real-Time PCR-Based Idylla Test. DISEASE MARKERS 2020; 2020:8880548. [PMID: 32879641 PMCID: PMC7448243 DOI: 10.1155/2020/8880548] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 06/21/2020] [Accepted: 07/31/2020] [Indexed: 11/17/2022]
Abstract
The BRAF V600E mutation is an important oncological target in certain central nervous system (CNS) tumors, for which a possible application of BRAF-targeted therapy grows continuously. In the present study, we aim to determine the prevalence of BRAF V600E mutations in a series of ganglioglioma (GG) and pilocytic astrocytoma (PA) cases. Simultaneously, we decided to verify whether the combination of fully automated tests—BRAF-VE1 immunohistochemistry (IHC) and Idylla BRAF mutation assay—may be useful to accurately predict it in the case of specified CNS tumors. The study included 49 formalin-fixed, paraffin-embedded tissues, of which 15 were GG and 34 PA. Immunohistochemistry with anti-BRAF V600E (VE1) antibody was performed on tissue sections using the VentanaBenchMark ULTRA platform. All positive or equivocal cases on IHC and selected negative ones were further assessed using the Idylla BRAF mutation assay coupled with the Idylla platform. The BRAF-VE1 IHC was positive in 6 (6/49; 12.3%) and negative in 39 samples (39/49; 79.6%). The interpretation of immunostaining results was complicated in 4 cases, of which 1 tested positive for the Idylla BRAF mutation assay. Therefore, the overall positivity rate was 14.3%. This included 2 cases of GG and 5 cases of PA. Our study found that BRAF V600E mutations are moderately frequent in PA and GG and that for these tumor entities, IHC VE1 is suitable for screening purposes, but all negative, equivocal, and weak positive cases should be further tested with molecular biology techniques, of which the Idylla system seems to be a promising tool.
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Kim HM, Yang WI, Lyu CJ, Hahn SM, Yoon SO. Descriptive Analysis of Histiocytic and Dendritic Cell Neoplasms: A Single-Institution Experience. Yonsei Med J 2020; 61:774-779. [PMID: 32882761 PMCID: PMC7471072 DOI: 10.3349/ymj.2020.61.9.774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Revised: 07/21/2020] [Accepted: 08/06/2020] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Histiocytic and dendritic cell neoplasms are rare hematologic tumors. This study aimed to describe the epidemiologic features of the entire spectrum of histiocytic and dendritic cell neoplasms, including clinicopathological variables and patient outcomes. MATERIALS AND METHODS We comprehensively reviewed 274 patients who were diagnosed with histiocytic and dendritic neoplasms at Severance Hospital, Seoul, South Korea between 1995 and 2018. RESULTS The most common neoplasm was Langerhans cell histiocytosis (LCH), followed by dermal xanthogranuloma. Among non-LCH sarcomas, histiocytic sarcoma (HS) showed a relatively high prevalence, followed by follicular dendritic cell sarcoma (FDCS). Disseminated juvenile xanthogranuloma (DJG), Erdheim-Chester disease (ECD), indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) rarely occurred. Generally, these tumors presented in childhood, although the non-LCH sarcoma (HS/FDCS/IDCS/IDCT) group of tumors and ECD occurred in late adulthood. Multiorgan involvement and advanced Ann-Arbor stage, as well as recurrence and death of disease, were not uncommon. The non-LCH sarcoma group had the worst overall survival, compared to the DJG, ECD, and LCH groups. CONCLUSION Our findings indicate that histiocytic and dendritic cell neoplasms exhibit heterogeneous epidemiologic characteristics and that some patients may have unfavorable outcomes, especially those with non-LCH sarcoma.
