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Glynn SE, Shenker R, Razavian NB, Patel Z, Steber C, Lanier CM, Farris J, Farris M, Chan M, Hughes RT. Extrapulmonary Small Cell Carcinoma: A Single-Institution Review of Brain Metastases, Treatment Paradigms, and Patient Outcomes. Cureus 2025; 17:e76974. [PMID: 39912007 PMCID: PMC11798624 DOI: 10.7759/cureus.76974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2025] [Indexed: 02/07/2025] Open
Abstract
Purpose Small cell carcinoma of the lung (SCLC) often presents with brain metastases, with most patients developing them within a few years of diagnosis. Prophylactic cranial irradiation (PCI) is commonly recommended. Extrapulmonary small cell carcinoma (EPSCC) is rare, and its metastatic pattern is not well understood. This study reviews brain metastases in EPSCC patients at a single institution, focusing on management and overall survival (OS). Materials We identified EPSCC patients and analyzed their characteristics, treatment, and outcomes. Brain metastases were assessed through diagnostic imaging. Extracranial progression-free survival (ePFS) was defined as the time from diagnosis to progression outside the brain, while OS was defined as the time from diagnosis to death from any cause. Kaplan-Meier methods and log-rank tests were used for time-to-event analyses, and the cumulative incidence of brain metastasis was estimated with the competing risk of death. Statistical significance was set at p < 0.05. Results Of the 68 EPSCC patients with a median follow-up of 7.1 months, 66% were male with a median age of 68 years old. Common primary sites included genitourinary (32%) and gastrointestinal/hepatobiliary (22%). Brain metastases occurred in 12 patients (18%): five at diagnosis and seven during follow-up. The treatment of brain metastases varied, with four patients receiving whole-brain radiotherapy (WBRT), two receiving stereotactic radiosurgery (SRS), and one receiving both WBRT and SRS. The median OS was 10.0 months, with no significant survival difference between patients with (10.8 months) and without (9.4 months) brain metastases (p = 0.89). Conclusion EPSCC has a lower incidence of brain metastases than SCLC, and brain metastases do not significantly impact OS. Further research on brain imaging, PCI, and management strategies is warranted.
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Affiliation(s)
- Sarah E Glynn
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Rachel Shenker
- Radiation Oncology, Duke University Hospital, Durham, USA
| | - Niema B Razavian
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Zachary Patel
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Cole Steber
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Claire M Lanier
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Joshua Farris
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Michael Farris
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Michael Chan
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
| | - Ryan T Hughes
- Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, USA
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Kharrat G, Ferchichi S, Azaiez A, Ferjani M, Chalbi E, Marrakchi J. Agressive small cell neuroendocrine carcinoma of the neck: A case report. Int J Surg Case Rep 2024; 124:110341. [PMID: 39326373 PMCID: PMC11462040 DOI: 10.1016/j.ijscr.2024.110341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2024] [Revised: 09/18/2024] [Accepted: 09/21/2024] [Indexed: 09/28/2024] Open
Abstract
INTRODUCTION The location in the neck of small cell neuroendocrine carcinoma (SCNEC) is rare and aggressive with a poor prognosis. We herein describe an extremely uncommon example of cervical SCNEC probably arising in the parotid gland, diagnosed at an advanced metastatic stage. PRESENTATION OF CASE A 76 year old man, non-smoking, non-alcoholic presented a left cervical and rapidly progressive mass. It was suspicious of malignancy and located in the parotid space and II, III, IV and V lymph node groups. In two weeks, the patient had presented a rapid increase in size, with extensive skin permeation. CT scan revealed a large mass infiltrating the left parotid and submandibular glands compressing the jugulo-carotid vascular axis and liver metastases. Diagnosis was made on the morphological pathological examination supplemented by the immunohistochemistry examination, indeed, cells were immunoreactive for chromogranin A as well as synaptophysin. Chemotherapy based on cisplatin and Etoposide VP 16 was started but the evolution was unfavorable: death occurred after 2 cycles. CLINICAL DISCUSSION Neuroendocrine neoplasm arises from neural crest cells. Its location in the head and neck is extremely rare with a tendency for aggressive local invasion and a strong propensity for both regional and distant metastasis. Treatment may include surgical resection, radiotherapy, chemotherapy, or combination of these modalities. The prognosis is poor. CONCLUSION The clinician must discuss the diagnosis of cervical SCNEC when faced with a man in the seventh decade who presents an agressive rapidly expanding cervical mass. The diagnosis confirmation is pathological combining morphological and immunohistochemical evaluations.
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Affiliation(s)
- G Kharrat
- ENT department, Mohamed Taher Maâmouri University Hospital of Nabeul, Faculty of Medicine, El Manar University of Tunis, Tunisia.
| | - S Ferchichi
- ENT department, Mohamed Taher Maâmouri University Hospital of Nabeul, Faculty of Medicine, El Manar University of Tunis, Tunisia
| | - A Azaiez
- ENT department, Mohamed Taher Maâmouri University Hospital of Nabeul, Faculty of Medicine, El Manar University of Tunis, Tunisia
| | - M Ferjani
- ENT department, Mohamed Taher Maâmouri University Hospital of Nabeul, Faculty of Medicine, El Manar University of Tunis, Tunisia
| | - E Chalbi
- Pathology department, Mohamed Taher Maâmouri University Hospital of Nabeul, Faculty of Medicine, El Manar University of Tunis, Tunisia
| | - J Marrakchi
- Regional hospital of Menzel Bourguiba, Faculty of Medicine, El Manar University of Tunis, Tunisia
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Chen E, Yip PY, Tognela A, Gandy G, Earl C, Tran P, Kok PS. A comparison of the outcomes of pulmonary versus extrapulmonary extensive-stage small cell carcinoma. Intern Med J 2024; 54:414-420. [PMID: 38009656 DOI: 10.1111/imj.16281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Accepted: 11/02/2023] [Indexed: 11/29/2023]
Abstract
BACKGROUND Extrapulmonary small cell carcinomas (EPSCCs) are rare cancers, comprising 0.1-0.4% of all cancers. The scarcity of EPSCC studies has led current treatment strategies to be extrapolated from small cell lung cancer (SCLC), justified by analogous histological and clinical features. AIMS We conducted a retrospective cohort study comparing the outcomes of extensive-stage (ES) SCLC and EPSCC. METHODS Patients diagnosed with ES SCLC or EPSCC between 2010 and 2020 from four hospitals in Sydney were identified. Patients who received active treatment and best supportive care were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and overall response rates (ORRs). RESULTS Three hundred and eighty-four patients were included (43 EPSCC vs. 340 SCLC). EPSCC were of genitourinary (n = 15), unknown primary (n = 13) and gastrointestinal (n = 12) origin. Treatment modalities for EPSCC compared to SCLC included palliative chemotherapy (56% vs 73%), palliative radiotherapy (47% vs 59%) and consolidation chest radiotherapy (10% of SCLC). Overall, median OS was 6.4 versus 7 months for EPSCC versus SCLC respectively, but highest in prostate EPSCC (25.6 months). Of those who received chemotherapy (22 EPSCC vs 233 SCLC), median OS was 10.4 versus 8.4 months (HR OS 0.81, 95% confidence interval (CI): 0.5-1.31, P = 0.38); PFS was 5.4 versus 5.5 months (HR PFS 0.93, 95% CI: 0.58-1.46, P = 0.74) and ORR were 73% versus 68%. CONCLUSIONS EPSCC and SCLC appeared to have comparable OS and treatment outcomes. However, the wide range of OS in EPSCC highlights the need for an improved understanding of its genomics to explore alternative therapeutics.
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Affiliation(s)
- Emily Chen
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Po Y Yip
- Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia
| | - Annette Tognela
- Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia
| | - Geovanny Gandy
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
- Liverpool Hospital, Sydney, New South Wales, Australia
| | - Clare Earl
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Patrick Tran
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Peey-Sei Kok
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
- National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
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Tuan HX, Lieu DQ, Luan DT, Duc NM. Small-cell cancer of the perihilar bile duct with bleeding esophageal varices: A report of a rare case. J Clin Imaging Sci 2023; 13:30. [PMID: 37810178 PMCID: PMC10559499 DOI: 10.25259/jcis_53_2023] [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: 06/02/2023] [Accepted: 09/19/2023] [Indexed: 10/10/2023] Open
Abstract
Small-cell cancer is an uncommon histological subtype of neuroendocrine carcinoma. It frequently has a poor prognosis because of distant metastasis. It is diagnosed using histopathological and immunohistochemical tests. We report the case of a 29-year-old female with small-cell cancer in the perihilar bile duct who presented with bleeding esophageal varices. This case report aims to improve physicians' understanding of small-cell cancer, thereby helping to reduce the frequency of missed clinical diagnoses.
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Affiliation(s)
- Ho Xuan Tuan
- Department of Medical Imaging, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam
| | - Dau Quang Lieu
- Department of Internal Medicine, Hanoi Medical University Hospital, Ha Noi, Vietnam
| | - Dao-Thi Luan
- Department of Pathology, Hanoi Medical University, Ha Noi, Vietnam
| | - Nguyen Minh Duc
- Department of Radiology, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
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Sun Y, Zhang Y, Li R, Cai D, Zhang W, Yang Z. Intracranial dissemination in a primary small cell carcinoma of the brain: a case report and literature review. Front Oncol 2023; 13:1222961. [PMID: 37771442 PMCID: PMC10525323 DOI: 10.3389/fonc.2023.1222961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Accepted: 08/29/2023] [Indexed: 09/30/2023] Open
Abstract
Primary intracranial small cell carcinoma (SCC) is extremely rare with only 8 previously reported cases. We describe a case of primary intracranial SCC with intracranial metastasis. A 46-year-old man presented with decreased vision and a red and swollen left eye. Brain magnetic resonance imaging (MRI) revealed a heterogeneously enhanced tumor on the left frontal lobe. Preoperative systemic computed tomography (CT), MRI, and positron emission tomography (PET)-CT revealed no extracranial tumors. The tumor on the left frontal lobe was excised. Immunohistochemical staining on the excision showed positivity for CD56, synaptophysin (Syn), cytokeratin (CK), and Ki-67 (30%), and negativity for thyroid transcriptional factor-1 (TTF-1), glial fibrillary acidic protein (GFAP), B-cell lymphoma 6 (Bcl-6), multiple myeloma oncogene 1 (MUM-1), C-Myc, Vimentin, P40, P53, CK7, CD3, CD5, CD20, CD79a, CD10, and CD23. The pathological examination strongly suggested that the tumor was a primary intracranial SCC. One year after the surgery, the patient was readmitted with slurred speech and slow movements. Three well-defined tumors were found in the left upper frontal lobe by brain MRI. Tumor resection was then performed. Further immunohistochemical examination of the excised tissue displayed the same pattern as previously, indicating the recurrence of intracranial SCC in the left frontal lobe. The patient received adjuvant chemotherapy and radiotherapy after the tumor resection. At the 2-year follow-up, he remained asymptomatic.
