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Rotaru V, Chitoran E, Mitroiu MN, Ionescu SO, Neicu A, Cirimbei C, Alecu M, Gelal A, Prie AD, Simion L. Intestinal Clear Cell Sarcoma-A Case Presentation of an Extremely Rare Tumor and Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:847. [PMID: 38929464 PMCID: PMC11205295 DOI: 10.3390/medicina60060847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 05/16/2024] [Accepted: 05/20/2024] [Indexed: 06/28/2024]
Abstract
Background: Clear cell sarcoma (CCS) is an extremely rare form of sarcoma representing less than 1% of all soft-tissue sarcomas. It has morphological, structural, and immunohistochemical similarities to malignant melanoma, affecting young adults and equally affecting both sexes, and is usually located in the tendinous sheaths and aponeuroses of the limbs. Gastrointestinal localization is exceptional, with less than 100 cases reported thus far. The gene fusion of activating transcription factor 1 (ATF1) and the Ewing sarcoma breakpoint region 1 (EWSR1) are pathognomonic for clear cell sarcoma, representing the key to the diagnosis. CCS is an extremely aggressive tumor, with >30% having distant or lymphatic metastasis at the time of diagnostic, and it has a high recurrence rate of over 80% in the first year after diagnosis and a high tendency for metastatic dissemination. Given the rarity of this tumor, there is no standardized treatment. Early diagnosis and radical surgery are essential in the treatment of CCS both for the primary tumor and for recurrence or metastasis. Chemo-radiotherapy has very little effect and is rarely indicated, and the role of targeted therapies is still under investigation. Case presentation: We present an extremely rare case of intestinal CSS in a 44-year-old Caucasian female. The patient, asymptomatic, first presented for a routine checkup and was diagnosed with mild iron-deficiency anemia. Given her family history of multiple digestive cancers, additional investigations were requested (gastroscopy, colonoscopy, tumoral markers and imaging) and the results were all within normal limits. In the subsequent period, the patient experienced mild diffuse recurrent abdominal pain, which occurred every 2-3 months. Two years later, the patient presented with symptoms of intestinal obstruction and underwent an emergency laparotomy followed by segmental enterectomy and regional lymphadenectomy for stenotic tumor of the jejunum. Histology, immunohistochemistry, and genetic testing established the diagnosis of CCS. No adjuvant therapy was indicated. Initially, no signs of recurrence or metastasis were detected, but after 30 and 46 months, respectively, from the primary treatment, the patient developed liver metastasis and pericolic peritoneal implants treated by atypical hepatic resections and right hemicolectomy. The patient remains under observation.
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Affiliation(s)
- Vlad Rotaru
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Elena Chitoran
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Madalina Nicoleta Mitroiu
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Sinziana Octavia Ionescu
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Ariana Neicu
- Pathology Department, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Ciprian Cirimbei
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Mihnea Alecu
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Aisa Gelal
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Andra Delia Prie
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
| | - Laurentiu Simion
- General Surgery Department 10, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- General Surgery and Surgical Oncology Department I, Bucharest Institute of Oncology “Prof. Dr. Al. Trestioreanu”, 022328 Bucharest, Romania
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Huang WP, Li LM, Gao JB. Postoperative multiple metastasis of clear cell sarcoma-like tumor of the gastrointestinal tract in adolescent: A case report. World J Clin Cases 2022; 10:6175-6183. [PMID: 35949819 PMCID: PMC9254186 DOI: 10.12998/wjcc.v10.i18.6175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 11/25/2021] [Accepted: 04/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant gastrointestinal mesenchymal soft tissue tumor. Its genetic feature is EWSR1 gene rearrangement. Histologically, it is often accompanied by a varying number of CD68-positive osteoclast-like giant cells. CCSLGT mostly occurs in the small intestinal wall of young people and children. In terms of clinical manifestations, there is no significant difference between it and other gastrointestinal tumors, and the diagnosis depends on immunohistochemistry and gene detection.
CASE SUMMARY A 16-year-old man developed dizziness and fatigue 2 mo ago, and 10 d ago showed progressive exacerbation of paroxysmal epigastric pain and stopped flatulence and defecation. Computed tomography showed a soft tissue mass in the distal ileum. After complete resection of the lesion, it was diagnosed by combined immunohistochemical and genetic examination as CCSLGT. After surgery, the patient gradually developed lymph node, liver, lung, bone, left thigh, pleura and adrenal metastasis. The survival time was 4 years and 8 mo.
CONCLUSION Whole abdominal computed tomography enhancement is recommended for patients with gastrointestinal symptoms. There is no effective treatment for CCSLGT with multiple metastases via the lymphatic system and bloodstream after surgical resection.
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Affiliation(s)
- Wen-Peng Huang
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Li-Ming Li
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Jian-Bo Gao
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
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Malignant Gastrointestinal Neuroectodermal Tumour-Case Report with Review of Literature. J Gastrointest Cancer 2021; 52:1125-1130. [PMID: 33523361 DOI: 10.1007/s12029-020-00575-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2020] [Indexed: 12/22/2022]
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Zhu P, Zhang T, Bi K, Wu Y, Chen X, Zhang H, Huang D, Zhang L, Zeng Y, Yi X. Primary Clear Cell Sarcoma of the Ileum: A Case Report With Next-Generation Sequencing Analysis. Int J Surg Pathol 2021; 29:677-684. [PMID: 33412984 DOI: 10.1177/1066896920985311] [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: 11/16/2022]
Abstract
As the concept of clear cell sarcoma-like tumor or malignant gastrointestinal neuroectodermal tumor (CCS-LT/MGNET) has been widely accepted, primary CCS of the gastrointestinal tract (CCS-GI) is becoming a rare entity. In this article, we describe a case of primary CCS-GI that occurred in the ileum of a 65-year-old male to further illustrate its rare occurrence. Similar to CCS of soft tissue (CCS-ST), the tumor was composed of spindled to epithelioid cells displaying fascicular, nested, or pseudopapillary arrangement. The tumor cells had large round to ovoid nuclei with vesicular chromatin and prominent nucleoli, containing eosinophilic to pale cytoplasm. In contrast to CCS-LT/MGNET, immunohistochemical study also showed variable positivity of HMB45, melan A, and MiTF besides the strong and diffuse staining of S100 protein and SOX10. Fluorescence in situ hybridization (FISH) using fusion probes identified EWSR1 and ATF1 genes rearrangement. Next-generation sequencing (NGS) analysis further revealed EWSR1 exons9/8-ATF1 exon4 and ATF1 exon3- EWSR1 exon11 fusion genes. CCS-GI and CCS-LT/MGNET possibly represent 2 related entities of the same spectrum, which differentiate along 2 different pathways.