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Affiliation(s)
- Hye Min Kim
- Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Woo Ick Yang
- Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Chuhl Joo Lyu
- Department of Pediatrics, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Seung Min Hahn
- Department of Pediatrics, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea
| | - Sun Och Yoon
- Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
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The combination of methotrexate and cytosine arabinoside in newly diagnosed adult Langerhans cell histiocytosis: a prospective phase II interventional clinical trial. BMC Cancer 2020; 20:433. [PMID: 32423455 PMCID: PMC7236107 DOI: 10.1186/s12885-020-06872-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 04/15/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Langerhans Cell Histiocytosis (LCH) is a rare disease puzzling both children and adults, however outcome of adult patients is unfavorable. This prospective interventional trial aims to test the efficacy and safety of the combination of methotrexate and cytosine arabinoside in adult LCH patients. METHOD A total of 36 patients enrolled diagnosed with LCH and treated in our center from 1st Jan, 2014 to 30th Jun, 2016. RESULT Nineteen patients underwent the detection of BRAF mutation, with a positive rate of 21.1%. The overall response rate was 100%, only 16.7% achieved complete response. The overall regression rate of osseous lesions was 100%. Regression of central nervous system involvement was also favorable. After a median follow-up of 44 months, the estimated event-free survival was 48.9 months, the overall survival rate was 97.2%. The risk organ involvement showed strong prognostic value, EFS was 34.1 or 54.6 months (p = 0.001) in groups with/without risk organ involvement respectively. Neutropenia and thrombocytopenia were the most common adverse effects. CONCLUSION The regimen of methotrexate and cytosine arabinoside (MA) is effective and safe in treating adult LCH patients, and timely preventions may be considered for the high incidence of hematological adverse effects. TRIAL REGISTRATION Trial No. NCT02389400 on Clinicaltrials.gov, registered on 10th Mar. 2015.
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Pors J, Churg A. Cyclin D1 and BRAF V600E immunohistochemical staining in pulmonary Langerhans cell histiocytosis. Histopathology 2020; 76:1091-1093. [PMID: 31965621 DOI: 10.1111/his.14068] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 11/29/2022]
Affiliation(s)
- Jennifer Pors
- Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada
| | - Andrew Churg
- Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada
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40
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Jouenne F, Chevret S, Bugnet E, Clappier E, Lorillon G, Meignin V, Sadoux A, Cohen S, Haziot A, How-Kit A, Kannengiesser C, Lebbé C, Gossot D, Mourah S, Tazi A. Genetic landscape of adult Langerhans cell histiocytosis with lung involvement. Eur Respir J 2020; 55:13993003.01190-2019. [PMID: 31806714 DOI: 10.1183/13993003.01190-2019] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2019] [Accepted: 11/13/2019] [Indexed: 12/12/2022]
Abstract
The clinical significance of the BRAF V600E mutation in adult Langerhans cell histiocytosis (LCH), including pulmonary Langerhans cell histiocytosis (PLCH), is not well understood. Similarly, the spectrum of molecular alterations involved in adult LCH has not been fully delineated. To address these issues, we genotyped a large number of adult LCH biopsies and searched for an association of identified molecular alterations with clinical presentation and disease outcome.Biopsies from 117 adult LCH patients, 83 with PLCH (median age 36.4 years, 56 females, 38 multisystem disease, 79 single system disease, 65 current smokers) were genotyped for the BRAF V600E mutation. In 69 cases, LCH lesions were also genotyped by whole-exome sequencing (WES) or targeted gene panel next-generation sequencing (NGS). Cox models were used to estimate the association of baseline characteristics with the hazard of LCH progression.MAPK pathway alterations were detected in 59 out of 69 cases (86%) (BRAF V600E mutation: 36%, BRAF N486_P490 deletion: 28%, MAP2K1 mutations: 15%, isolated NRAS Q61 mutations: 4%), while KRAS mutations were virtually absent in PLCH lesions. The BRAF V600E mutation was not associated with LCH presentation at diagnosis, including smoking status and lung function, in PLCH patients. BRAF V600E status did not influence the risk of LCH progression over time.Thus, MAPK alterations are present in most lesions from adult LCH patients, particularly in PLCH. Unlike reports in paediatric LCH, BRAF V600E genotyping did not provide additional information on disease outcome. The search for alterations involved in the MAPK pathway, including BRAF deletions, is useful for guiding targeted treatment in selected patients with refractory progressive LCH.