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Affiliation(s)
- Yesheng Sun
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
| | - Ying Zhang
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
| | - Ruichun Li
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
| | - Dongpeng Cai
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
| | - Wei Zhang
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
| | - Zhiqian Yang
- Department of Neurosurgery, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
- Guangdong Provincial Engineering and Technology Research Center of Stem Cell Therapy for Pituitary Disease, Guangzhou, China
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Gandy G, Yip PY, Tognela A, Hayat F, Fox W, Kok PS. Outcomes of extensive stage extrapulmonary small cell cancer. Intern Med J 2023; 53:1556-1563. [PMID: 36043900 DOI: 10.1111/imj.15907] [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: 03/17/2022] [Accepted: 08/05/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Extrapulmonary small cell cancer (EPSCC) is a rare malignancy with an incidence of approximately 0.1%-0.4% of all cancers. Treatment of this disease is often based on small cell lung cancer. AIMS We aimed to investigate real-world clinical outcomes of patients with extensive-stage (ES) ESPCC. METHODS Patients diagnosed with ES EPSCC between 2010 and 2020 from multiple centres in New South Wales were identified. Patient, disease and treatment characteristics were collected and presented using descriptive statistics. Survival was analysed using the Kaplan-Meier method. Univariate and multivariate Cox regression hazard models were used to identify potential prognostic factors. RESULTS Sixty eligible ES EPSCC patients were identified, including 65% male and 35% female. The mean age was 69 years (range 37-88). Forty-five per cent were never smokers, 42% ex-smokers and 13% current smokers, and 17% of patients had limited-stage disease prior to development of ES disease. The most common primary sites were genitourinary (42%; mainly prostate (n = 14) and bladder (n = 10)), gastrointestinal (28%; mainly oesophagus (n = 5) and colon (n = 4)) and unknown primary (22%). Treatments received included palliative chemotherapy (67%), palliative radiotherapy (53%), palliative surgery (13%) and best supportive care alone (13%). The median overall survival (OS) was 8.0 months. The median progression-free survival was 5.4 months, and response rate to first-line chemotherapy was 65%. Platinum-based chemotherapy was prognostic of longer OS (HR 0.27, CI 0.12-0.60, P = 0.001). CONCLUSIONS Patients with ES EPSCC had good response to palliative chemotherapy, but OS remained poor. Further research is required to improve the prognosis in this population.
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Affiliation(s)
- Geovanny Gandy
- Liverpool Hospital, Sydney, New South Wales, Australia
- Western Sydney University, Sydney, New South Wales, Australia
| | - Po Yee Yip
- Western Sydney University, Sydney, New South Wales, Australia
- Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia
| | - Annette Tognela
- Western Sydney University, Sydney, New South Wales, Australia
- Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, New South Wales, Australia
| | - Faisal Hayat
- Mid North Coast Cancer Institute, Coffs Harbour Hospital, Coffs Harbour, New South Wales, Australia
| | - William Fox
- Mid North Coast Cancer Institute, Coffs Harbour Hospital, Coffs Harbour, New South Wales, Australia
| | - Peey Sei Kok
- Western Sydney University, Sydney, New South Wales, Australia
- National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
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Zhang X. An online tool for survival prediction of extrapulmonary small cell carcinoma with random forest. Front Oncol 2023; 13:1166424. [PMID: 37456228 PMCID: PMC10346459 DOI: 10.3389/fonc.2023.1166424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/12/2023] [Indexed: 07/18/2023] Open
Abstract
Purpose Extrapulmonary small cell carcinoma (EPSCC) is rare, and its knowledge is mainly extrapolated from small cell lung carcinoma. Reliable survival prediction tools are lacking. Methods A total of 3,921 cases of EPSCC were collected from the Surveillance Epidemiology and End Results (SEER) database, which form the training and internal validation cohorts of the survival prediction model. The endpoint was an overall survival of 0.5-5 years. Internal validation performances of machine learning algorithms were compared, and the best model was selected. External validation (n = 68) was performed to evaluate the generalization ability of the selected model. Results Among machine learning algorithms, the random forest model performs best on internal validation, whose area under the curve (AUC) is 0.736-0.800. The net benefit is higher than the TNM classification in decision curve analysis. The AUC of this model on the external validation cohort is 0.739-0.811. This model was then deployed online as a free, publicly available prediction tool of EPSCC (http://42.192.80.13:4399/). Conclusion This study provides an excellent online survival prediction tool for EPSCC with machine learning and large-scale data. Age, TNM stages, and surgery (including potential performance status information) are the most critical factors for the prediction model.
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Affiliation(s)
- Xin Zhang
- Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China
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A rare localization of small-cell carcinoma in head and neck area: case report. THE EGYPTIAN JOURNAL OF OTOLARYNGOLOGY 2022. [DOI: 10.1186/s43163-022-00337-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Abstract
Background
Small-cell carcinoma (SMCC) of hypopharynx is an extreme rare entity in the head and neck region. It is commonly arising from pulmonary in origin. We report a rare case of small-cell carcinoma of hypopharynx that caused upper airway obstruction in an elderly gentleman.
Case presentation
A 67-year-old man is presented to otorhinolaryngology clinic with a 4-month history of worsening shortness of breath and stridor. He was heavy tobacco smoker for 60 pack-years. Flexible nasopharyngolaryngoscopy revealed a large mass at the right pyriform fossa extending superiorly and obstructing the laryngeal inlet. He underwent tracheostomy, examination under general anesthesia with tissue biopsy. Histology from tissue biopsy revealed small-cell carcinoma. The positron emission tomography-CT showed exophytic mass from right pyriform sinus with regional and lung pleural metastasis as well. There was the absence of formal staging system for SMCC due to its limited and rare incidence. He was treated with combination of carboplatin and etoposide, similar to the regime for cell carcinoma of lung. The tumor regressed loco-regionally, and his pleural metastasis had shrunk to sub-centimeter in size.
Conclusions
To date, there is very limited data available on head and neck small cell carcinomas to guide treatment recommendations as well as staging system. Paucity of clinical data and outcome about this rare malignancy makes this report a valuable piece of experience to be shared together with existing literature.
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Morizane C, Machida N, Honma Y, Okusaka T, Boku N, Kato K, Nomura S, Hiraoka N, Sekine S, Taniguchi H, Okano N, Yamaguchi K, Sato T, Ikeda M, Mizuno N, Ozaka M, Kataoka T, Ueno M, Kitagawa Y, Terashima M, Furuse J. Effectiveness of Etoposide and Cisplatin vs Irinotecan and Cisplatin Therapy for Patients With Advanced Neuroendocrine Carcinoma of the Digestive System: The TOPIC-NEC Phase 3 Randomized Clinical Trial. JAMA Oncol 2022; 8:1447-1455. [PMID: 35980649 PMCID: PMC9389440 DOI: 10.1001/jamaoncol.2022.3395] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Question For patients with advanced neuroendocrine carcinoma of the digestive system, which of the 2 community standard regimens is more effective: etoposide plus cisplatin (EP) or irinotecan plus cisplatin (IP)? Findings In this randomized clinical trial of 170 patients who were chemotherapy naive and had recurrent or unresectable neuroendocrine carcinoma of the digestive system, median overall survival was 12.5 months in the EP arm and 10.9 months in the IP arm. Meaning Both EP and IP therapy remain standard first-line chemotherapy options. Importance Etoposide plus cisplatin (EP) and irinotecan plus cisplatin (IP) are commonly used as community standard regimens for advanced neuroendocrine carcinoma (NEC). Objective To identify whether EP or IP is a more effective regimen in terms of overall survival (OS) in patients with advanced NEC of the digestive system. Design, Setting, and Participants This open-label phase 3 randomized clinical trial enrolled chemotherapy-naive patients aged 20 to 75 years who had recurrent or unresectable NEC (according to the 2010 World Health Organization classification system) arising from the gastrointestinal tract, hepatobiliary system, or pancreas. Participants were enrolled across 50 institutions in Japan between August 8, 2014, and March 6, 2020. Interventions In the EP arm, etoposide (100 mg/m2/d on days 1, 2, and 3) and cisplatin (80 mg/m2/d on day 1) were administered every 3 weeks. In the IP arm, irinotecan (60 mg/m2/d on days 1, 8, and 15) and cisplatin (60 mg/m2/d on day 1) were administered every 4 weeks. Main Outcomes and Measures The primary end point was OS. In total, data from 170 patients were analyzed to detect a hazard ratio (HR) of 0.67 (median OS of 8 and 12 months in inferior and superior arms, respectively) with a 2-sided α of 10% and power of 80%. The pathologic findings were centrally reviewed following treatment initiation. Results Among the 170 patients included (median [range] age, 64 [29-75] years; 117 [68.8%] male), median OS was 12.5 months in the EP arm and 10.9 months in the IP arm (HR, 1.04; 90% CI, 0.79-1.37; P = .80). The median progression-free survival was 5.6 (95% CI, 4.1-6.9) months in the EP arm and 5.1 (95% CI, 3.3-5.7) months in the IP arm (HR, 1.06; 95% CI, 0.78-1.45). A subgroup analysis of OS demonstrated that EP produced more favorable OS in patients with poorly differentiated NEC of pancreatic origin (HR, 4.10; 95% CI, 1.26-13.31). The common grade 3 and 4 adverse events in the EP vs IP arms were neutropenia (75 of 82 [91.5%] patients vs 44 of 82 [53.7%] patients), leukocytopenia (50 of 82 [61.0%] patients vs 25 of 82 [30.5%] patients), and febrile neutropenia (FN) (22 of 82 [26.8%] patients vs 10 of 82 [12.2%] patients). While incidence of FN was initially high in the EP arm, primary prophylactic use of granulocyte colony-stimulating factor effectively reduced the incidence of FN. Conclusions and Relevance Results of this randomized clinical trial demonstrate that both EP and IP remain the standard first-line chemotherapy options. Although AEs were generally manageable, grade 3 and 4 AEs were more common in the EP arm. Trial Registration Japan Registry of Clinical Trials: jRCTs031180005; UMIN Clinical Trials Registry: UMIN000014795
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Affiliation(s)
| | | | | | | | | | - Ken Kato
- National Cancer Center Hospital, Tokyo, Japan
| | - Shogo Nomura
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan.,The University of Tokyo, Tokyo, Japan
| | | | | | | | - Naohiro Okano
- Kyorin University Faculty of Medicine, Mitaka, Japan
| | - Kensei Yamaguchi
- Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | | | | | - Masato Ozaka
- Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomoko Kataoka
- Japan Clinical Oncology Group Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan
| | | | | | | | - Junji Furuse
- Kyorin University Faculty of Medicine, Mitaka, Japan
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Caruso G, Sassu CM, Tomao F, Di Donato V, Perniola G, Fischetti M, Benedetti Panici P, Palaia I. The puzzle of gynecologic neuroendocrine carcinomas: State of the art and future directions. Crit Rev Oncol Hematol 2021; 162:103344. [PMID: 33933568 DOI: 10.1016/j.critrevonc.2021.103344] [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: 09/01/2020] [Revised: 04/05/2021] [Accepted: 04/25/2021] [Indexed: 10/21/2022] Open
Abstract
Primary gynecologic neuroendocrine carcinomas (gNECs) are a heterogeneous spectrum of rare and highly aggressive neoplasms, accounting for about 2% of all gynecologic malignancies, which mostly resemble the small cell lung carcinoma (SCLC). Due to the lack of standardized treatment guidelines, their management poses a noteworthy clinical challenge. Currently, cumulative data retrieved from the management of SCLC and from retrospective studies supports a multimodality strategy, based on surgery, chemotherapy, and radiotherapy. Nevertheless, the prognosis remains poor and recurrences are extremely frequent. Hence, there is an urgent need for novel treatment options and promising molecular targets. Recently, there has been an increasing interest on the potential role of immune checkpoint inhibitors, especially in the recurrent setting. However, only scant evidence exists and there is still a long road ahead. A solid collaboration between gynecologists and oncologists worldwide is required to improve the treatment of these puzzling tumors.