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Affiliation(s)
- Peipei Zhu
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tingting Zhang
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ke Bi
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yunjin Wu
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xue Chen
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Haoyang Zhang
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Dandan Huang
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Long Zhang
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yu Zeng
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xianghua Yi
- Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
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Okada T, Hirano Y, Ishikawa S, Kondo H, Ishii T, Yamaguchi S. A long-term survivor of clear cell sarcoma-like tumor of the gastrointestinal tract with liver metastasis: a case report. Surg Case Rep 2020; 6:260. [PMID: 33025168 PMCID: PMC7538498 DOI: 10.1186/s40792-020-01028-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/23/2020] [Indexed: 01/10/2023] Open
Abstract
Background Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLTGT) is extremely rare. It is a mesenchymal neoplasm that usually forms in the small intestine of adolescents and young adults, is prone to local recurrence and metastasis, and has a high mortality rate. We report a patient with CCSLTGT with lymph node- and liver metastases, who continues to survive 6 years after initial surgical resection. Case presentation A 38-year-old woman presented with lightheadedness. Laboratory analysis revealed anemia (hemoglobin, 6.7 g/dL), and enhanced computed tomography (CT) demonstrated a mass in the small intestine, about 6 cm in diameter, with swelling of 2 regional lymph nodes. Double-balloon small intestine endoscopic examination revealed a tumor accompanied by an ulcer; the biopsy findings suggested a primary cancer of the small intestine. She was admitted, and we then performed a laparotomy for partial resection of the small intestine with lymph node dissection. Pathologic examination revealed CCSLTGT with regional lymph node metastases. About 3 years later, follow-up CT revealed a single liver metastasis. Consequently, she underwent a laparoscopic partial liver resection. Histopathologic examination confirmed that the liver metastasis was consistent with CCSLTGT. It has now been 3 years without a recurrence. Conclusion Repeated radical surgical resection with close follow-up may be the only way to achieve long-term survival in patients with CCLSTGT.
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Affiliation(s)
- Takuhisa Okada
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan. .,Department of General Surgical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-Machi, Maebashi-City, Gunma-Pref, 371-8511, Japan.
| | - Yasumitsu Hirano
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan
| | - Shintaro Ishikawa
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan
| | - Hiroka Kondo
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan
| | - Toshimasa Ishii
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan
| | - Shigeki Yamaguchi
- Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, 1397-1, Yamane, Hidaka-City, Saitama-Pref, 350-1298, Japan
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Askan G, Kombak FE, Seven IE, Basturk O. Clear Cell Sarcoma-Like Tumor of the Gastrointestinal Tract. J Gastrointest Cancer 2020; 50:651-656. [PMID: 29623567 DOI: 10.1007/s12029-018-0069-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Gokce Askan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA
| | - Faruk Erdem Kombak
- Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey
| | - Ipek Erbarut Seven
- Department of Pathology, Marmara University School of Medicine, Istanbul, Turkey
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.
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Green C, Spagnolo DV, Robbins PD, Fermoyle S, Wong DD. Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. Pathology 2018; 50:490-498. [PMID: 29970252 DOI: 10.1016/j.pathol.2018.05.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/02/2018] [Accepted: 05/08/2018] [Indexed: 12/18/2022]
Abstract
Clear cell sarcoma is an uncommon sarcoma which rarely occurs as a primary tumour in the gastrointestinal tract (CCS-GIT). It shares common molecular genetic abnormalities with the more recently described entity, malignant gastrointestinal neuroectodermal tumour (GNET) but is distinguished by its morphological and immunohistochemical findings. The exact nosological relationship between these tumours continues to be debated. In this review, we present two cases of these rare neoplasms from our files and perform a statistical comparison of all published cases to determine if significant differences exist in their clinicopathological features and biological behaviour. Thirteen cases of CCS-GIT and 58 of GNET were included. CCS-GIT occurred more commonly in males (84.6% vs 46.6%, p = 0.01) and in an older age group (median 57 vs 33 years, p < 0.01). There was no significant difference in their location in the gastrointestinal tract, median tumour size and proportion of cases with an EWSR1-ATF1 vs EWSR1-CREB1 fusion. Median survival for CCS-GIT was 13.5 months and for GNET, 9.5 months (p = 0.78). There was no significant difference in the Kaplan-Meier survival curves for either time to first metastasis (p = 0.88) or overall survival (p = 0.18), including after controlling for tumour size using regression models. Our analysis confirms that aside from morphological variations between these tumours, they also exhibit epidemiological and clinical differences. Despite the prevalent perception that GNET is associated with a more aggressive clinical course, our findings indicate that there is no significant difference in their biological behaviour, although both clearly share a bleak prognosis. Further experience is awaited to determine optimal treatment strategies and whether CCS-GIT and GNET would differ in their response to various therapies.
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Affiliation(s)
- Celia Green
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia
| | - Dominic V Spagnolo
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia
| | - Peter D Robbins
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia
| | - Soraya Fermoyle
- Anatomical Pathology, PathWest Laboratory Medicine, Fiona Stanley Hospital, Murdoch, WA, Australia
| | - Daniel D Wong
- Anatomical Pathology, PathWest Laboratory Medicine, QEII Medical Centre, Nedlands, WA, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia.
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Keditsu KK, Patkar S, Bal M, Shrikhande SV, Goel M. Gastrointestinal Neuroectodermal Tumor: a Diagnostic Dilemma. Indian J Surg 2017; 79:166-168. [PMID: 28442847 PMCID: PMC5386943 DOI: 10.1007/s12262-016-1499-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 04/28/2016] [Indexed: 10/21/2022] Open
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET), a rare soft tissue sarcoma, is a recently described distinct clinicopathological entity. With only a few cases reported in literature till date, there is limited knowledge about the behavior as well as diagnosis of this tumor. GNET mimics several other tumors and hence presents as a diagnostic challenge to clinicians and pathologists alike. We report a case of gastrointestinal neuroectodermal tumors with liver metastasis.