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Affiliation(s)
- Fanélie Jouenne
- Université de Paris, INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire de Pharmacogénomique, Paris, France
| | - Sylvie Chevret
- Université de Paris, U1153 CRESS, Équipe de Recherche en Biostatistiques et Épidémiologie Clinique (ECSTRRA), Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service de Biostatistique et Information Médicale, Paris, France
| | - Emmanuelle Bugnet
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, Paris, France
| | - Emmanuelle Clappier
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'Hématologie Biologique, Paris, France.,Université de Paris, INSERM U944, Institut de Recherche Saint-Louis, Paris, France
| | - Gwenaël Lorillon
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, Paris, France
| | - Véronique Meignin
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service de Pathologie, INSERM UMR_S1165, Paris, France
| | - Aurélie Sadoux
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire de Pharmacogénomique, Paris, France
| | - Shannon Cohen
- INSERM U1160, Institut de Recherche Saint-Louis, Paris, France
| | - Alain Haziot
- INSERM U1160, Institut de Recherche Saint-Louis, Paris, France
| | - Alexandre How-Kit
- Laboratoire de Génomique Fonctionnelle, Fondation Jean Dausset - CEPH, Paris, France
| | - Caroline Kannengiesser
- Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Laboratoire de Génétique, Paris, France
| | - Céleste Lebbé
- Université de Paris, INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Département de Dermatologie, Paris, France
| | - Dominique Gossot
- Institut du Thorax Curie-Montsouris, Département Thoracique, Institut Mutualiste Montsouris, Paris, France
| | - Samia Mourah
- Université de Paris, INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire de Pharmacogénomique, Paris, France
| | - Abdellatif Tazi
- Université de Paris, INSERM U976, Institut de Recherche Saint-Louis, Paris, France .,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, Paris, France
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Liu H, Osterburg AR, Flury J, Swank Z, McGraw DW, Gupta N, Wikenheiser-Brokamp KA, Kumar A, Tazi A, Inoue Y, Hirose M, McCormack FX, Borchers MT. MAPK mutations and cigarette smoke promote the pathogenesis of pulmonary Langerhans cell histiocytosis. JCI Insight 2020; 5:132048. [PMID: 31961828 DOI: 10.1172/jci.insight.132048] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 01/15/2020] [Indexed: 12/12/2022] Open
Abstract
Pulmonary Langerhans cell histiocytosis (PLCH) is a rare smoking-related lung disease characterized by dendritic cell (DC) accumulation, bronchiolocentric nodule formation, and cystic lung remodeling. Approximately 50% of patients with PLCH harbor somatic BRAF-V600E mutations in cells of the myeloid/monocyte lineage. However, the rarity of the disease and lack of animal models have impeded the study of PLCH pathogenesis. Here, we establish a cigarette smoke-exposed (CS-exposed) BRAF-V600E-mutant mouse model that recapitulates many hallmark characteristics of PLCH. We show that CD11c-targeted expression of BRAF-V600E increases DC responsiveness to stimuli, including the chemokine CCL20, and that mutant cell accumulation in the lungs of CS-exposed mice is due to both increased cellular viability and enhanced recruitment. Moreover, we report that the chemokine CCL7 is secreted from DCs and human peripheral blood monocytes in a BRAF-V600E-dependent manner, suggesting a possible mechanism for recruitment of cells known to dominate PLCH lesions. Inflammatory lesions and airspace dilation in BRAF-V600E mice in response to CS are attenuated by transitioning animals to filtered air and treatment with a BRAF-V600E inhibitor, PLX4720. Collectively, this model provides mechanistic insights into the role of myelomonocytic cells and the BRAF-V600E mutation and CS exposure in PLCH pathogenesis and provides a platform to develop biomarkers and therapeutic targets.