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Affiliation(s)
- Giuseppe Caruso
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy.
| | - Carolina Maria Sassu
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
| | - Federica Tomao
- Department of Gynecologic Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy
| | - Violante Di Donato
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
| | - Giorgia Perniola
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
| | - Margherita Fischetti
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
| | - Pierluigi Benedetti Panici
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
| | - Innocenza Palaia
- Department of Maternal and Child Health and Urological Sciences, University of Rome "Sapienza", Policlinico "Umberto I", Rome, Italy
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Primary small cell carcinoma of the adrenal gland: Case presentation of a rare extrapulmonary small cell carcinoma. Urol Case Rep 2020; 33:101320. [PMID: 33102022 PMCID: PMC7573820 DOI: 10.1016/j.eucr.2020.101320] [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: 06/05/2020] [Accepted: 06/22/2020] [Indexed: 12/03/2022] Open
Abstract
Small cell carcinoma (SCC) is an aggressive histologic subtype of neuroendocrine tumor and is most commonly of bronchogenic origin. However, it can present in an extrapulmonary fashion. Primary extrapulmonary small cell carcinoma (EPSCC) is a rare disease entity, especially within the genitourinary system and furthermore of the adrenal gland. There are scarce case reports that describe management of primary adrenal SCC. We present a case of localized primary adrenal SCC diagnosed on adrenal mass biopsy and successfully treated via neoadjuvant chemotherapy and extirpative surgery.
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Alfayez M. Primary small cell oesophageal carcinoma: A retrospective study of different treatment modalities. World J Clin Oncol 2020; 11:836-843. [PMID: 33200076 PMCID: PMC7643191 DOI: 10.5306/wjco.v11.i10.836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/29/2020] [Accepted: 09/11/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary small cell of esophageal carcinoma is an aggressive tumor with no established treatment guidelines. A treatment strategy was adopted based on small cell carcinoma of the lung because of many similar clinicopathological features. Here, we report one of the largest case series in a western population.
AIM To review the practice of treating small cell oesophageal cancer (SCOC) with different treatment modalities treated at our institution between 2001 and 2014.
METHODS A total of 28 cases of SCOC have been identified. All cases were identified with a ten-digit code known as the CHI number. Data was collected using a combination of an electronic database, case notes and the chemotherapy electronic prescribing system (chemocare). We collected information on age, gender, performance status, staging of the disease (limited stage vs extensive stage).
RESULTS The results showed 17 patients (61%) were diagnosed with limited stage small cell oesophageal cancer (LS-SCOC), while 11 patients (39%) were diagnosed with extensive stage small cell oesophageal cancer (ES-SCOC). The median age at diagnosis of SCOC was 72 years (range 52-86). The median survival for patients with ES-SCOC was 7 mo (95%CI: 1-12) vs LS-SCOC [median 23 mo (95%CI: 14-40)], P < 0.0001. Subgroup analysis of those who received treatment showed the median survival for patients who received palliative chemotherapy was 7 mo (95%CI: 1.5-12), concurrent chemoradiation 45 mo (95%CI: 38-) and sequential chemoradiation 20 mo (95%CI: 17-25), P < 0.0001.
CONCLUSION Our data strongly support the use of concurrent chemoradiation in the treatment of LS-SCOC in patients who are fit with no significant comorbidity.
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Affiliation(s)
- Mohammad Alfayez
- Faculty of Medicine, Umm Al-Qura University, Makkah 21514, Saudi Arabia
- King Abdullah Medical City, Makkah 21514, Saudi Arabia
- Beatson West of Scotland Cancer Centre, Glasgow G12 0YN, United Kingdom
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13
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Wang J, Liu D, Meng Y, Guo Y, Zhao M. Extrapulmonary small cell carcinoma of the external auditory canal: a case report and review of the literature. J Int Med Res 2020; 48:300060520946517. [PMID: 32851892 PMCID: PMC7457657 DOI: 10.1177/0300060520946517] [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] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Accepted: 07/09/2020] [Indexed: 12/02/2022] Open
Abstract
Extrapulmonary small cell carcinoma (EPSCC) affecting the external auditory canal (EAC) is uncommon. We herein report a case involving a 56-year-old man with EPSCC of the EAC who had a 48-year history of recurrent purulent discharge in both ears and a 20-day history of right ear pain and hemorrhage followed by incomplete right eyelid closure and an askew mouth. He underwent surgical removal of middle ear granulation tissue, residual ossicles, and a right EAC mass. Postoperatively, pathomorphological examination combined with immunohistochemical staining supported a diagnosis of small cell carcinoma. Radiation therapy at a dose of 60.06 Gy in 33 daily fractions was completed 1 month after surgery, and synchronous etoposide-cisplatin regimen chemotherapy was performed for two cycles and four sequential cycles. One year postoperatively, magnetic resonance imaging showed no tumor in the ear; however, computed tomography showed multiple liver space-occupying lesions that were considered to indicate liver metastasis. Further chemotherapy was performed, but the patient died 15 months postoperatively. This case indicates that timely and accurate chemoradiotherapy is likely the most reasonable approach to EPSCC of the EAC given the aggressiveness of this tumor.
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Affiliation(s)
- Jianyan Wang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second
Hospital of Jilin University, Changchun, Jilin Province, China
- Department of Otorhinolaryngology Head and Neck Surgery, The Third
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Danqing Liu
- Department of Otorhinolaryngology Head and Neck Surgery, The First
Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Yingdi Meng
- Department of Otorhinolaryngology Head and Neck Surgery, The Second
Hospital of Jilin University, Changchun, Jilin Province, China
| | - Yingyuan Guo
- Department of Otorhinolaryngology Head and Neck Surgery, The Second
Hospital of Jilin University, Changchun, Jilin Province, China
| | - Ming Zhao
- Department of Otorhinolaryngology Head and Neck Surgery, The Second
Hospital of Jilin University, Changchun, Jilin Province, China
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Kitagawa Y, Osumi H, Shinozaki E, Ota Y, Nakayama I, Suzuki T, Wakatsuki T, Ichimura T, Ogura M, Ooki A, Takahari D, Suenaga M, Chin K, Yamaguchi K. Safety and efficacy of amrubicin monotherapy in patients with platinum-refractory metastatic neuroendocrine carcinoma of the gastrointestinal tract: a single cancer center retrospective study. Cancer Manag Res 2019; 11:5757-5764. [PMID: 31417315 PMCID: PMC6599893 DOI: 10.2147/cmar.s201048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Accepted: 05/29/2019] [Indexed: 01/25/2023] Open
Abstract
Purpose Patients with gastrointestinal neuroendocrine carcinoma (GI-NEC) have poor prognoses. Although platinum-based combination chemotherapy is commonly used as first-line treatment, the benefit of amrubicin (AMR) and salvage chemotherapy in those who develop platinum-refractory GI-NEC remains unknown. This study aimed to evaluate the efficacy and safety of AMR monotherapy in patients with platinum-refractory GI-NEC. Patients and methods Platinum-refractory GI-NEC patients who received AMR monotherapy between April 2012 and September 2017 were retrospectively analyzed. The overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. PFS and OS were estimated using Kaplan-Meier methods and compared using log-rank tests. Results In total, 16 patients were enrolled. Of them, 13 (81.3%), 1 (6.2%), and 2 (12.5%) received cisplatin plus irinotecan, cisplatin plus etoposide, and fluoropyrimidine plus platinum, respectively, before AMR monotherapy. The primary sites of NEC included the esophagus (N=3, 18.8%), stomach (N=10, 62.5%), duodenum (N=1, 6.2%) and colorectum (N=2, 12.5%). Patients were administered a median of 3 (range, 1–15) cycles of AMR. The ORR was 6.3%, and the median PFS and OS were 2.9 months (95% CI: 1.7–7.4) and 13.8 months (95% CI: 7.9–23.5), respectively. Neutropenia was the most serious adverse event. Grade 3 or higher neutropenia and febrile neutropenia occurred in 50.0% and 6.2% of patients, respectively. Other nonhematological toxicities were not severe, and no treatment-related deaths occurred. The 10 patients who received subsequent chemotherapy after AMR had significantly longer OS than those who did not (17.3 months vs 8.9 months; p=0.018). The median PFS of those who received organ-specific subsequent chemotherapy after AMR was 3.8 months, which was longer than that of those who received prior AMR. Conclusion AMR is feasible with minimal side effects for platinum-refractory GI-NEC. Organ-specific subsequent chemotherapy after AMR may improve patient survival.
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Affiliation(s)
- Yusuke Kitagawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hiroki Osumi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Eiji Shinozaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yumiko Ota
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Izuma Nakayama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Suzuki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeru Wakatsuki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Ichimura
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mariko Ogura
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akira Ooki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Daisuke Takahari
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Mitsukuni Suenaga
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Keisho Chin
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kensei Yamaguchi
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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15
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Obi-Njoku O, Bell C, Menon PR, Shergill I. Incidental finding of a small cell neuroendocrine carcinoma of the ureter. BMJ Case Rep 2019; 12:12/7/e229290. [PMID: 31371331 DOI: 10.1136/bcr-2019-229290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
The ureter is an extremely rare site for small cell neuroendocrine carcinoma. We present a case of this disease in a patient who presented without urological symptoms. The multidisciplinary team proposed nephroureterectomy (if fit) or watchful waiting as management. After discussion with the patient a decision in favour of watchful waiting was made. We report her case including a review of the literature, and emphasise that although small cell neuroendocrine carcinomas can be very aggressive, they can remain asymptomatic.
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Affiliation(s)
- Obinna Obi-Njoku
- Urology, Wrexham Maelor Hospital, Wrexham, UK.,Urology, Whittington Hospital, London, UK
| | - Chris Bell
- Urology, Wrexham Maelor Hospital, Wrexham, UK
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Ishida H, Kasajima A, Onodera Y, Konno T, Maruyama S, Okamoto H, Sato C, Heishi T, Sakurai T, Taniyama Y, Takahashi M, Fujishima F, Jingu K, Ishioka C, Sasano H, Kamei T. A comparative analysis of clinicopathological factors between esophageal small cell and basaloid squamous cell carcinoma. Medicine (Baltimore) 2019; 98:e14363. [PMID: 30813135 PMCID: PMC6408094 DOI: 10.1097/md.0000000000014363] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 12/29/2018] [Accepted: 01/05/2019] [Indexed: 02/07/2023] Open
Abstract
Esophageal small cell carcinoma (E-SmCC) and basaloid squamous cell carcinomas (BSCCs) are both highly aggressive malignancies, but their detailed differences in clinical behaviors have remained virtually unknown. In addition, treatment strategies of the patients with E-SmCC have not been established. 29 cases of E-SmCC and 39 with BSCC were examined in this study to clarify the clinical features and outcome of the patients with E-SmCC and to compare the findings with those of BSCC. E-SmCCs presented a more advanced status than BSCC (TNM Stage: P = .002). Esophagectomy was performed in 15 small cell carcinoma patients and 14 were treated with non-surgical/systemic therapy. The clinical outcome of the small cell carcinoma cases was significantly worse than those with BSCC (P = .001), but results of a stage-stratified analysis revealed that the Stage I small cell carcinoma patients presented favorable prognosis (3-year survival rate 100%, n = 4). In contrast, among those with Stage II-IV, clinical outcome tended to be better in the systemic therapy group (3-year survival rate 49%, n = 13) than the surgically treated group (3-year survival rate 0%, n = 12). E-SmCC was a more aggressive neoplasm than BSCC. However, early detection could possibly improve the clinical outcome of patients with E-SmCC. Systemic therapy could also benefit the patients with advanced disease (Stage II-IV).