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Affiliation(s)
- Keduovinuo K. Keditsu
- Department of GI and HPB services, Surgical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai, 400012 India
| | - Shraddha Patkar
- Department of GI and HPB services, Surgical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai, 400012 India
| | - Munita Bal
- Department of Pathology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai, 400012 India
| | - Shailesh V. Shrikhande
- Department of GI and HPB services, Surgical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai, 400012 India
| | - Mahesh Goel
- Department of GI and HPB services, Surgical Oncology, Tata Memorial Hospital, Dr. Ernest Borges Road, Parel, Mumbai, 400012 India
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Su H, Liu WS, Ren WH, Wang P, Shi L, Zhou HT. Multiple clear-cell sarcomas of small intestine with parotid gland metastasis: A case report. World J Gastroenterol 2017; 23:2258-2265. [PMID: 28405155 PMCID: PMC5374139 DOI: 10.3748/wjg.v23.i12.2258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 01/23/2017] [Accepted: 02/16/2017] [Indexed: 02/06/2023] Open
Abstract
Clear-cell sarcoma is a rare, malignant soft tissue tumor that displays melanocytic differentiation with a distinct molecular profile. It is rarely localized in the gastrointestinal tract. Herein we reported a case of multiple synchronous clear-cell sarcomas of the gastrointestinal tract with parotid gland metastasis. A 51-year-old male patient presented with a growing painless mass under the right ear. A preoperative positron emission tomography/computed tomography showed multiple intestinal masses and a mass in the right parotid with increased glucose uptake, and he underwent operative treatment with resection of three tumors in the jejunum and ileum and then received a right parotidectomy. Postoperative pathological examination showed that cells in the intestinal tumor were consistent with clear-cell sarcoma of the gastrointestinal tract, and the malignant cells in the parotid gland were similar to the intestinal tumor. Immunohistochemical studies revealed positive expression of HMB-45, Melan-A, and S-100. EWSR1 gene fusion transcripts were undetectable by fluorescence in situ hybridization.
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Primary mediastinal clear cell sarcoma: a case report and review of the literature. Diagn Pathol 2017; 12:5. [PMID: 28086809 PMCID: PMC5237244 DOI: 10.1186/s13000-016-0594-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 12/23/2016] [Indexed: 11/17/2022] Open
Abstract
Background Clear cell sarcoma (CCS) is a rare malignant soft-tissue neoplasm that displays melanocytic markers and exhibits striking histopathological features. The tumour has a predilection for the lower extremities and rarely presents in the mediastinum. Case presentation We present a case of primary mediastinal CCS in a 57-year-old man. Computer tomography (CT) revealed a 12 × 12 × 7.5 cm mass in the anterior mediastinum. Microscopically, the tumour mainly consisted of epithelioid cells with oval vesicular nuclei and eosinophilic cytoplasm. Immunohistochemically, the tumour was positive for human melanoma black 45 (HMB-45) and vimentin but negative for S-100 and Melan-A. Fluorescence in situ hybridisation (FISH) showed a translocation involving the EWSR1 gene region. Conclusion This report will illustrate that the mediastinum is a potential site for primary CCS and FISH plays an important role in making a conclusive diagnosis.
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Simultaneous Clear Cell Sarcomas of the Duodenum and Jejunum. Case Rep Med 2016; 2016:1534029. [PMID: 27375743 PMCID: PMC4914738 DOI: 10.1155/2016/1534029] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Accepted: 05/18/2016] [Indexed: 02/08/2023] Open
Abstract
Clear cell sarcoma (CCS) is an uncommon tumor that usually presents as an extremity mass but can rarely manifest as a gastrointestinal tumor with a diverse spectrum of symptoms, most commonly related to a mass effect or ulceration. Herein we report a case in which two separate tumors, one in the duodenum and the other in the jejunum, present concurrently. The subject presented with symptomatic anemia and underwent imaging and endoscopic studies that culminated in the discovery of the two lesions. He subsequently underwent operative treatment with resection of both tumors and made an unremarkable recovery. The resection specimen consisted of two separate clear cell sarcomas with negative margins. Under microscopic evaluation, they demonstrated nested growths of epithelioid cells with scattered spindled cells infiltrating the enteric wall. The neoplastic cells were positive for S100 with scattered expression of Melan A. Florescence in situ hybridization revealed a translocation at the EWRS1 locus. He was disease-free for 30 months following the procedure; then he developed a rapidly progressing metastatic disease with subsequent death 4 months later.
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Insabato L, Guadagno E, Natella V, Somma A, Bihl M, Pizzolorusso A, Mainenti PP, Apice G, Tornillo L. An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma. Pathol Res Pract 2015; 211:688-92. [PMID: 26163185 DOI: 10.1016/j.prp.2015.06.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 06/04/2015] [Accepted: 06/05/2015] [Indexed: 12/27/2022]
Abstract
Very recently a new designation of "Malignant Neuroectodermal Gastrointestinal Tumor" has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as "clear cell sarcoma-like tumors of the gastrointestinal tract", these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities.
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Affiliation(s)
- Luigi Insabato
- Dip. Scienze Biomorfologiche e Chirurgiche, Università Federico II Napoli, Italy.