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Affiliation(s)
- Huan Liu
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Andrew R Osterburg
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Jennifer Flury
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Zulma Swank
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Dennis W McGraw
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.,Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA
| | - Nishant Gupta
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.,Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA
| | - Kathryn A Wikenheiser-Brokamp
- Division of Pathology and Laboratory Medicine and.,Perinatal Institute, Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.,Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, USA
| | - Ashish Kumar
- Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
| | - Abdellatif Tazi
- INSERM UMR-S 976, University Paris-Diderot, Sorbonne Paris Cité, Paris, France
| | - Yoshikazu Inoue
- National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Masaki Hirose
- National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Francis X McCormack
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.,Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA
| | - Michael T Borchers
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.,Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA
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Le Guen P, Chevret S, Bugnet E, de Margerie-Mellon C, Lorillon G, Seguin-Givelet A, Jouenne F, Gossot D, Vassallo R, Tazi A. Management and outcomes of pneumothorax in adult patients with Langerhans cell Histiocytosis. Orphanet J Rare Dis 2019; 14:229. [PMID: 31639032 PMCID: PMC6805357 DOI: 10.1186/s13023-019-1203-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/13/2019] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Pneumothorax may recur during pulmonary Langerhans cell histiocytosis (PLCH) patients' follow-up and its management is not standardised. The factors associated with pneumothorax recurrence are unknown. METHODS In this retrospective study, PLCH patients who experienced a pneumothorax and were followed for at least 6 months after the first episode were eligible. The objectives were to describe the treatment of the initial episode and pneumothorax recurrences during follow-up. We also searched for factors associated with pneumothorax recurrence and evaluated the effect on lung function outcome. Time to recurrence was estimated by the Kaplan Meier method and the cumulative hazard of recurrence handling all recurrent events was estimated. Univariate Cox models and Andersen-Gill counting process were used for statistical analyses. RESULTS Fourty-three patients (median age 26.5 years [interquartile range (IQR), 22.9-35.4]; 26 men, 39 current smokers) were included and followed for median time of 49 months. Chest tube drainage was the main management of the initial pneumothorax, which resolved in 70% of cases. Pneumothorax recurred in 23 (53%) patients, and overall 96 pneumothoraces were observed during the study period. In the subgroup of patients who experienced pneumothorax recurrence, the median number of episodes per patient was 3 [IQR, 2-4]. All but one recurrence occurred within 2 years after the first episode. Thoracic surgery neither delayed the time of occurrence of the first ipsilateral recurrence nor reduced the overall number of recurrences during the study period, although the rate of recurrence was lower after thoracotomy than following video-assisted thoracic surgery (p = 0.03). At the time of the first pneumothorax, the presence of air trapping on lung function testing was associated with increased risk of recurrence (hazard ratio = 5.08; 95% confidence interval [1.18, 21.8]; p = 0.03). Pneumothorax recurrence did not predict subsequent lung function decline (p = 0.058). CONCLUSIONS Our results show that pneumothorax recurrences occur during an "active" phase of PLCH. In this observational study, the time of occurrence of the first ipsilateral recurrence and the overall number of pneumothorax recurrences were similar after conservative and thoracic surgical treatments. Further studies are needed to determine the best management to reduce the risk of pneumothorax recurrence in PLCH patients.