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Affiliation(s)
- Hirotaka Ishida
- Department of Gastroenterological Surgery
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Atsuko Kasajima
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
- Department of Pathology, Technical University Munich, Munich
- German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Yu Onodera
- Department of Gastroenterological Surgery
| | | | | | | | | | | | | | | | - Masanobu Takahashi
- Department of Medical Oncology, Tohoku University Hospital
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University
| | - Fumiyoshi Fujishima
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Keiichi Jingu
- Department of Radiation Oncology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Chikashi Ishioka
- Department of Medical Oncology, Tohoku University Hospital
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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17
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Tatullo M, Codispoti B, Makeeva I, Benincasa C, Spagnuolo G. From Mouth to Brain: Neuroendocrine Markers Play as a Crosstalk Among Oral and Neurodegenerative Diseases. Front Endocrinol (Lausanne) 2019; 10:378. [PMID: 31263455 PMCID: PMC6584809 DOI: 10.3389/fendo.2019.00378] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/28/2019] [Indexed: 11/24/2022] Open
Abstract
The neuroendocrine system consists of various cells distributed in non-endocrine functional structures, able to synthesize amines and peptides with both local (paracrine) and systemic (endocrine) effects. The presence of such cells, belonging to the neuroendocrine system, is highlighted by the presence of neuroendocrine markers: the most suggestive are chromogranin A, synaptophysin, S-100B protein and glial fibrillary acidic protein. The presence of neuroendocrine markers is commonly associated to the occurrence of neuroendocrine cancers, currently representing the 0.5 percent of all malignant tumors. Nevertheless, neuroendocrine markers have been found to be overexpressed in rare oral neuroendocrine tumors, but also in quite common inflammatory conditions, such as severe periodontitis. The monitoring of neuroendocrine markers is, thus, a common factor of interest among dentistry and neurology: the analysis of neuroendocrine markers in oral diseases may be predictive and prognostic about the severity of neurological diseases, such as lateral amyotrophic sclerosis and traumatic brain injuries. The aim of this mini-review is to highlight the role of neuroendocrine molecules as advantageous diagnostic and prognostic markers for both oral diseases and neurodegenerative disorders.
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Affiliation(s)
- Marco Tatullo
- Biomedical Section, Tecnologica Research Institute, Crotone, Italy
- Department of Therapeutic Dentistry, Sechenov University Russia, Moscow, Russia
- *Correspondence: Marco Tatullo
| | - Bruna Codispoti
- Biomedical Section, Tecnologica Research Institute, Crotone, Italy
| | - Irina Makeeva
- Department of Therapeutic Dentistry, Sechenov University Russia, Moscow, Russia
| | | | - Gianrico Spagnuolo
- Department of Therapeutic Dentistry, Sechenov University Russia, Moscow, Russia
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, Università di Napoli Federico II, Naples, Italy
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18
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Sanguedolce F, Russo D, Mancini V, Selvaggio O, Calò B, Carrieri G, Cormio L. Morphological and Immunohistochemical Biomarkers in Distinguishing Prostate Carcinoma and Urothelial Carcinoma: A Comprehensive Review. Int J Surg Pathol 2018; 27:120-133. [DOI: 10.1177/1066896918814198] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The differential diagnosis between high-grade prostate carcinoma and infiltrating urothelial carcinoma (UC) in transurethral resection prostate specimens as well as cystoprostatectomy specimens may often be challenging due to morphologic and clinical overlap of the 2 entities. Such distinction has critical therapeutic and staging consequences, yet it is hampered by both issues in morphology and by the low accuracy rates of single immunohistochemical markers, as reported in literature. This review aims to provide a comprehensive analysis of the available morphological and immunohistochemical parameters, which may allow to discriminate between prostate carcinoma and urothelial carcinoma in the proper clinical context and to discuss their diagnostic applications in daily practice.
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19
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Patibandla JR, Fehniger JE, Levine DA, Jelinic P. Small cell cancers of the female genital tract: Molecular and clinical aspects. Gynecol Oncol 2018; 149:420-427. [PMID: 29458976 DOI: 10.1016/j.ygyno.2018.02.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 02/06/2018] [Accepted: 02/10/2018] [Indexed: 11/19/2022]
Abstract
OBJECTIVE Extra-pulmonary small cell carcinomas of the gynecologic tract (EPSCC-GTs) are a rare group of aggressive malignancies associated with poor prognoses and limited treatment options. Here, we review the clinical and molecular aspects of EPSCC-GTs and discuss how understanding their molecular features can assist in their diagnosis and the identification of novel effective treatments. METHODS We searched PubMed and Scopus for articles using the following keywords: "small cell carcinoma" in combination with "neuroendocrine", "ovary", "vagina", "fallopian tube", "vulva", "endometrium", "uterus", "cervix", or "gynecologic". Articles were limited to those published in English from January 1984 to October 2017. RESULTS EPSCC-GTs account for 2% of all gynecologic malignancies. The molecular features of EPSCC-GTs are largely understudied and unknown, with the exception of small cell carcinoma (SCC) of the ovary, hypercalcemic type (SCCOHT) and SCC of the cervix (SCCC). In nearly all cases, SCCOHT displays mutation in a single gene, SMARCA4, a member of the SWI/SNF chromatin remodeling complex. The loss of expression of the SWI/SNF protein SMARCA2 is another feature of SCCOHT. Dual negative staining for SMARCA2 and SMARCA4 is specific for SCCOHT and is generally used by gynecologic pathologists for the accurate diagnosis of this malignancy. Mutational analysis of SCCC has shown alterations in PIK3CA, KRAS and TP53, of which the last is the most common, although other actionable mutations have been identified. The molecular features of other EPSCC-GTs are largely unknown. CONCLUSIONS Due to their rarity, the majority of EPSCC-GTs are understudied and poorly understood. As demonstrated in the case of SCCOHT, unraveling the mutational profiles of these tumors can lead to improved diagnosis and the identification of novel therapeutic targets.
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Affiliation(s)
- Jay R Patibandla
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States
| | - Julia E Fehniger
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States
| | - Douglas A Levine
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States
| | - Petar Jelinic
- Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, United States.
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20
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Kanat O, Kilickap S, Korkmaz T, Oven BBU, Canhoroz M, Cubukcu E, Tolunay S, Evrensel T, Manavoglu O. Primary small cell carcinoma of the breast: Report of seven cases and review of the literature. TUMORI JOURNAL 2018; 97:473-8. [DOI: 10.1177/030089161109700410] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Aims and background The aim of the study was to analyze the clinicopathological characteristics, treatment modalities, and clinical outcome of patients with primary small cell carcinoma of the breast. Methods Fifty-three cases of primary small cell carcinoma of the breast were identified; 7 cases in this series and 46 from the English-language medical literature. Results There were 52 females and 1 male. The mean age was 53 years. Tumor size ranged from 1 to 18 cm (mean, 4.53). Axillary node metastasis was present in 61.7%. Only one patient had distant metastases at presentation. The presence of hormone receptors was reported in 24.5% of the tumors. Modified radical mastectomy was the most common surgical procedure and was performed in 50.9% of the patients. Adjuvant radiotherapy was administered to 39.6% of the patients, and 69.8% underwent chemotherapy. Thirteen percent of patients received adjuvant tamoxifen therapy. The mean follow-up was 20.75 months (range, 3–60), and 10 of 53 cases (18.9%) died of metastatic disease. Conclusions The prognosis of primary small cell carcinoma of the breast largely depends on the initial stage of the disease. Multimodality treatment including surgery, radiotherapy and chemotherapy seems to be the most appropriate strategy for early disease. Chemotherapy is usually unsuccessful in treating metastatic disease.
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Affiliation(s)
- Ozkan Kanat
- Uludag University Faculty of Medicine Department of Medical Oncology, Gorukle, Bursa
| | - Saadetin Kilickap
- Cumhuriyet University Faculty of Medicine Department of Medical Oncology, Sivas
| | - Taner Korkmaz
- Marmara University Faculty of Medicine Department of Medical Oncology, Istanbul
| | | | - Mustafa Canhoroz
- Uludag University Faculty of Medicine Department of Medical Oncology, Gorukle, Bursa
| | - Erdem Cubukcu
- Uludag University Faculty of Medicine Department of Medical Oncology, Gorukle, Bursa
| | - Sahsine Tolunay
- Uludag University Faculty of Medicine Department of Pathology, Gorukle, Bursa, Turkey
| | - Turkkan Evrensel
- Uludag University Faculty of Medicine Department of Medical Oncology, Gorukle, Bursa
| | - Osman Manavoglu
- Uludag University Faculty of Medicine Department of Medical Oncology, Gorukle, Bursa
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21
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Feffer JB, Branis NM, Albu JB. Dual Paraneoplastic Endocrine Syndromes Heralding Onset of Extrapulmonary Small Cell Carcinoma: A Case Report and Narrative Review. Front Endocrinol (Lausanne) 2018; 9:170. [PMID: 29755405 PMCID: PMC5932342 DOI: 10.3389/fendo.2018.00170] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/03/2018] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVE Extrapulmonary small cell carcinoma (EPSCC) is rare and frequent metastases at presentation can complicate efforts to identify a site of origin. In particular, SCC comprises <1% of prostate cancers and has been implicated in castration resistance. METHODS Clinical, laboratory, imaging, and pathology data are presented. RESULTS A 56-year-old man with locally advanced prostate adenocarcinoma on androgen deprivation therapy presented with a clogged nephrostomy tube. Laboratory results included calcium 13.8 mg/dL (8.5-10.5 mg/dL), albumin 3.6 g/dL (3.5-5 mg/dL), and potassium 2.8 mmol/L (3.5-5.2 mmol/L). Hypercalcemia investigation revealed intact PTH 19 pg/mL (16-87 pg/mL), 25-OH vitamin D 15.7 ng/mL (>30 ng/mL), and PTH-related peptide (PTHrP) 63.4 pmol/L (<2.3 pmol/L). Workup for hypokalemia yielded aldosterone 5.3 ng/dL (<31 ng/dL), renin 0.6 ng/mL/h (0.5-4 ng/mL/h), and 6:00 a.m. cortisol 82 µg/dL (6.7-22.6 µg/dL) with ACTH 147 pg/mL (no ref. range). High-dose Dexamethasone suppression testing suggested ACTH-dependent ectopic hypercortisolism. Contrast-enhanced CT findings included masses in the liver and right renal pelvis, a heterogeneous enlarged mass in the region of the prostate invading the bladder, bilateral adrenal thickening, and lytic lesions in the pelvis and spine. Liver biopsy identified epithelioid malignancy with Ki proliferation index 98% and immunohistochemical staining positive for synaptophysin and neuron-specific enolase, compatible with high-grade small cell carcinoma. Staining for ACTH was negative; no stain for CRH was available. Two weeks after chemotherapy, 6:00 a.m. cortisol normalized and CT scans showed universal improvement. CONCLUSION Extensive literature details paraneoplastic syndromes associated with SCC, but we report the first case of EPSCC diagnosed due to onset of dual paraneoplastic syndromes.