| | - Elia Guadagno
- Dip. Scienze Biomorfologiche e Chirurgiche, Università Federico II Napoli, Italy
| | - Valentina Natella
- Dip. Scienze Biomorfologiche e Chirurgiche, Università Federico II Napoli, Italy
| | - Anna Somma
- Dip. Scienze Biomorfologiche e Chirurgiche, Università Federico II Napoli, Italy
| | - Michel Bihl
- Department of Pathology, University Hospital of Basel, Switzerland
| | - Antonio Pizzolorusso
- SSD Oncologia medica Sarcomi dei Tessuti molli e delle Ossa, Istituto Tumori, Fondazione G. Pascale, Naples, Italy
| | - Pier Paolo Mainenti
- Dip. Scienze Biomorfologiche e Chirurgiche, Università Federico II Napoli, Italy
| | - Gaetano Apice
- SSD Oncologia medica Sarcomi dei Tessuti molli e delle Ossa, Istituto Tumori, Fondazione G. Pascale, Naples, Italy
| | - Luigi Tornillo
- Department of Pathology, University Hospital of Basel, Switzerland
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Kong J, Li N, Wu S, Guo X, Gu C, Feng Z. Malignant gastrointestinal neuroectodermal tumor: A case report and review of the literature. Oncol Lett 2014; 8:2687-2690. [PMID: 25364450 PMCID: PMC4214465 DOI: 10.3892/ol.2014.2524] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Accepted: 08/01/2014] [Indexed: 02/06/2023] Open
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare soft tissue sarcoma, previously referred to as clear cell sarcoma-like gastrointestinal tumor (CCSLGT) and also commonly reported in the literature as clear cell sarcoma of the gastrointestinal tract (CCS-GI). The current study reports a case of GNET arising in the stomach of a 17-year-old male, who presented with symptoms of fatigue, anemia and low temperature. Examination with positron emission tomography-computed tomography revealed a soft tissue mass in the gastric antrum. Subsequently, radical distal gastric resection was performed, and the mass measured 6.0×4.0×3.5 cm3. Histopathological analysis revealed that the tumor cells were arranged in nests and focally formed fascicular, pseudopapillary, pseudoalveolar and rosette-like growth patterns. Osteoclast-like giant cells were also observed. Immunohistochemically, the tumor cells were positive for S-100 protein, vimentin and BCL-2, and negative for HMB45, Melan-A, CD117, CD34 and CD99. Additionally, the osteoclast-like giant cells were positive for CD68. Fluorescence in situ hybridization demonstrated EWSR1 gene rearrangement. After 10 months of follow-up, no evidence of recurrence or metastasis was observed. As GNET is currently classified differently and under various names in the literature, the information provided by this case study and review is predicted to be useful towards the accurate diagnosis, treatment and prognosis of this rare tumor type.
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Affiliation(s)
- Jie Kong
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | - Nan Li
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | - Shiwu Wu
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | - Xingmei Guo
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | - Congyou Gu
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
| | - Zhenzhong Feng
- Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China
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Yegen G, Güllüoğlu M, Mete Ö, Önder S, Kapran Y. Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract. Int J Surg Pathol 2014; 23:61-7. [DOI: 10.1177/1066896914547046] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Clear cell sarcoma is a rare tumor classically associated with tendons and aponeuroses of lower extremities of young adults and has a distinctive histopathologic and molecular profile. It has been rarely described in other locations other than soft tissues, including the gastrointestinal tract. Herein we report a case of clear cell sarcoma of gastrointestinal tract arising in the ileum, which is rich in osteoclast-like giant cells with a review of the literature.
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Affiliation(s)
| | | | - Özgür Mete
- University of Toronto, Toronto, Ontario, Canada
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15
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Ishii D, Inagaki M, Shonaka T, Akabane H, Yanagida N, Shomura H, Orimo T, Aiyama T, Sato K, Nakano S. Clear cell sarcoma of the esophagus: report of a case. Clin J Gastroenterol 2014; 7:228-32. [PMID: 26183741 DOI: 10.1007/s12328-014-0479-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 03/12/2014] [Indexed: 01/19/2023]
Abstract
We report a rare case of clear cell sarcoma of the esophagus and review the literature regarding clear cell sarcomas of the gastrointestinal tract. A 57-year-old male was admitted with dysphagia during swallowing. Preoperative imaging studies, including upper gastrointestinal endoscopy and endoscopic ultrasonography, showed that the tumor was located between the mucosa and the muscularis propria of the lower esophagus. We performed subtotal esophagectomy with gastric tube reconstruction. Pathological findings of the tumor showed mixed spindle cells and oval cells. Immunohistochemical staining showed that the tumor cells were positive for S-100, vimentin and neuron-specific enolase and negative for α-smooth muscle actin, myoglobin and c-kit. Fluorescence in situ hybridization using a Ewing sarcoma breakpoint region 1 probe showed split signals in a small percentage of cells. We finally diagnosed the patient with clear cell sarcoma of the esophagus.
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Affiliation(s)
- Daisuke Ishii
- Division of Surgery, Hokkaido P.W.F.A.C Asahikawa-Kosei General Hospital, 1 Jo 24 Chome 111, 1 Jodori, Asahikawa, 078-8211, Japan,
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16
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Clear cell sarcoma-like tumor of the gastrointestinal tract, presenting as a second malignancy after childhood hepatoblastoma. Case Rep Med 2014; 2014:984369. [PMID: 24715928 PMCID: PMC3970439 DOI: 10.1155/2014/984369] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2013] [Accepted: 12/29/2013] [Indexed: 12/13/2022] Open
Abstract
Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm arising within the wall of the small bowel, stomach, or large bowel, predominantly in children and young adults. It is an aggressive tumor with a high rate of local recurrence, metastases, and early death from disease. Histologically, it is composed of relatively monomorphic ovoid or round cells with clear to eosinophilic cytoplasm, arranged in sheets and sometimes papillary or alveolar architectures, often with CD68-positive osteoclast-like giant cells in variable numbers, and is associated with EWSR1-CREB1 gene fusions. Its pathogenesis is unknown, and histologically it can be easily confused with a variety of intra-abdominal neoplasms. We describe a case of CCSLGT with molecular characterization, presenting as an acutely obstructing small bowel mass in a 33-year-old male, which occurred as a second malignant neoplasm 20 years after treatment with surgery, radiotherapy, and cisplatin and doxorubicin chemotherapy for childhood hepatoblastoma. This gives further insight into the clinical setting of this highly aggressive neoplasm and highlights the use of radiation therapy as a possible etiologic factor.