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Affiliation(s)
- Pierre Le Guen
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France
| | - Sylvie Chevret
- Université de Paris, U1153 CRESS, Equipe de Recherche en Biostatistiques et Epidémiologie Clinique (ECSTRRA), Paris, France.,Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service de Biostatistique et Information Médicale, Paris, France
| | - Emmanuelle Bugnet
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France
| | - Constance de Margerie-Mellon
- Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Service de Radiologie, Paris, France
| | - Gwenaël Lorillon
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France
| | - Agathe Seguin-Givelet
- Département Thoracique, Institut du Thorax Curie-Montsouris, Institut Mutualiste Montsouris, Paris, France
| | - Fanélie Jouenne
- Université de Paris, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire de Pharmacologie Biologique, Paris, France
| | - Dominique Gossot
- Département Thoracique, Institut du Thorax Curie-Montsouris, Institut Mutualiste Montsouris, Paris, France
| | - Robert Vassallo
- Departments of Medicine, Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA
| | - Abdellatif Tazi
- Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Centre National de Référence des Histiocytoses, Service de Pneumologie, 1 Avenue Claude Vellefaux, 75475, Paris, Cedex 10, France. .,Université de Paris, U1153 CRESS, Equipe de Recherche en Biostatistiques et Epidémiologie Clinique (ECSTRRA), Paris, France.
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Karamova AE, Chikin VV, Znamenskaya LF, Nefedova MA, Mikhina VA, Battalova NS. Langerhans cell histiocytosis in an adult patient. VESTNIK DERMATOLOGII I VENEROLOGII 2019. [DOI: 10.25208/0042-4609-2019-95-4-57-66] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
Aim: to present a clinical case of a rare dermatosis — Langerhans cell histiocytosis (LCH) in an adult patient.Materials and methods. A clinical and laboratory examination of a 64-year-old woman who had complained of rashes on the skin of the scalp, neck, trunk and lower extremities accompanied by itching was carried out. A histological study of skin biopsy samples from the lesion area, as well as an immunohistochemical study of Langerhans cell markers — langerin and S-100 protein — were performed.Results. Clinical manifestations of the disease, the presence of histiocytic infiltrate in the epidermis and dermis during the histological study and immunohistochemical detection of langerin infiltrate cells and S-100 protein were all consistent with the diagnosis of LCH. The therapy with methotrexate subcutaneously significantly improved the patient’s condition.Conclusion. Verification of the LCH diagnosis requires a histological study of skin biopsy samples and an immunohistochemical study of Langerhans cell markers. The efficacy of methotrexate in the treatment of this disease has been confirmed.
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Affiliation(s)
- A. E. Karamova
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
| | - V. V. Chikin
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
| | - L. F. Znamenskaya
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
| | - M. A. Nefedova
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
| | - V. A. Mikhina
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
| | - N. S. Battalova
- State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation
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Goyal G, Young JR, Koster MJ, Tobin WO, Vassallo R, Ryu JH, Davidge-Pitts CJ, Hurtado MD, Ravindran A, Sartori Valinotti JC, Bennani NN, Shah MV, Rech KL, Go RS. The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease. Mayo Clin Proc 2019; 94:2054-2071. [PMID: 31472931 DOI: 10.1016/j.mayocp.2019.02.023] [Citation(s) in RCA: 118] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 02/14/2019] [Accepted: 02/22/2019] [Indexed: 12/25/2022]
Abstract
Histiocytic neoplasms, a rare and heterogeneous group of disorders, primarily include Erdheim-Chester disease, Langerhans cell histiocytosis, and Rosai-Dorfman disease. Due to their diverse clinical manifestations, the greatest challenge posed by these neoplasms is the establishment of a diagnosis, which often leads to a delay in institution of appropriate therapy. Recent insights into their genomic architecture demonstrating mitogen-activated protein kinase/extracellular signal-regulated kinase pathway mutations have now enabled potential treatment with targeted therapies in most patients. This consensus statement represents a joint document from a multidisciplinary group of physicians at Mayo Clinic who specialize in the management of adult histiocytic neoplasms. It consists of evidence- and consensus-based recommendations on when to suspect these neoplasms and what tests to order for the diagnosis and initial evaluation. In addition, it also describes the histopathologic and individual organ manifestations of these neoplasms to help the clinicians in identifying their key features. With uniform guidelines that aid in identifying these neoplasms, we hope to improve the awareness that may lead to their timely and correct diagnosis.