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22
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A Periurethral Mass in a Female Patient With Sarcoidosis. Urology 2017; 114:18-23. [PMID: 29122626 DOI: 10.1016/j.urology.2017.10.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Revised: 10/16/2017] [Accepted: 10/19/2017] [Indexed: 10/18/2022]
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23
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Qaseem Y, Fair J, Behnia S, Elojeimy S. Metachronous presentation of small-cell rectal carcinoma on an 18F-FDG PET/CT follow-up for follicular lymphoma. Radiol Case Rep 2017; 12:632-634. [PMID: 28828141 PMCID: PMC5551997 DOI: 10.1016/j.radcr.2017.04.016] [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: 02/18/2017] [Revised: 03/19/2017] [Accepted: 04/29/2017] [Indexed: 11/25/2022] Open
Abstract
We present a case of a 60-year-old woman with history of follicular lymphoma in remission presenting for an 18F-fluorodeoxyglucose positron emission tomography/computed tomography for suspected recurrence. Imaging showed widespread hypermetabolic lymphadenopathy consistent with lymphoma recurrence. A 3-month 18F-fluorodeoxyglucose positron emission tomography/computed tomography follow-up after chemotherapy showed resolution of hypermetabolic lymphadenopathy but multiple new hepatic lesions and a new subtle rectal lesion. Biopsies of both hepatic and rectal lesions revealed new diagnosis of metachronous high-grade small-cell carcinoma.
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Affiliation(s)
- Yousuf Qaseem
- Department of Radiology, University of New Mexico, MSC 10-5530, 1 University of New Mexico, Albuquerque, NM 87131, USA
| | - Joanna Fair
- Department of Radiology, University of New Mexico, MSC 10-5530, 1 University of New Mexico, Albuquerque, NM 87131, USA
| | - Sanaz Behnia
- Department of Nuclear Medicine, University of Washington, Seattle, WA, USA
| | - Saeed Elojeimy
- Department of Radiology, University of New Mexico, MSC 10-5530, 1 University of New Mexico, Albuquerque, NM 87131, USA
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24
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Noonan C, James M. A case of isolated small cell carcinoma of the brain. Acta Oncol 2017; 56:1133-1135. [PMID: 28562202 DOI: 10.1080/0284186x.2017.1290273] [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]
Affiliation(s)
- C. Noonan
- Department of Oncology, Canterbury District Health Board, Christchurch, New Zealand
| | - M. James
- Department of Oncology, Canterbury District Health Board, Christchurch, New Zealand
- Department of Medicine, University of Otago, Christchurch, New Zealand
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Yeung HM, Jeurkar C, Pompa T, Styler M. Small Cell Cancer of the Genitourinary Tract: A Case Report and Review of the Literature. Case Rep Oncol 2017; 10:489-492. [PMID: 28690522 PMCID: PMC5498951 DOI: 10.1159/000477435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Accepted: 05/11/2017] [Indexed: 12/26/2022] Open
Abstract
Small cell carcinoma of the urinary tract is an extremely rare disease with very few cases reported in the literature. Its clinical course is aggressive, and the prognosis is poor. Here, we present a case of metastatic extrapulmonary small cell carcinoma of the upper urinary tract in a 74-year-old African-American male. He initially presented with gross hematuria, 20-pound weight loss, and abdominal pain for 2 months. CT imaging showed a 14.0 × 7.0 × 16.0 cm retroperitoneal mass within the left renal fossa; biopsy revealed a carcinoma which was positive for synaptophysin and chromogranin. The patient also had detectable neuroendocrine cells in his urine cytology, confirming the diagnosis of small cell carcinoma. He was treated with carboplatin and etoposide as extrapolated from the treatment of its pulmonary counterpart. Due to the rarity of urinary tract small cell carcinoma, no randomized studies exist to guide therapy or management.
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Affiliation(s)
- Ho Man Yeung
- Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania, USA
| | - Chetan Jeurkar
- Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania, USA
| | - Tiffany Pompa
- Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania, USA
| | - Michael Styler
- Drexel University College of Medicine, Hahnemann University Hospital, Philadelphia, Pennsylvania, USA
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Azevedo D, Rios E, Vendeira L, Sarmento C. Small cell neuroendocrine carcinoma of the nasopharynx: a rare case report. Autops Case Rep 2017; 7:31-35. [PMID: 28536685 PMCID: PMC5436919 DOI: 10.4322/acr.2017.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 02/23/2017] [Indexed: 11/23/2022]
Abstract
Small cell neuroendocrine carcinoma rarely appears primarily in the head and neck and exhibits aggressive behavior with a poor prognosis. The pathologist has a significant role in the diagnosis, and a consensual treatment still does not exist. The authors report the case of a middle-aged male patient who presented repeated episodes of massive epistaxis. The diagnostic work-up disclosed the diagnosis of small cell neuroendocrine carcinoma of the nasopharynx. The patient was treated with chemotherapy followed by radiotherapy. Imaging examinations performed after the end of treatment showed apparent complete remission of the disease. The patient was kept under active surveillance with no signs of local relapse or distant metastasis after 4 years of follow-up.
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Affiliation(s)
- Daniela Azevedo
- Clinical Oncology Department, Centro Hospitalar de São João, Porto - Portugal
| | - Elisabete Rios
- Anatomic Pathology Department, Centro Hospitalar de São João, Porto - Portugal
| | - Lurdes Vendeira
- Radiation Oncology Department, Centro Hospitalar de São João, Porto - Portugal
| | - Cristina Sarmento
- Clinical Oncology Department, Centro Hospitalar de São João, Porto - Portugal
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Pytal M, Olejniczak I, Kupnicki P, Trenda-Lewy I, Michalecki Ł. The small cell carcinoma neuroendocrine type of the larynx—Case report. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.poamed.2016.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Sahai P, Baghmar S, Nath D, Arora S, Bhasker S, Gogia A, Sikka K, Kumar R, Chander S. Extrapulmonary Small Cell Carcinoma - a Case Series of Oropharyngeal and Esophageal Primary Sites Treated with Chemo-Radiotherapy. Asian Pac J Cancer Prev 2016; 16:7025-9. [PMID: 26514485 DOI: 10.7314/apjcp.2015.16.16.7025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The optimal sequence and extent of multimodality therapy remains to be defined for extrapulmonary small cell carcinoma because of its rarity. The purpose of our study was to assess the response to neoadjuvant chemotherapy followed by chemoradiation/radiation in patients with extrapulmonary small cell carcinoma. MATERIALS AND METHODS Four consecutively diagnosed patients were included in this study. The primary tumor site was oropharynx in three patients and esophagus in one. The patients with the limited disease were treated with chemotherapy followed by concurrent chemoradiation (n=2) or radiotherapy (n=1). The patient with the extensive disease with the primary site in vallecula was treated with chemotherapy and palliative radiotherapy to the metastatic site. RESULTS The median follow-up was 22.5 months (range, 8-24 months). Three patients with the limited disease (base of tongue, n=2; esophagus, n=1) were in complete remission. The patient with the extensive disease died of loco-regional tumor progression at 8 months from the time of diagnosis. CONCLUSIONS The combination of chemotherapy and radiotherapy is the preferred therapeutic approach for patients with extrapulmonary small cell carcinoma. Induction chemotherapy followed by concurrent chemoradiation or radiation provides a good loco-regional control in patients with limited disease.
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Affiliation(s)
- Puja Sahai
- Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India E-mail :
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Extrapulmonary small cell carcinoma in head and neck. The Journal of Laryngology & Otology 2015; 129 Suppl 2:S83-5. [PMID: 25706169 DOI: 10.1017/s002221511400245x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
PURPOSE The management of extrapulmonary small cell carcinoma has not been standardised to date. This study reviewed the clinical course, management and survival outcomes of patients with extrapulmonary small cell carcinoma in the head and neck region. METHODS Nine patients with extrapulmonary small cell carcinoma in the head and neck were included in this study. RESULTS Five patients received radical surgery followed by adjuvant chemotherapy or radiotherapy or both. Two other patients were treated with chemotherapy consisting of CPT11 plus cisplatin or CPT11 plus cisplatin plus VP-16 three times. Two other patients received chemoradiotherapy consisting of S-1 or CPT11 plus cisplatin. The median overall survival was 14.5 months, with a three-year survival rate of 23.7 per cent. CONCLUSIONS The prognosis of extrapulmonary small cell carcinoma is generally poor. Further prospective multicentre studies are required for better understanding of disease entities and response to treatment modalities.
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Eliyakin N, Postaci H, Baskin Y, Kozacioğlu Z. Small Cell Carcinoma of the Urinary Bladder: KIT and PDGFRA Gene Mutations. Rare Tumors 2015; 7:5982. [PMID: 26788274 PMCID: PMC4703920 DOI: 10.4081/rt.2015.5982] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2015] [Revised: 07/18/2015] [Indexed: 11/22/2022] Open
Abstract
Primary small cell carcinoma of the urinary bladder is very rare. A 72-year-old was admitted to our hospital because of hematuria and dysuria. Cystoscopy revealed a bladder full of multiple, solid and papillary tumors. Biopsies from the deep and papillary tumors were taken. Histologically, tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin, chromo-granin, synaptophysin, neuron-specific enolase, CD56, CD117 and Ki67 (labeling 70%). The tumor cells were negative for CK7, CK20, CD3, CD20, LCA, CDX2, uroplakin, thyroid transcription factor 1, PSA and p63. Metastatic workup was performed an no primary or metastatic lung lesions were noted. Due to the clinical, radiologic and immunohistochemical findings, the patient was diagnosed as primary small cell carcinoma of bladder. A molecular genetic analysis for KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes was performed, in paraffin micro dissection specimens, by the PCR-direct sequencing method. According to the sequencing analyses, two mutations were found at positions 558 (p.K558N) and 562 (p.E562D) in KIT gene exon 11 in our case. The another hand the same case presented two mutations in PDGFRA gene exon 14 at position 631 (p.P631A) and 638 (p.638Q_639AinsC). The disease process was fulminant and the patient was lost due to several complications prior to any chemotherapy.
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Affiliation(s)
- Nuket Eliyakin
- Department of Pathology, Faculty of Medicine, Adnan Menderes University, Aydin; Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir
| | - Hakan Postaci
- Departments of Pathology and Urology, Turkish Ministry of Health, Izmir Bozyaka Research and Training Hospital , Izmir, Turkey
| | - Yasemin Baskin
- Basic Oncology, Institute of Oncology, Dokuz Eylul University , Izmir
| | - Zafer Kozacioğlu
- Urology, Turkish Ministry of Health, Izmir Bozyaka Research and Training Hospital , Izmir, Turkey
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Berniker AV, Abdulrahman AA, Teytelboym OM, Galindo LM, Mackey JE. Extrapulmonary small cell carcinoma: imaging features with radiologic-pathologic correlation. Radiographics 2015; 35:152-63. [PMID: 25590395 DOI: 10.1148/rg.351140050] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Extrapulmonary small cell carcinoma (EPSCC) refers to small cell carcinoma arising outside of the lungs. EPSCC extrapulmonary small cell carcinoma is a rare aggressive neoplasm, representing a minority of all small cell carcinomas. Despite its uncommon occurrence, EPSCC extrapulmonary small cell carcinoma has been described in nearly every organ, most commonly in the gastrointestinal and genitourinary systems. As such, it is important for radiologists to be aware of the entity. Although imaging is neither sensitive nor specific for EPSCC extrapulmonary small cell carcinoma , it plays an important role by helping exclude metastases from a primary pulmonary tumor, establish tumor staging, and assess response to therapy. EPSCC extrapulmonary small cell carcinoma is diagnosed by demonstrating pathologic features of small cell carcinoma in an extrapulmonary site. There are two ways to stage EPSCC extrapulmonary small cell carcinoma . One method uses the Veterans Administration Lung Study Group system developed for small cell lung cancer that allocates patients into limited or extensive disease categories. The second approach is the American Joint Committee on Cancer tumor-node-metastasis system applied to other tumor subtypes arising from the same organ. Because of its rare and varied manifestations, the most effective treatment for EPSCC extrapulmonary small cell carcinoma has not been established. Current management recommendations are derived from retrospective studies and single-institution experiences or are extrapolated from small cell lung cancer data. Regardless of therapy, overall survival rates are poor, with 5-year survival rates around 13%. To help radiologists increase their familiarity with EPSCC extrapulmonary small cell carcinoma , this article provides (a) a background for EPSCC extrapulmonary small cell carcinoma based on the literature and (b) a pictorial review of EPSCC extrapulmonary small cell carcinoma in multiple organs, with radiologic-pathologic correlation.