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17
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Fisher C. The diversity of soft tissue tumours withEWSR1gene rearrangements: a review. Histopathology 2013; 64:134-50. [DOI: 10.1111/his.12269] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2013] [Accepted: 08/27/2013] [Indexed: 12/14/2022]
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Abstract
EWSR1-CREB1 and EWSR1-ATF1 are gene fusions of which one or both have now been consistently described in 5 histopathologically and behaviorally diverse neoplasms: angiomatoid fibrous histiocytoma, conventional clear cell sarcoma (of tendons and aponeuroses), clear cell sarcoma-like tumor of the gastrointestinal tract, hyalinizing clear cell carcinoma of the salivary gland, and primary pulmonary myxoid sarcoma. Some of the tumors in this group have been described only recently, and others have been the subject of recent genetic insights contributing to their characterization. These neoplasms are all rare; yet, the increasing frequency with which EWSR1-CREB1 and EWSR1-ATF1 fusions are being described in separate entities is noteworthy. The additional molecular mechanisms by which tumors with such variable morphologic, immunohistochemical, and clinical phenotypes are generated are yet to be understood. We review the clinicopathologic and molecular features of this group of neoplasms unified by the presence of EWSR1-CREB1 and EWSR1-ATF1 genetic fusions.
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19
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Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract. Am J Surg Pathol 2012; 36:857-68. [PMID: 22592145 DOI: 10.1097/pas.0b013e31824644ac] [Citation(s) in RCA: 148] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4 patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.
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20
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D'Amico FE, Ruffolo C, Romeo S, Massani M, Dei Tos AP, Bassi N. Clear cell sarcoma of the ileum: report of a case and review of the literature. Int J Surg Pathol 2011; 20:401-6. [PMID: 22207412 DOI: 10.1177/1066896911428073] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Clear cell sarcoma of the gastrointestinal tract (CCS-GI) is an extremely rare and aggressive tumor, which often mimics other neoplastic processes. Because of this feature, its real incidence may have been underestimated, especially in the past when genetic tests were less available than nowadays. To date, less then 30 cases have been described in the literature on the GI tract. CASE PRESENTATION We report the case of a 69-year-old woman who presented with active rectal bleeding. After a negative colonoscopy, the patient underwent a video-capsule endoscopy. The latter detected an ileal mass that was surgically resected. The microscopic appearance was consistent with a malignant mesenchymal neoplasm; immunohistochemistry was positive for S100 protein, CD56, and INI1. Fluorescence in situ hybridization showed a translocation involving the EWSR1 (Ewing sarcoma 1) gene region. All these findings were consistent with a CCS-GI. CONCLUSION Herein we present a case of CCS-GI, discuss its clinical and pathological features, and review the literature on the subject.
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Affiliation(s)
- Francesco E D'Amico
- II Department of Surgery (IV unit), Regional Hospital Ca' Foncello, Treviso, Italy.
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21
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Abstract
Several unusual stomach tumors have been recently described. In addition, some tumors that are often encountered in other sites may rarely occur as primary gastric tumors. The diagnostic surgical pathologist needs to be aware of some of these lesions to prevent misdiagnosis. This overview discusses the key clinical features, pathology, immunohistochemistry, and relevant molecular findings of multiple minute gastrointestinal stromal tumors and interstitial cell of Cajal hyperplasia, nerve sheath tumors (schwannoma and perineurioma), gastroblastoma, granular cell tumor, glomus tumor, plexiform angiomyxoid myofibroblastic tumor, and primary clear cell sarcoma of the gastrointestinal tract that occur as primary gastric neoplasms.
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Affiliation(s)
- Lai Mun Wang
- Oxford University Hospitals Trust, University of Oxford, Oxford, UK
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22
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Shenjere P, Salman WD, Singh M, Mangham DC, Williams A, Eyden BP, Howard N, Knight B, Banerjee SS. Intra-abdominal clear-cell sarcoma: a report of 3 cases, including 1 case with unusual morphological features, and review of the literature. Int J Surg Pathol 2011; 20:378-85. [PMID: 22084426 DOI: 10.1177/1066896911425485] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Clear-cell sarcoma (CCS) is a soft-tissue neoplasm that morphologically resembles cutaneous malignant melanoma but has a distinct molecular profile. Gastrointestinal and intra-abdominal CCSs are very rare. Here, the authors present 3 cases of intra-abdominal CCS and review the literature. Of these cases, 2 involved the small bowel, and 1 involved the peritoneum. Cases 1 and 3 had the characteristic CCS morphology, but case 2 was morphologically unusual and therefore difficult to diagnose. It had relatively small cells with less prominence of clear cells; many pseudoglandular structures were also present. It also showed aberrant expression of epithelial membrane antigen (EMA). The other 2 cases also involved some diagnostic uncertainty and were therefore referred to specialized centers. The authors wish to emphasize the importance of molecular studies in making a conclusive diagnosis of intra-abdominal CCS.
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Affiliation(s)
- Patrick Shenjere
- Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.
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23
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Zhang W, Shen Y, Wan R, Zhu Y. Primary clear cell sarcoma of the sacrum: a case report. Skeletal Radiol 2011; 40:633-9. [PMID: 21181468 DOI: 10.1007/s00256-010-1077-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2010] [Revised: 12/01/2010] [Accepted: 12/02/2010] [Indexed: 02/02/2023]
Abstract
Clear cell sarcoma, first described by Enzinger in 1965, is an uncommon malignant soft tissue neoplasm that displays melanocytic differentiation. It occurs predominantly in the soft tissue of the extremities in young adults or children. Primary clear cell sarcoma of the bone is extremely rare, only seven cases have been reported to our knowledge. We present here a case of a huge primary clear cell sarcoma of the sacrum arising in a 25-year-old man. The average percentage of melanin content in the tumor was 9.25 ± 6.71%, which resulted in hypointense signal in T2-weighted and heterogeneous hyperintense signal in T1-wieghted images of magnetic resonance imaging (MRI). The patient was treated with curettage of the mass and neither further radiotherapy nor chemotherapy had been provided. The patient had local regrowth of tumor at 9 months after surgery. To our knowledge, this is the first case of CCS in the axial skeleton documented in English literature.