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Affiliation(s)
- Gaurav Goyal
- Division of Hematology, Mayo Clinic, Rochester, MN.
| | | | | | | | - Robert Vassallo
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | - Jay H Ryu
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN
| | | | - Maria D Hurtado
- Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, Rochester, MN
| | | | | | | | | | - Karen L Rech
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
| | - Ronald S Go
- Division of Hematology, Mayo Clinic, Rochester, MN.
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Huang H, Lu T, Sun Y, Li S, Li J, Xu K, Feng RE, Xu ZJ. Association between clinicopathologic characteristics and BRAF V600E expression in Chinese patients with Langerhans cell histiocytosis. Thorac Cancer 2019; 10:1984-1992. [PMID: 31441596 PMCID: PMC6775012 DOI: 10.1111/1759-7714.13179] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 08/08/2019] [Accepted: 08/09/2019] [Indexed: 12/22/2022] Open
Abstract
Background The identification of V‐raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E mutations has been recommended in patients with Langerhans cell histiocytosis (LCH) with difficult diagnosis and failure of first‐line treatment. The reported frequencies of BRAFV600E mutations vary in Chinese patients with LCH. Methods We conducted a retrospective analysis of LCH patients with a definitive pathological diagnosis who were hospitalized between 2013 and 2017. The BRAFV600E mutations were detected with the human BRAFV600E amplification refractory mutation system‐PCR (ARMS‐PCR) kit from the collected tissue samples. Results This study consisted of 46 male (68.7%) and 21 female (31.3%) patients, with a mean age of 29.1 years (range, 2–76 years). Most were adults (45/67.2%) with the multisysytem‐LCH (MS‐LCH) disease subtype (49/61.3%). The overall frequency of BRAFV600E mutations was 22.4% (15 of 67 patients), confirmed by PCR analysis. These mutations were not closely correlated with age (nonadults vs. adults = 5/22.7% vs. 10/22.2%, P = 0.54), gender (female vs. male = 9/19.6% vs. 6/28.6%, P = 0.61), LCH classification type (single system: MS‐risk organ+: MS‐risk organ− = 3/16.7%: 12:28.6%: 0, P = 0.19) or prognosis (cured: improved/stable: exacerbated: died = 4/44.4%: 19.2%: 20%: 0, P = 0.37). There were 33 patients (49.2%) with lung involvement, and 12 patients (36.3%) underwent lung biopsies; after screening, four patients were diagnosed with solitary pulmonary LCH, all of whom were negative for BRAFV600E mutations. Conclusion The BRAFV600E mutation rate in patients with LCH was lower than those reported in other studies. In addition, BRAFV600E mutations might not be correlated with age, gender, LCH classification type or prognosis for Chinese cases.
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Affiliation(s)
- Hui Huang
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Tao Lu
- Pathological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yuxin Sun
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Shan Li
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ji Li
- Pathological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Kai Xu
- Radiological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Rui E Feng
- Pathological Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Zuo Jun Xu
- Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
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Liu X, Zhang Y, Zhou CX. High Prevalence of BRAF V600E Mutations in Langerhans Cell Histiocytosis of Head and Neck in Chinese Patients. Int J Surg Pathol 2019; 27:836-843. [PMID: 31203679 DOI: 10.1177/1066896919855774] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Langerhans cell histiocytosis (LCH) is characterized by clonal proliferation of Langerhans cells and has been classified as a hematolymphoid tumor. BRAF V600E mutation was found to be frequent in LCH; however, it has also been reported that Asia patients with LCH tend to show a lower rate of BRAF V600E mutation. In this study, we found LCH from the head and neck region often involved bone especially the posterior of the mandible and presented a high prevalence of BRAF V600E mutation in Chinese patients. Our findings also showed immunohistochemical detection correlated very well to DNA sequencing of BRAF alterations, which may be useful in the diagnosis of LCH, especially in cases with a low proportion of Langerhans cells, and BRAF inhibitors might be a treatment option for patients with LCH harboring BRAF V600E mutation.