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Affiliation(s)
- Abigail V Berniker
- From the Departments of Radiology (A.V.B., O.M.T., J.E.M.) and Pathology (A.A.A., L.M.G.), Mercy Catholic Medical Center, 1500 Lansdowne Ave, Darby, PA 19023
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Ahmed S, Neufeld S, Kroczak TJ, Bashir B, Ahmed N, Czaykowski P, Aljada I, Koul R, Galloway K, Drachenberg DE. Small Cell Cancer of the Bladder and Prostate: A Retrospective Review from a Tertiary Cancer Center. Cureus 2015; 7:e296. [PMID: 26261754 PMCID: PMC4529331 DOI: 10.7759/cureus.296] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 08/07/2015] [Indexed: 01/06/2023] Open
Abstract
Background: Genitourinary small cell cancer (GUSCC) is a rare malignancy. Most of the published data on how to manage this malignancy is based on institutional experience. We undertook the current retrospective review to determine the outcome of the patients with GUSCC treated at CancerCare Manitoba, Canada over a period of 18 years. Methods: The Manitoba Cancer Registry was used to identify patients with a confirmed pathological diagnosis of small cell cancer (SCC) of the bladder or prostate between January 1, 1995, and October 31, 2013. Results: There were 42 patients identified, 28 bladder SCC (17 limited, 11 extensive stage) and 14 prostate SCC (one limited, 12 extensive, and one unknown stage). The median age was 70.7 years. There were 22 patients who were treated with chemotherapy and radiation, five received radiation only, four received chemo only, nine did not receive any treatment, one patient had surgery only, and one had surgery and radiation. The median and one-year overall survival for all patients was 10.7 months and 43%. The median and one-year overall survival of SCC of the bladder was 55.1 months and 71% for the limited stage and 10.1 months and 36% for the extensive stage. The median and one-year overall survival for extensive stage SCC of the prostate was 4.1 months and 17%. There was only one patient with limited stage SCC of the prostate who did not receive any treatment and died of progressive disease 11 months from diagnosis. Conclusions: Our findings suggest that patients with limited stage SCC of the bladder can have a surprisingly good outcome with multimodality treatment. The outcome of the patients with extensive stage SCC of the bladder and prostate remains dismal and optimal therapeutic options have yet to be determined.
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Affiliation(s)
- Shahida Ahmed
- Radiation Oncology, CancerCare Manitoba, CancerCare Manitoba, University of Manitoba
| | - Sam Neufeld
- Faculty of Health Sciences, College of Medicine, University of Manitoba, Canada
| | | | - Bashir Bashir
- Radiation Oncology, CancerCare Manitoba, University of Manitoba
| | - Naseer Ahmed
- Radiation Oncology, CancerCare Manitoba, University of Manitoba
| | | | | | - Rashmi Koul
- Radiation Oncology, CancerCare Manitoba, University of Manitoba
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Xie MR, Xu SB, Sun XH, Ke L, Mei XY, Liu CQ, Ma DC. Role of surgery in the management and prognosis of limited-stage small cell carcinoma of the esophagus. Dis Esophagus 2015; 28:476-82. [PMID: 24787553 DOI: 10.1111/dote.12230] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Small cell carcinoma of the esophagus (SCCE) is a rare, highly aggressive tumor characterized by early dissemination and a poor prognosis. Surgery, chemotherapy, and radiotherapy have been used alone or in combination for the treatment of this rare disease. The aim of this retrospective study was to analyze the role of surgery in the management of limited-stage SCCE at a high-volume center. We retrospectively evaluated 73 patients with limited-stage SCCE who received an esophagectomy at our center from January 1994 to December 2011. The clinical characteristics, median survival times (MSTs), overall survival (OS), and relevant prognostic factors were analyzed. The overall MST was 23.0 months, and the 1-, 2-, 3-, and 5-year OS rates were 61.6%, 47.9%, 22.7%, and 10.6%, respectively. The MST for patients without lymph node involvement (33.0 months) was greater than the MST for patients with lymph node involvement (17.0 months) (P = 0.014). Similarly, patients who underwent radical resection had a greater MST (25.0 months) than patients who underwent palliative resection (7.0 months) (P = 0.004). Patients who received chemotherapy had a greater MST (27.0 months) than patients who did not receive chemotherapy (13.0 months) (P = 0.021). Survival analysis confirmed that a radical operation, chemotherapy, and lymph node involvement were independent prognostic factors. This study suggests that radical resection combined with chemotherapy should be recommended for patients with limited-stage SCCE, especially patients with negative regional lymph nodes. A lack of lymph node metastasis was a good prognostic factor because patients without lymph node involvement had greater OS.
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Affiliation(s)
- M R Xie
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - S B Xu
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - X H Sun
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - L Ke
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - X Y Mei
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - C Q Liu
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
| | - D C Ma
- Department of Thoracic Surgery, Anhui Provincial Hospital affiliated, Anhui Medical University, Hefei, Anhui, China
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Zeng M, Yang SD, Zhang JL, Chen XM. Primary small cell neuroendocrine carcinoma of the oral cavity: A case report and review of the literature. Oncol Lett 2015; 10:887-890. [PMID: 26622589 DOI: 10.3892/ol.2015.3298] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2014] [Accepted: 04/13/2015] [Indexed: 12/28/2022] Open
Abstract
Small cell neuroendocrine carcinoma (SNEC) of the oral cavity is a rare and distinctive tumor with aggressive clinical behavior. Thus far, only a small number of cases have been reported and no definitive standard treatment strategy has been determined. The current study reports a case of oral SNEC arising in the lower gingiva in a 73-year-old male. Computed tomography displayed a relatively well-defined mass measuring 2.8×2×1.4 cm in size. The mass was located in the buccal side of the right mandibular posterior gingiva and exhibited no bony involvement. Histopathological examination revealed a proliferation of small cells with ovoid- to spindle-shaped nuclei, fine granular chromatin, inconspicuous nucleoli, scant cytoplasm and high mitotic activity. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin and neuron-specific enolase. Surgical resection and radical neck dissection were performed prior to the administration of adjuvant chemotherapy with a combination of cisplatin and etoposide. No evidence of local recurrence or metastasis was observed at 14 months post-surgery.
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Affiliation(s)
- Ming Zeng
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei‑MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Shao-Dong Yang
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Jia-Li Zhang
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
| | - Xin-Ming Chen
- Department of Pathology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430072, P.R. China
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Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review. Diagnostics (Basel) 2015; 5:119-76. [PMID: 26854147 PMCID: PMC4665594 DOI: 10.3390/diagnostics5020119] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 03/24/2015] [Accepted: 03/26/2015] [Indexed: 02/07/2023] Open
Abstract
To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4–16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities.
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Dores GM, Qubaiah O, Mody A, Ghabach B, Devesa SS. A population-based study of incidence and patient survival of small cell carcinoma in the United States, 1992-2010. BMC Cancer 2015; 15:185. [PMID: 25885914 PMCID: PMC4378011 DOI: 10.1186/s12885-015-1188-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 03/12/2015] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND In contrast to the well-described epidemiology and behavior of small cell lung carcinoma (SCLC), little is known about extrapulmonary small cell carcinoma (EPSCC). METHODS Using data from the Surveillance, Epidemiology and End Results (SEER) Program (1992-2010), we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), annual percent change (APC), relative survival (RS), RS ratios (RSRs), and the respective 95% confidence intervals (95% CI) of SCLC and EPSCC according to primary site. We used the SEER historic stage variable that includes localized (confined to the organ of origin), regional (direct extension to adjacent organ/tissue or regional lymph nodes), and distant (discontinuous metastases) stages and combined localized and regional stages into "limited" stage. RESULTS The incidence of SCLC (IR = 76.3/million person-years; n = 51,959) was 22-times that of EPSCC (IR = 3.5; n = 2,438). Of the EPSCC sites, urinary bladder, prostate, and uterine cervix had the highest incidence (IRs = 0.7-0.8); urinary bladder (IRR = 4.91) and stomach (IRR = 3.46) had the greatest male/female disparities. Distant-to-limited stage site-specific IRRs of EPSCC were significantly elevated for pancreas (IRR = 6.87; P < 0.05), stomach, colon/rectum, ovary, and prostate (IRRs = 1.62-2.42; P < 0.05) and significantly decreased for salivary glands, female breast, uterine cervix, and urinary bladder (IRRs = 0.32-0.46). During 1992-2010, significant changes in IRs were observed for EPSCC overall (APC = 1.58), small cell carcinoma of the urinary bladder (APC = 6.75), SCLC (APC = -2.74) and small cell carcinoma of unknown primary site (APC = -4.34). Three-year RS was significantly more favorable for patients with EPSCC than SCLC for both limited (RSR = 2.06; 95% CI 1.88, 2.26) and distant stages (RSR = 1.55; 95% CI 1.16, 2.07). Among limited stage small cell carcinoma, RS was most favorable for salivary glands, female breast, and uterine cervix (RS = 52-68%), whereas RS for nearly all sites with distant stage disease was <10%. CONCLUSION EPSCC comprises a heterogeneous group of diseases that appears, at least in part, etiologically distinct from SCLC and is associated with more favorable stage-specific patient survival.
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Affiliation(s)
- Graça M Dores
- Oklahoma City Veterans Affairs Health Care System, Oklahoma City, OK, 73104, USA.
- Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
| | - Osama Qubaiah
- Hematology and Oncology Associates, St. Louis, MO, 63136, USA.
| | - Ankur Mody
- Oklahoma City Veterans Affairs Health Care System, Oklahoma City, OK, 73104, USA.
| | - Bassam Ghabach
- John Peter Smith Hospital, Fort Worth, TX, 76104, USA.