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Affiliation(s)
- Weibin Zhang
- Department of Orthopaedics, Rui Jin Hospital, affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Wang WL, Mayordomo E, Zhang W, Hernandez VS, Tuvin D, Garcia L, Lev DC, Lazar AJ, López-Terrada D. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol 2009; 22:1201-9. [PMID: 19561568 DOI: 10.1038/modpathol.2009.85] [Citation(s) in RCA: 161] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Unlike melanoma, clear cell sarcoma harbors either a t(12;22)(q13;q12) recurrent translocation, resulting in an EWSR1/ATF1 chimeric gene, or less commonly a t(2;22)(q34;q12) translocation fusing EWSR1 and CREB1. Few studies have examined the prevalence of all chimeric types and variants to assess the usage of ancillary genetic testing in routine diagnosis. We investigated rearrangement prevalence in 17 clear cell sarcomas, two positive control cell lines, and two melanomas (negative controls). Fluorescence in situ hybridization (FISH) analysis using the LSI EWSR1 break-apart probe and a reverse transcription polymerase chain reaction (RT-PCR) assay optimized for formalin-fixed paraffin-embedded tissue to detect all four reported EWSR1/ATF1 clear cell sarcoma chimeric types and the EWSR1/CREB1 variant was performed. All 15 cases available for testing by FISH were positive for EWSR1 rearrangement including two cases with insufficient RNA for RT-PCR. Thirteen of 15 cases successfully tested by RT-PCR harbored a type 1 chimeric transcript (EWSR1 exon 8/ATF1 exon 4), of which five tumors simultaneously carried a type 2 chimeric transcript (EWSR1 exon 7/ATF1 exon 5). One case carried a type 2 transcript alone and one case contained an EWSR1/CREB1 transcript. Both control cases were positive by both techniques with one case carrying both types 1 and 2 chimeric transcripts and the other types 2 and 3 (EWSR1 exon 10/ATF1 exon 5). Consequently, both techniques are equally effective in assessing for an EWSR1 rearrangement and are useful ancillary diagnostic tests for clear cell sarcoma. They also reinforce the prevalence of this translocation in these tumors. In addition, EWSR1-CREB1 was identified in a clear cell sarcoma of soft tissue providing further evidence that this chimeric variant is not exclusive to gastrointestinal clear cell sarcomas and should be included in RT-PCR assays of soft tissue clear cell sarcomas.
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Affiliation(s)
- Wei-Lien Wang
- Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-2313, USA
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Abstract
Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile. Gastrointestinal CCS is very rare and most reported cases are in adults. We describe a 10-year-old female with a 4-month history of anemia who later developed fever, weight loss and abdominal pain. She was subsequently found to have a large infiltrative gastric mass. A diagnosis of CCS was confirmed by molecular and cytogenetic studies. This case illustrates the necessity of a multimodal approach, particularly the use of molecular studies, in the diagnostic evaluation of rare tumors presenting in unusual sites.
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Affiliation(s)
- Joanne P Lagmay
- Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA.
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26
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Tirabosco R, Lang-Lazdunski L, Diss TC, Amary MFC, Rodriguez-Justo M, Landau D, Lorenzi W, Flanagan AM. Clear cell sarcoma of the mediastinum. Ann Diagn Pathol 2009; 13:197-200. [DOI: 10.1016/j.anndiagpath.2008.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Guler ML, Daniels JA, Abraham SC, Montgomery EA. Expression of melanoma antigens in epithelioid gastrointestinal stromal tumors: a potential diagnostic pitfall. Arch Pathol Lab Med 2008; 132:1302-6. [PMID: 18684030 DOI: 10.5858/2008-132-1302-eomaie] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/10/2008] [Indexed: 11/06/2022]
Abstract
CONTEXT Most gastric gastrointestinal stromal tumors (GISTs) express CD117/c-kit, as do a subset of metastatic melanomas, leading to a diagnostic dilemma in some cases. OBJECTIVE To further differentiate GISTs from melanoma, we investigated expression of melanoma markers in GISTs using a well-characterized set of gastric lesions on tissue microarrays. DESIGN Tissue microarrays from paraffin-embedded tissue cores from 38 patients were stained with S100 protein, HMB-45, and Melan-A antibodies. All cases had been previously stained with CD117/c-kit and CD34 antibodies. All were reactive with CD117/c-kit, and 88.2% expressed CD34. RESULTS S100 protein was focally expressed in 2 (5.3%) of 38 GISTs; these lesions lacked HMB-45 and Melan-A labeling. No tumor labeled with HMB-45, but 4 (10.6%) of 38 cases labeled with Melan-A antibodies. The Melan-A-reactive cases were all S100 negative and CD34 positive. The S100-reactive cases were spindle cell neoplasms, whereas the Melan-A-reactive cases were epithelioid neoplasms (4/9; 44%). An additional 15 standard sections of separate cases of epithelioid GISTs were then labeled with Melan-A, and 5 (33%) of 15 showed at least focal labeling. CONCLUSIONS Melan-A staining can be encountered in a subset of epithelioid GISTs, a finding that can suggest a differential diagnosis of melanoma. In this series, the Melan-A-reactive cases lacked S100 protein and expressed CD34, both of which would be unlikely in melanoma. As such, a panel approach is best in differentiating epithelioid GISTs from melanoma.
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Affiliation(s)
- Mehmet L Guler
- Department of Pathology, Johns Hopkins University, Baltimore, MD 21231, USA
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Gastrointestinal melanoma or clear cell sarcoma? Molecular evaluation of 7 cases previously diagnosed as malignant melanoma. Am J Surg Pathol 2008; 32:858-66. [PMID: 18408594 DOI: 10.1097/pas.0b013e31815b8288] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Clear cell sarcoma (CCS) is a rare tumor classically associated with the tendons and aponeuroses of distal extremities of young adults. CCS and malignant melanoma (MM) share immunohistochemical profiles and ultrastructural features, but classic CCS has characteristic morphology with low mitotic activity and minimal pleomorphism. Occasional cases show pleomorphism, high mitotic index, and/or melanin pigmentation, making CCS indistinguishable from MM based on morphology. However, CCS is genetically distinct owing to its consistent association with a t(12;22)(q13;q12) chromosomal translocation, leading to the formation of the EWS/ATF1 fusion transcript. This translocation has never been documented in cutaneous melanoma, and thus is regarded as specific for CCS. Recent evidence suggests that primary "malignant melanomas" in unusual anatomic sites, most notably the gastrointestinal (GI) tract, may be CCS. This is supported by 11 cases of primary GI CCS with the t(12;22) translocation. We used reverse-transcription polymerase chain reaction and fluorescence in situ hybridization to examine whether a proportion of cases diagnosed as MM of the GI tract in patients without a history of cutaneous MM actually represent primary GI CCS. In total, we examined 7 cases: Four with no prior history of MM, 2 with histories of cutaneous MM, and 1 with an anal MM. All 4 cases for which there was no history of cutaneous/mucosal MM harbored the EWS/ATF1 fusion transcript. We report the largest series of GI CCS and have shown that molecular studies may be warranted in cases that otherwise seem to represent MM of unusual primary locations.