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Affiliation(s)
- Xiaoxiao Liu
- Peking University School and Hospital of Stomatology, Beijing, People's Republic of China
| | - Ye Zhang
- Peking University School and Hospital of Stomatology, Beijing, People's Republic of China
| | - Chuan-Xiang Zhou
- Peking University School and Hospital of Stomatology, Beijing, People's Republic of China
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Abstract
Histiocytic and dendritic cell neoplasms are very rare, belonging to a group that share morphologic, immunophenotypic, and ultrastructural characteristics of mature histiocytic/dendritic neoplasms. Histiocytic and dendritic cell neoplasms may arise de novo or in association with B-cell, T-cell, or myeloid neoplasms. Recent molecular findings, particularly the discoveries of the mutations in the RAS-RAF-MEK-ERK pathway, have greatly advanced the diagnosis and treatment options. Histiocytic and dendritic cell neoplasms may closely resemble each other, non-hematopoietic neoplasms, and even reactive processes. Therefore, it is essential to understand the clinicopathologic characteristics, differential diagnoses, and pitfalls of each entity.
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Affiliation(s)
- Zenggang Pan
- Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510-3218, USA
| | - Mina L Xu
- Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510-3218, USA; Department of Laboratory Medicine, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06510-3218, USA.
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Kobayashi M, Tojo A. Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment. Cancer Sci 2018; 109:3707-3713. [PMID: 30281871 PMCID: PMC6272080 DOI: 10.1111/cas.13817] [Citation(s) in RCA: 107] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 09/24/2018] [Accepted: 09/29/2018] [Indexed: 12/27/2022] Open
Abstract
Langerhans cell histiocytosis (LCH) is a rare systemic disorder characterized by the accumulation of CD1a+/Langerin+ LCH cells and wide-ranging organ involvement. Langerhans cell histiocytosis was formerly referred to as histiocytosis X, until it was renamed in 1987. Langerhans cell histiocytosis β was named for its morphological similarity to skin Langerhans cells. Studies have shown that LCH cells originate from myeloid dendritic cells rather than skin Langerhans cells. There has been significant debate regarding whether LCH should be defined as an immune disorder or a neoplasm. A breakthrough in understanding the pathogenesis of LCH occurred in 2010 when a gain-of-function mutation in BRAF (V600E) was identified in more than half of LCH patient samples. Studies have since reported that 100% of LCH cases show ERK phosphorylation, indicating that LCH is likely to be a clonally expanding myeloid neoplasm. Langerhans cell histiocytosis is now defined as an inflammatory myeloid neoplasm in the revised 2016 Histiocyte Society classification. Randomized trials and novel approaches have led to improved outcomes for pediatric patients, but no well-defined treatments for adult patients have been developed to date. Although LCH is not fatal in all cases, delayed diagnosis or treatment can result in serious impairment of organ function and decreased quality of life. This study summarizes recent advances in the pathophysiology and treatment of adult LCH, to raise awareness of this "orphan disease".
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Affiliation(s)
- Masayuki Kobayashi
- Division of Molecular TherapyAdvanced Clinical Research CenterInstitute of Medical ScienceThe University of TokyoTokyoJapan
| | - Arinobu Tojo
- Division of Molecular TherapyAdvanced Clinical Research CenterInstitute of Medical ScienceThe University of TokyoTokyoJapan
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Abstract
Giant cell rich lesions of the temporal bone encompass a wide spectrum of disease that includes infectious, reactive, and neoplastic processes. When dealing with any lesion that can potentially involve bone, it is important to understand both the clinical presentation and to correlate the histologic findings with the radiologic imaging. This review discusses the clinical, the pathologic features including the differential diagnosis, and the treatment of some of the more commonly encountered giant cell rich entities in this region.
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