- University of North Texas Health Science Center, Fort Worth, TX, 76106, USA.
| | - Susan S Devesa
- Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
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Metastatic extrapulmonary small cell carcinoma to the cerebellopontine angle: a case report and review of the literature. Case Rep Oncol Med 2015; 2015:847058. [PMID: 25810937 PMCID: PMC4355812 DOI: 10.1155/2015/847058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 02/11/2015] [Indexed: 11/21/2022] Open
Abstract
Extrapulmonary small cell carcinomas (EPSCC) are rare malignancies with poor patient prognoses. We present the case of a 63-year-old male who underwent surgical resection of a poorly differentiated small cell carcinoma, likely from a small intestinal primary tumor that metastasized to the cerebellopontine angle (CPA). A 63-year-old male presented with mild left facial paralysis, hearing loss, and balance instability. MRI revealed a 15 mm mass in the left CPA involving the internal auditory canal consistent with a vestibular schwannoma. Preoperative MRI eight weeks later demonstrated marked enlargement to 35 mm. The patient underwent a suboccipital craniectomy and the mass was grossly different visually and in consistency from a standard vestibular schwannoma. The final pathology revealed a poorly differentiated small cell carcinoma. Postoperative PET scan identified avid uptake in the small intestine suggestive of either a small intestinal primary tumor or additional metastatic disease. The patient underwent whole brain radiation therapy and chemotherapy and at last follow-up demonstrated improvement in his symptoms. Surgical resection and radiotherapy are potential treatment options to improve survival in patients diagnosed with NET brain metastases. We present the first documented case of skull base metastasis of a poorly differentiated small cell carcinoma involving the CPA.
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Grigore AD, Ben-Jacob E, Farach-Carson MC. Prostate cancer and neuroendocrine differentiation: more neuronal, less endocrine? Front Oncol 2015; 5:37. [PMID: 25785244 PMCID: PMC4347593 DOI: 10.3389/fonc.2015.00037] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 02/03/2015] [Indexed: 12/17/2022] Open
Abstract
Neuroendocrine differentiation (NED) marks a structural and functional feature of certain cancers, including prostate cancer (PCa), whereby the malignant tissue contains a significant proportion of cells displaying neuronal, endocrine, or mixed features. NED cells produce, and can secrete, a cocktail of mediators commonly encountered in the nervous system, which may stimulate and coordinate cancer growth. In PCa, NED appears during advanced stages, subsequent to treatment, and accompanies treatment resistance and poor prognosis. However, the term “neuroendocrine” in this context is intrinsically vague. This article seeks to provide a framework on which a unified view of NED might emerge. First, we review the mutually beneficial interplay between PCa and neural structures, mainly supported by cell biology experiments and neurological conditions. Next, we address the correlations between PCa and neural functions, as described in the literature. Based upon the integration of clinical and basic observations, we suggest that it is legitimate to seek for true neural differentiation, or neuromimicry, in cancer progression, most notably in PCa cells exhibiting what is commonly described as NED.
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Affiliation(s)
- Alexandru Dan Grigore
- Department of BioSciences, Rice University , Houston, TX , USA ; Center for Theoretical Biological Physics, Rice University , Houston, TX , USA
| | - Eshel Ben-Jacob
- Center for Theoretical Biological Physics, Rice University , Houston, TX , USA ; Sackler School of Physics and Astronomy, Tel Aviv University , Tel Aviv , Israel ; Sagol School of Neuroscience, Tel Aviv University , Tel Aviv , Israel
| | - Mary C Farach-Carson
- Department of BioSciences, Rice University , Houston, TX , USA ; Center for Theoretical Biological Physics, Rice University , Houston, TX , USA ; Department of Bioengineering, Rice University , Houston, TX , USA
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Gennatas S, Noble J, Stanway S, Gunapala R, Chowdhury R, Wotherspoon A, Benepal T, Popat S. Patterns of relapse in extrapulmonary small cell carcinoma: retrospective analysis of outcomes from two cancer centres. BMJ Open 2015; 5:e006440. [PMID: 25588780 PMCID: PMC4298106 DOI: 10.1136/bmjopen-2014-006440] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
OBJECTIVES We conducted a retrospective review of patients with extrapulmonary small cell carcinomas (EPSCCs) to explore the distribution, treatments, patterns of relapse and outcomes by primary site. SETTING We have reviewed the outcomes of one of the largest data sets of consecutive patients with EPSCC identified from two major cancer centres. PARTICIPANTS Consecutive patients with a histopathological diagnosis of EPSCC from the two institutions were retrospectively identified. PRIMARY AND SECONDARY OUTCOME MEASURES Outcomes were evaluated including stage at presentation, treatments given, sites of relapse, time to distant relapse, progression-free survival and overall survival (OS). RESULTS From a total 159 patients, 114 received first-line chemotherapy, 80.5% being platinum-based. Response rate was 48%. Commonest primary sites were genitourinary and gynaecological. 44% of patients presented with metastatic disease. 55.9% relapsed with liver the commonest site, whereas only 2.5% developed brain metastases. Median OS was 13.4 months for all patients, 7.6 months and 19.5 months for those with metastatic and non-metastatic disease, respectively. Gynaecological and head and neck patients had significantly better OS compared to gastrointestinal patients. CONCLUSIONS EPSCCs demonstrate high response rates to chemotherapy and high rates of distant metastases. Primary sites may influence prognosis, and survival is optimal with a radical strategy. Brain metastases are rare and we therefore do not recommend prophylactic cranial irradiation.
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Affiliation(s)
- S Gennatas
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK
- Department of Medicine, Royal Marsden Hospital, London, UK
| | - J Noble
- Department of Medicine, Royal Marsden Hospital, London, UK
| | - S Stanway
- Department of Medicine, Royal Marsden Hospital, London, UK
| | - R Gunapala
- Department of Medicine, Royal Marsden Hospital, London, UK
| | - R Chowdhury
- Department of Medicine, Dimbleby Cancer Centre, Kings College London, London, UK
| | - A Wotherspoon
- Department of Histopathology, Royal Marsden Hospital, London, UK
| | - T Benepal
- Department of Oncology, St George's Hospital, London, UK
| | - S Popat
- Faculty of Medicine, National Heart and Lung Institute, Imperial College London, London, UK
- Department of Medicine, Royal Marsden Hospital, London, UK
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Lee SW, Lim KT, Bae DS, Park SY, Kim YT, Kim KR, Nam JH. A multicenter study of the importance of systemic chemotherapy for patients with small-cell neuroendocrine carcinoma of the uterine cervix. Gynecol Obstet Invest 2014; 79:172-8. [PMID: 25500455 DOI: 10.1159/000367920] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Accepted: 08/27/2014] [Indexed: 11/19/2022]
Abstract
AIMS We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. METHODS We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. RESULTS Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. CONCLUSIONS SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.
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Affiliation(s)
- Shin-Wha Lee
- Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan, Seoul, Korea
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Satoh T, Takei Y, Treilleux I, Devouassoux-Shisheboran M, Ledermann J, Viswanathan AN, Mahner S, Provencher DM, Mileshkin L, Åvall-Lundqvist E, Pautier P, Reed NS, Fujiwara K. Gynecologic Cancer InterGroup (GCIG) consensus review for small cell carcinoma of the cervix. Int J Gynecol Cancer 2014; 24:S102-8. [PMID: 25341572 DOI: 10.1097/igc.0000000000000262] [Citation(s) in RCA: 81] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Small cell carcinoma of the cervix (SCCC) is a rare histological entity of uterine cervical cancer. Compared with other common histological types, squamous cell carcinoma or adenocarcinoma, the outcome of SCCC is poor because of the high incidence of nodal or distant metastasis even with early stage. In this review, current consensus of epidemiology, pathology, and initial treatment for SCCC will be discussed.
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Affiliation(s)
- Toyomi Satoh
- *University of Tsukuba, Tsukuba-City, Japan and GOTIC; †Jichi Medical University, Shimono-City, Japan and GOTIC; ‡Centre Leon Berard, Lyon, France and GINECO; §Hospices Civils de Lyon, France and GINECO; ∥University College of London, London, UK and NCRI/MRC; ¶Harvard Medical School, Boston, MA and RTOG; #Universtatsklinikum Hamburg-Eppendorf, Hamburg, Germany and AGO; **University of Montreal, Montreal, Quebec, Canada and NCIC-GCT; ††Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia and ANZGOG; ‡‡Karolinska Institute, Stockholm, Sweden and NSGO; §§Insitut Gustave Roussy, Villejuif, France and GINECO; ∥∥Beatson Oncology Centre, Glasgow, UK and EORTC; and ¶¶Saitama Medical University International Medical Center, Hidaka-City, Japan and GOTIC
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Fisher CA, Harms PW, McHugh JB, Edwards PC, Siddiqui J, Palanisamy N, Bichakjian CK, Benavides E, Danciu TE. Small cell carcinoma in the parotid harboring Merkel cell polyomavirus. Oral Surg Oral Med Oral Pathol Oral Radiol 2014; 118:703-12. [PMID: 25457888 DOI: 10.1016/j.oooo.2014.09.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 09/08/2014] [Accepted: 09/10/2014] [Indexed: 12/14/2022]
Abstract
OBJECTIVE This study aimed to document three new cases of primary small cell carcinoma (SmCC) of the parotid and examine immunohistochemical and quantitative real-time polymerase chain reaction (qPCR) data of the recently developed Merkel cell polyomavirus (MCPyV) within these tumors. STUDY DESIGN Immunohistochemistry for neuroendocrine markers (chromogranin A, CD56, CD57, neuron-specific enolase [NSE], thyroid transcription factor 1 [TTF-1]), epithelial markers (CK20, CK7, CAM 5.2), and MCPyV large T antigen (LTAg) were examined. qPCR and Sanger sequencing were performed to confirm the presence of the MCPyV LTAg gene. RESULTS Two males and one female, average age 76 years, presented with left parotid masses. Clinical examinations, histories, and imaging studies were negative for cutaneous Merkel cell carcinoma (MCC), pulmonary and extrapulmonary SmCC, or any other malignancy. Immunohistochemical analysis demonstrated positive immunoreactivity for CK20 in a perinuclear dotlike pattern (3/3), CAM 5.2 (3/3), (2/3), NSE (3/3), CD56 (2/3), and CD57 (3/3). Two cases stained positive for MCPyV, showing moderate to strong, diffuse positivity, confirmed with qPCR. PCR-Sanger sequencing of LTAg exon 2 showed greater than 97% similarity to the MCPyV reference genome in both cases. CONCLUSION Our findings expand the number of reported cases classified as primary parotid SmCC that harbors MCPyV and underscore the similarity between cutaneous MCC and parotid SmCC. Further investigation is needed to determine whether immune-based therapeutic strategies targeting MCPyV in MCC are also effective in the setting of parotid SmCC harboring MCPyV.