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30
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Abdulkader I, Cameselle-Teijeiro J, de Alava E, Ruiz-Ponte C, Used-Aznar MM, Forteza J. Intestinal clear cell sarcoma with melanocytic differentiation and EWS [corrected] rearrangement: report of a case. Int J Surg Pathol 2008; 16:189-93. [PMID: 18417679 DOI: 10.1177/1066896907306841] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A clear cell sarcoma-like tumor with osteoclast-like giant cells of the gastrointestinal tract without immunoexpression of CD117 was recently proposed as a new tumor entity. In this article, a case of a 37-year-old man with a neoplasm of the jejunum composed of polygonal cells with clear to eosinophilic cytoplasm forming nests and fascicles is reported. Giant cells were not identified. Immunohistochemically, the tumor cells expressed strongly S100 protein, human melanoma black 45, platelet-derived growth factor receptor alpha, B-cell lymphoma 2, p53, and to a lesser extent vimentin, neuron-specific enolase, and epithelial membrane antigen. Mindbomb homolog-1 index was 35%. Immunoreactivity for CD34 and CD117 was negative. The fluorescence in situ hybridization analysis showed a translocation involving chromosome 22q12, the diagnostic hallmark of clear cell sarcoma of soft tissues. This case indicates a close histogenetic relationship with the recently reported clear cell sarcoma with osteoclast-like giant cells of the gastrointestinal tract, as well as with the clear cell sarcoma of soft tissues.
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Affiliation(s)
- Ihab Abdulkader
- Department of Pathology, Hospital Clínico Universitario, SERGAS, University of Santiago de Compostela, Galicia, Spain.
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31
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Marcon N, Montagne K, Corby S, Ayav A, Plénat F, Champigneulle J. Sarcome à cellules claires primitif de l’iléon. Ann Pathol 2007; 27:369-72. [DOI: 10.1016/s0242-6498(07)78276-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Wardelmann E, Büttner R, Merkelbach-Bruse S, Schildhaus HU. Mutation analysis of gastrointestinal stromal tumors: increasing significance for risk assessment and effective targeted therapy. Virchows Arch 2007; 451:743-9. [PMID: 17701051 DOI: 10.1007/s00428-007-0473-9] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2007] [Revised: 07/06/2007] [Accepted: 07/06/2007] [Indexed: 11/26/2022]
Abstract
Molecular characterization of gastrointestinal stromal tumors (GISTs) plays an increasing role not only for the patient's prognosis but also for treatment options and in the context of resistance to therapy. Several mutational subtypes in KIT or platelet-derived growth factor receptor-alpha (PDGFRalpha) have been identified to be correlated with a different clinical behavior of GISTs. In KIT exon 11, deletions in the proximal part are associated with a high metastatic risk, whereas duplications in the distal part lead to a less aggressive phenotype. GISTs of the small bowel with a duplication in KIT exon 9 are often high risk tumors. In contrast, PDGFRalpha exon 18 mutated GISTs tend to have a low malignant potential. The authors suggest to include these molecular data together with classical parameters such as mitotic count and tumor size into the risk assessment of GISTs. The first choice for treatment of GISTs is still the surgical resection. In advanced tumors, which cannot be R0 resected, the neoadjuvant treatment with the tyrosine kinase inhibitor imatinib is now well established. Furthermore, an adjuvant treatment of locally R0-resected intermediate and high risk tumors is evaluated in several international clinical trials. For metastatic disease, treatment with imatinib is still the first option, but with new upcoming substances, the molecular characterization of GISTs may become mandatory. Very recently, it has been shown that sunitinib may be especially effective in GISTs with KIT exon 9 mutation, whereas these tumors show only an intermediate response to imatinib. A European Organisation for Research and Treatment of Cancer clinical trial randomizing patients according to their mutational status is under preparation. Secondary resistance to imatinib treatment is increasing, at least partly due to secondary mutations in the tyrosine kinase domain of the KIT receptor. Once a lesion has been shown to carry such a mutation, the local excision may be useful, mean while still responding metastases are further controlled by continuing imatinib. Taken together, the molecular characterization of GISTs turns out to play a central role before and during the treatment with tyrosine kinase inhibitors, which have improved the treatment of GIST patients dramatically.
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Affiliation(s)
- Eva Wardelmann
- Department of Pathology, University of Bonn Medical School, Sigmund-Freud-Strasse 25, 53127 Bonn, Germany.
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Comin CE, Novelli L, Tornaboni D, Messerini L. Clear cell sarcoma of the ileum: report of a case and review of literature. Virchows Arch 2007; 451:839-45. [PMID: 17636326 DOI: 10.1007/s00428-007-0454-z] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2007] [Accepted: 03/06/2007] [Indexed: 12/23/2022]
Abstract
Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile and with morphological features resembling those of melanoma. CCS has been rarely described in other locations other than the soft tissues, including the gastrointestinal tract. In this study, we report a case of CCS arising in the ileum of a 31-year-old woman. Histologically, the tumor involved the entire thickness of the intestinal wall. Tumor cells were polygonal or fusiform, with clear or eosinophilic cytoplasm, arranged in a uniform nested to fascicular growth pattern. Immunohistochemical studies revealed strong positivity for vimentin and S-100 protein. HMB-45, Melan-A, tyrosinase, cytokeratins, EMA, smooth muscle actin, CD34, CD31, CD117, CD99, synaptophysin, chromogranin A, CD56, and NSE were negative. Fluorescence in situ hybridization analysis demonstrated the presence of a t(12;22)(q13;q12) translocation, the diagnostic hallmark of CCS of soft parts. The present case, together with a detailed review of the literature on this topic, demonstrates that the gastrointestinal tract is a possible site of CCS of soft tissues and that making a reliable diagnosis of this tumor requires cytogenetic or molecular diagnostic investigations.
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Affiliation(s)
- Camilla E Comin
- Dipartimento di Patologia Umana ed Oncologia, Università degli Studi di Firenze, V.le Morgagni, 85, 50134 Firenze, Italy.
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Kirsch R, Gao ZH, Riddell R. Gastrointestinal stromal tumors: diagnostic challenges and practical approach to differential diagnosis. Adv Anat Pathol 2007; 14:261-85. [PMID: 17592256 DOI: 10.1097/pap.0b013e3180ca826a] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Over the last decade, gastrointestinal stromal tumors (GISTs) have evolved from histogenetically obscure gastrointestinal mesenchymal tumors to well-defined tumors with distinctive clinical, morphologic, ultrastructural, histogenetic, and molecular characteristics, for which targeted therapy is available. This is largely attributable to the discovery of CD117 overexpression and activating mutations in c-kit or platelet-derived growth factor alpha genes in most of GISTs. The availability of specific diagnostic tests and targeted therapy for GISTs has led to an increased awareness of these tumors. At the same time, the list of potential GIST mimics has lengthened considerably and it has become increasingly important that GISTs be distinguished from their mimics because correct diagnosis has implications for both treatment and prognosis. The purpose of this review is to provide an update of the expanding differential diagnosis of GISTS, to draw attention to unusual GIST variants, to provide a practical approach the differential diagnosis of GISTs and to highlight some of the challenges faced by pathologists in resolving this differential diagnosis.
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Affiliation(s)
- Richard Kirsch
- Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
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Hallor KH, Micci F, Meis-Kindblom JM, Kindblom LG, Bacchini P, Mandahl N, Mertens F, Panagopoulos I. Fusion genes in angiomatoid fibrous histiocytoma. Cancer Lett 2007; 251:158-63. [DOI: 10.1016/j.canlet.2006.11.014] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2006] [Accepted: 11/13/2006] [Indexed: 12/11/2022]
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Antonescu CR, Nafa K, Segal NH, Dal Cin P, Ladanyi M. EWS-CREB1: a recurrent variant fusion in clear cell sarcoma--association with gastrointestinal location and absence of melanocytic differentiation. Clin Cancer Res 2006; 12:5356-62. [PMID: 17000668 DOI: 10.1158/1078-0432.ccr-05-2811] [Citation(s) in RCA: 219] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE Clear cell sarcoma (CCS) usually arises in the lower extremities of young adults and is typically associated with a t(12;22) translocation resulting in the fusion of EWS (EWSR1) with ATF1, a gene encoding a member of the cyclic AMP-responsive element binding protein (CREB) family of transcription factors. CCS arising in the gastrointestinal tract is rare and its pathologic and molecular features are not well defined. EXPERIMENTAL DESIGN We report a novel variant fusion of EWS to CREB1, a gene at 2q32 encoding another CREB family member highly related to ATF1, detected in three women with gastrointestinal CCS. All three cases contained an identical EWS-CREB1 fusion transcript that was shown by reverse transcription-PCR. In two of the cases tested, EWS gene rearrangement was also confirmed by fluorescence in situ hybridization and the EWS-CREB1 genomic junction fragments were isolated by long-range DNA PCR. RESULTS Morphologically, all three tumors lacked melanin pigmentation. By immunohistochemistry, there was a strong and diffuse S100 protein reactivity, whereas all melanocytic markers were negative. Ultrastructurally, two of the cases lacked melanosomes. The melanocyte-specific transcript of MITF was absent in two cases, and only weakly expressed in the third case. The Affymetrix gene expression data available in one case showed lower expression of the melanocytic genes MITF, TYR, and TYRP1, compared with four EWS-ATF1-positive CCSs of non-gastrointestinal origin. CONCLUSIONS EWS-CREB1 may define a novel subset of CCS that occurs preferentially in the gastrointestinal tract and shows little or no melanocytic differentiation. Thus, evidence of melanocytic lineage or differentiation is not a necessary feature of sarcomas with gene fusions involving CREB family members.
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Affiliation(s)
- Cristina R Antonescu
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, and Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Coindre JM, Hostein I, Terrier P, Bouvier-Labit C, Collin F, Michels JJ, Trassard M, Marques B, Ranchere D, Guillou L. Diagnosis of clear cell sarcoma by real-time reverse transcriptase-polymerase chain reaction analysis of paraffin embedded tissues. Cancer 2006; 107:1055-64. [PMID: 16878328 DOI: 10.1002/cncr.22099] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Clear cell sarcoma (CCS) is a rare tumor with a very poor prognosis that occurs predominantly in the distal extremities of young adults. Most patients bear the t(12;22) reciprocal translocation, which involves the EWS and ATF1 genes. The diagnosis of CCS usually is easy but may be challenging in unusual sites, and the detection of EWS-ATF1 fusion transcripts is helpful to rule out a metastatic melanoma. METHODS Forty-four patients with CCS and 14 conventional melanomas were examined for the presence of EWS-ATF1 transcripts by using real-time polymerase chain reaction (PCR) analysis on paraffin embedded tissues, including frozen samples for 9 CCS samples and 9 melanoma samples. Prior to molecular analysis, the diagnosis of CCS was considered certain in 35 patients and as probable in 9 patients on the basis of location, histologic features, and immunohistochemical profile. Treatment modalities and follow-up were available for 41 patients with CCS. RESULTS EWS-ATF1 fusion transcripts were detected in 38 paraffin embedded CCS tissues (86% of all samples; 93% of interpretable samples), 3 samples (7%) were negative, and 3 samples (7%) were considered uninterpretable. Fusion transcripts were detected in 7 of 9 samples for which the diagnosis of CCS was considered probable. EWS-ATF1 transcripts were not detected in the 14 samples of melanoma. Results from frozen tissues were concordant with those from all corresponding paraffin embedded samples. Twenty-eight of 41 patients (68%) experienced lymph node and/or distant metastasis, and the 5 year-survival rate was 44%. Mitotic index and histologic grade were predictive of survival and distant metastasis. CONCLUSIONS The results of this study showed that the molecular detection of EWS-ATF1 fusion transcript by real-time PCR on paraffin embedded tissues is a sensitive and specific method for the diagnosis of CCS. It is an efficient tool for the diagnosis of unusual tumors, especially with regard to its distinction from melanoma. The current results also confirmed the poor prognosis for patients with this tumor type. Mitotic index and grade were predictive factors for survival and distant metastasis.
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