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Affiliation(s)
| | - Paul W Harms
- Department of Pathology, University of Michigan Health System, Ann Arbor, MI; Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI
| | - Jonathan B McHugh
- Department of Pathology, University of Michigan Health System, Ann Arbor, MI
| | - Paul C Edwards
- School of Dentistry, Indiana University, Indianapolis, IN
| | - Javed Siddiqui
- Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI
| | - Nallasivam Palanisamy
- Michigan Center for Translational Pathology, University of Michigan Health System, Ann Arbor, MI
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Yamaguchi T, Machida N, Morizane C, Kasuga A, Takahashi H, Sudo K, Nishina T, Tobimatsu K, Ishido K, Furuse J, Boku N, Okusaka T. Multicenter retrospective analysis of systemic chemotherapy for advanced neuroendocrine carcinoma of the digestive system. Cancer Sci 2014; 105:1176-81. [PMID: 24975505 PMCID: PMC4462387 DOI: 10.1111/cas.12473] [Citation(s) in RCA: 175] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 06/11/2014] [Accepted: 06/24/2014] [Indexed: 12/14/2022] Open
Abstract
This study analyzed outcomes of systemic chemotherapy for advanced neuroendocrine carcinoma (NEC) of the digestive system. Clinical data from 258 patients with unresectable or recurrent NEC of the gastrointestinal tract (GI) or hepato-biliary-pancreatic system (HBP), who received chemotherapy, were collected from 23 Japanese institutions and analyzed retrospectively. Patients had primary sites in the esophagus (n = 85), stomach (n = 70), small bowel (n = 6), colorectum (n = 31), hepato-biliary system (n = 31) and pancreas (n = 31). Median overall survival (OS) was 13.4 months the esophagus, 13.3 months for the stomach, 29.7 months for the small bowel, 7.6 months for the colorectum, 7.9 months for the hepato-biliary system and 8.5 months for the pancreas. Irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were most commonly selected for GI-NEC and HBP-NEC. For patients treated with IP/EP (n = 160/46), the response rate was 50/28% and median OS was 13.0/7.3 months. Multivariate analysis among patients treated with IP or EP showed that the primary site (GI vs HBP; hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35-0.97) and baseline serum lactate dehydrogenase levels (not elevated vs elevated; HR 0.65, 95% CI 0.46-0.94) were independent prognostic factors for OS, while the efficacy of IP was slightly better than for EP (HR 0.80, 95% CI 0.48-1.33; P = 0.389). IP and EP are the most common treatment regimens for NEC of the digestive system. HBP primary sites and elevated lactate dehydrogenase levels are unfavorable prognostic factors for survival. A randomized controlled trial is required to establish the appropriate chemotherapy regimen for advanced NEC of the digestive system. This study was registered at UMIN as trial number 000005176.
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Affiliation(s)
- Tomohiro Yamaguchi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center HospitalTokyo, Japan
- Department of Biostatics and Epidemiology, Graduate School of Medicine, Yokohama City UniversityKanagawa, Japan
| | - Nozomu Machida
- Division of Gastrointestinal Oncology, Shizuoka Cancer CenterShizuoka, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center HospitalTokyo, Japan
| | - Akiyoshi Kasuga
- Hepatobiliary and Pancreatic Division, Cancer Institute HospitalTokyo, Japan
| | - Hideaki Takahashi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital EastChiba, Japan
| | - Kentaro Sudo
- Division of Gastrointestinal Oncology, Chiba Cancer CenterChiba, Japan
| | - Tomohiro Nishina
- Department of Gastrointestinal Medical Oncology, Shikoku Cancer CenterEhime, Japan
| | | | - Kenji Ishido
- Department of Gastroenterology, Kitasato University School of MedicineKanagawa, Japan
| | - Junji Furuse
- Department of Medical Oncology, Kyorin University School of MedicineTokyo, Japan
| | - Narikazu Boku
- Department of Clinical Oncology, St. Marianna University School of MedicineKanagawa, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center HospitalTokyo, Japan
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Extrapulmonary small cell carcinoma: the University of Kansas experience and review of literature. Med Oncol 2014; 31:187. [PMID: 25151532 DOI: 10.1007/s12032-014-0187-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 08/13/2014] [Indexed: 01/12/2023]
Abstract
Though extrapulmonary small cell carcinoma was first described over 80 years ago, definitive treatment recommendations are lacking. The treatment strategies commonly utilized are extrapolated from pulmonary small cell carcinoma experience. A better understanding of this entity is needed to improve management approach. The University of Kansas tumor registry was reviewed from 1990 to 2013. Thirty-five cases met the inclusion and exclusion criteria for review. Age, gender, smoking status, weight loss, metastatic disease-related data, stage, performance status (PS), treatment received, and survival data were collected. Patients were evaluated with a variety of primary locations of disease including GI tract (29%), GU tract (35%), Gyn organs (17%), head and neck (14%), and unknown primary (9%). Several sites of metastatic disease were noted, with 57 and 43% of patients meeting criteria for limited disease (LD) and extensive disease (ED), respectively. Chemotherapy, surgery, and radiation were used in several different regimens, with small cell lung cancer-type regimens incorporating a platinum and etoposide being the most common (74%). Patients with LD had a median survival of 36 months compared with 5 months in patients with ED (p<0.0001). Among different primary sites, patients with GU and Gyn LD tumors had best median survival of 36 months. Among other variables that were examined with respect to their poor prognostic significance, PS>2 (p=0.001) and one or fewer number of treatment modalities especially in LD (p=0.0005) were found to be associated significantly with mortality. GI and GU tract tumors were the most common primary sites of disease in our retrospective review. Survival varied according to stage, PS, site of primary disease, use of chemotherapy, and number of treatment modalities used. Further studies are needed to better understand this rare disorder and optimize management approach.
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Bezerra SM, Lotan TL, Faraj SF, Karram S, Sharma R, Schoenberg M, Bivalacqua TJ, Netto GJ. GATA3 expression in small cell carcinoma of bladder and prostate and its potential role in determining primary tumor origin. Hum Pathol 2014; 45:1682-7. [DOI: 10.1016/j.humpath.2014.04.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Revised: 04/04/2014] [Accepted: 04/09/2014] [Indexed: 11/15/2022]
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Yazıcı O, Ozdemir NY, Sendur MAN, Aksoy S, Zengin N. Current approaches for prophylactic cranial irradiation in extrapulmonary small cell carcinoma. Curr Med Res Opin 2014; 30:1327-36. [PMID: 24628530 DOI: 10.1185/03007995.2014.904771] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Small cell lung cancer (SCLC) patients, who have achieved complete or partial response after chemotherapy, should be followed with prophylactic cranial irradiation (PCI). PCI for extrapulmonary small cell carcinoma (EPSCC) is not routinely recommended. The purpose of this review is to discuss all aspects of PCI in management of EPSCC. SCOPE The PubMed database and the database of online abstracts of the American Society of Oncology (ASCO), ASCO Genitourinary (GU) Cancers meetings and clinical trials were searched up to 15 October 2013 using the following search keywords: 'SCC or EPSCC of each organ site and prophylactic cranial radiotherapy'. The language of screened abstracts and manuscripts was limited to English. The papers which included the largest case series and data of cases about prophylactic cranial radiotherapy and/or were published in the last 10 years were selected. FINDINGS Many single center studies showed low incidence of brain metastasis in patients with esophageal small cell carcinoma (SCC). Due to the low incidence of brain metastasis, PCI is not recommended for esophageal SCC. Genitourinary, colorectal, small bowel and appendix cranial metastatic SCCs are extremely rare. Therefore, PCI is not recommended. The frequency of brain metastasis of prostate small cell carcinoma is much higher (16-19%) compared to other counterparts of EPSCC. PCI can be performed in selected cases of prostate SCC. High rates (41%) of brain metastasis develop in head and neck SCC. PCI should be considered for patients with head neck SCC. CONCLUSION In the literature, the brain metastasis incidence of EPSCC might vary from 1.7% up to 40%. In many patients with ESPCC, PCI is not recommended. However, we have to keep in mind that primary head and neck and prostate SCC are exceptions due to the high incidence of cranial metastasis; PCI should be recommended for these patients on an individual basis.
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Affiliation(s)
- Ozan Yazıcı
- Ankara Numune Education and Research Hospital , Ankara , Turkey
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Koga F, Yokoyama M, Fukushima H. Small cell carcinoma of the urinary bladder: a contemporary review with a special focus on bladder-sparing treatments. Expert Rev Anticancer Ther 2014; 13:1269-79. [PMID: 24168010 DOI: 10.1586/14737140.2013.851605] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Small cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive disease. To date, no standard treatment has been proposed due to the lack of prospective studies resulting from the rarity of this disease. Recently published studies of relatively large patient cohorts, however, have shed some light on the management of SCCUB patients. In this article, the authors review the epidemiology, pathogenesis, diagnosis and treatment (based on disease stage), and they then discuss the optimal therapeutic strategy for SCCUB patients, particularly for those with limited, locoregional disease. The authors conclude that multidisciplinary approaches are needed for the optimal management of this aggressive disease. The authors also discuss bladder-sparing approaches for SCCUB patients, compared to those for conventional bladder urothelial carcinoma patients.
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Should patients with extrapulmonary small-cell carcinoma receive prophylactic cranial irradiation? J Thorac Oncol 2014; 8:1215-21. [PMID: 23945390 DOI: 10.1097/jto.0b013e31829f6b03] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Extrapulmonary small-cell carcinoma (EPSCC) is a rare disease. Management is based on small-cell lung carcinoma. Prophylactic cranial irradiation (PCI) is not routinely administered in EPSCC. This study investigates the role of PCI in EPSCC, by analyzing the incidence, treatment, and survival of patients with brain metastases in a national cohort. Disease biology and epidemiology are also investigated. METHODS Patients diagnosed with primary EPSCC from the National Cancer Registry of Ireland from 1995 to 2007 were identified. The number of patients who developed brain metastases, their survival, and treatment data were documented. Patients who received PCI were investigated. Patient and disease characteristics, treatment, and survival data were stratified by stage and primary site. RESULTS Two hundred eighty patients were identified; 141 (50.4%) were men and 139 (49.6%) were women. One hundred eighty six patients (66.4%) had extensive-stage disease, 65 (23.2%) had limited-stage disease, and in 29 patients (10.3%) the stage was unknown. Eighteen patients (6.4%) developed brain metastases, with a median overall survival of 10.1 months. Eleven (61%) received cranial irradiation, and 12 (67%) received palliative chemotherapy. Two patients in the entire cohort (0.17%) received PCI. The most common primary sites included the esophagus (n = 43; 15.4%), cervix uteri (n = 17; 6.0%), bladder (n = 13; 4.6%), and prostate (n = 10; 3.6%). Median overall survival was 15.2 months (10.2-20.6) for limited-stage disease, 2.3 months (1.7-3.1) for extensive-stage EPSCC, and 3.7 months (1.3-8.3) for disease of unknown stage. CONCLUSION Brain metastases were uncommon in EPSCC compared with small-cell lung carcinoma. PCI is thus probably not warranted in this disease.
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Matt L, Limjoco T, Sehgal R. A Case of Small Cell Cancer of the Breast in a Male with Synchronous Stage IV Non-Small Cell Lung Carcinoma. Rare Tumors 2013; 5:e52. [PMID: 24179664 PMCID: PMC3804827 DOI: 10.4081/rt.2013.e52] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2013] [Revised: 08/03/2013] [Accepted: 08/05/2013] [Indexed: 11/23/2022] Open
Abstract
Extrapulmonary small cell carcinomas (EPSCC) are extremely rare. Most reports indicate success with therapy directed at the tumor as if it was pulmonary small cell carcinoma Primary small cell carcinoma of the breast is an uncommon form of EPSCC. Differentiating between a primary small cell carcinoma of the breast from metastatic disease to the breast is very important. According to the literature, there have been approximately 70 cases reported worldwide. Of these cases, only two cases are documented in men. Prognosis is varied and depends on stage of disease at presentation. A combination of surgery, chemotherapy and/or radiation is required to adequately treat patients with small cell carcinoma of the breast. We present a case of a male patient diagnosed with stage IV non-small cell lung carcinoma first and then subsequently diagnosed with a concurrent small cell carcinoma of the breast responding to treatment with concurrent chemotherapy and radiation.
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Affiliation(s)
- Laurie Matt
- Department of Hematology/Oncology, Edwards Comprehensive Cancer Center, Cabell Huntington Hospital , Huntington, WV
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