Primary Pleuropulmonary Synovial Sarcoma

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Nov 6, 2018 - Salem, North Carolina 27103. Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.
Case Reports

Primary Pleuropulmonary Synovial Sarcoma Diagnosed by Fine Needle Aspiration with Cytogenetic Confirmation

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A Case Report

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Cullen A. Taylor, M.D., Amanda Barnhart, M.A., Mark J. Pettenati, Ph.D., and Kim R. Geisinger, M.D.

Background

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of recurrent hemopneumothorax. Previous surgical pathology on decorticated pleura was interpreted as a reactive Pleuropulmonary synovial sarcomas (PPSSs) are rare neomesothelial proliferation at another institution. Upon replasms that have been well described in recent years, alferral, CT-guided transthoracic FNA was performed. though there are only very infrequent reports within the cySmears revealed a highly cellular, dispersed “small round tology literature. Such lesions present a diagnostic challenge blue cell” neoplasm in a hemorrhagic background. The cyon fine needle aspiration (FNA) due to several factors, partomorphology, in conjunction ticularly when the aspirate with a select immunoperoximaterial displays monophasic, Conventional and molecular dase panel, was diagnostic of small cell or poorly differentiated morphology. Immunocytogenetics subsequently provided PPSS. Conventional and molecular cytogenetics subseperoxidase studies on cell block definitive confirmation of the quently provided confirmation material and confirmation of the diagnosis. with molecular cytogenetics diagnosis. are important tools to establish Conclusion the diagnosis and determine PPSSs are uncommon neoplasms seldom diagnosed by appropriate therapy. We report a case of PPSS in a 27FNA, with only very rare reports in the cytology literature. year-old man diagnosed by computed tomography (CT)– Although their cytomorphology has been well described, guided FNA with confirmation by conventional and molecmonophasic tumors and other morphologic variants present ular cytogenetics. a diagnostic challenge and may be difficult to discern from a Case variety of neoplastic and reactive/reparative processes. Emphasis should be placed upon securing material at the time A 27-year-old man presented with several rapidly enlargof aspiration for immunoperoxidase studies (cell block or ing, pleura-based masses following a several-month history

From the Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, U.S.A. Dr. Taylor was Fellow in Cytopathology, Wake Forest University Medical Center and North Carolina Baptist Hospital, and currently is Pathologist, Forsyth Medical Center, Winston-Salem, North Carolina. Ms. Barnhart was Medical Student and currently is House Officer in Pathology. Dr. Pettenati is Professor, Department of Pediatrics (Medical Genetics). Dr. Geisinger is Professor and Director of Surgical Pathology and Cytology, Department of Pathology. Address correspondence to: Cullen A. Taylor, M.D., Department of Pathology, Forsyth Medical Center, 3333 Silas Creek Parkway, WinstonSalem, North Carolina 27103. Financial Disclosure: The authors have no connection to any companies or products mentioned in this article. Received for publication May 4, 2004. Accepted for publication October 4, 2004.

0001-5547/05/4906-0673/$19.00/0 © The International Academy of Cytology

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core biopsy). In equivocal cases, conventional and/or molecular cytogenetic studies may be needed. (Acta Cytol 2005;49:673–676) Keywords: sarcoma, synovial; aspiration biopsy, fineneedle; pleural neoplasms; lung cancer.

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A 27-year-old man initially presented to a large referral community hospital with symptoms related to recurrent left hemopneumothorax requiring thoracotomy and decortication of blebs involving the left lower lobe. At surgery, the left lung was coated with a thick, fibrinous exudate with abundant blood loculated in the left hemithorax. No tumor was identified grossly. Histopathology of pleural stripping revealed a proliferation of bland spindle cells in association with a thickened, fibrotic pleura (Figure 1). An extended immunophenotypic panel revealed the cell population to stain convincingly with vimentin and CAM5.2. There was no staining with antibodies directed against the following antigens: CEA, B72.3, CD15, CD34, CD45, chromogranin and synaptophysin. The findings were interpreted as most consistent with a reactive mesothelial proliferation secondary to the recurrent hemopneumothorax, with the directive that further sampling would be necessary if a neoplasm was clinically suspected. The patient was subsequently placed on antibiotics and followed over the ensuing months with serial chest radiographs. Nine months later he presented with worsening shortness of breath, hemoptysis and several large pleura-based masses on CT. The patient was referred to our institution for further diagnostic and management. CT revealed 2 pleura-based index lesions measuring > 13 and 10 cm in largest dimensions. The masses extended to encase the left hemithorax and surround the left bronchovascular structures. The clinical impression was Askin

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leuropulmonary synovial sarcomas (PPSSs) are rare neoplasms that have been well described in recent years,1-6 although there are only very infrequent reports within the cytology literature.7 Such lesions present a diagnostic challenge on fine needle aspiration (FNA) due to several factors, particularly when the aspirate material displays monophasic, small cell or poorly differentiated morphology.7-13 Immunoperoxidase studies on cell block material and confirmation with molecular cytogenetics are important tools to establish the diagnosis and determine appropriate therapy.14-18 We report a case of PPSS in a 27year-old man diagnosed by computed tomography (CT)–guided FNA with confirmation by conventional and molecular cytogenetics.

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tumor (primitive neuroectodermal tumor [PNET] of the chest wall). CT-guided, transthoracic, 21-gauge FNA was performed on the peripheral area of tumor involving the left hemithorax. On-site air-dried smears stained with a modified Wright stain (Diff-Quik method) and paired, alcohol-fixed smears were made from multiple passes. A preliminary interpretation of “small round blue cell neoplasm” was rendered on site, with the recommendation that additional material be obtained for immunoperoxidase studies and cytogenetics. Both air-dried (Diff-Quik method) and alcoholfixed (Papanicolaou method) smears demonstrated a highly cellular aspirate composed of a monomorphous, round to elliptical cell population with bland cytology in a hemorrhagic background (Figure 2). Tumor cells were arranged in loosely cohesive, 2dimensional, patternless sheets with focal areas of cell streaming and clustering around prominent capillaries (Figure 3). Numerous small groups, couplets and single cells were present; rosettes were absent. Individual nuclei displayed hyperchromasia with granular chromatin and occasional small but distinct nucleoli. The nuclear/cytoplasmic ratio was high, with individual cells bearing only a modest amount of delicate, “wispy,” pale blue-grey cytoplasm without vacuolization. No “rhabdoid” or globular cytoplasmic inclusions were observed. The background was replete with stripped nuclei and cytoplasmic remnants of fractured cells. There was no appreciable nuclear molding, crush artifact or Azzopardi phenomenon. Scattered mitoses were seen, as were rare apoptotic cells; geographic necrosis was absent. The cytomorphology was interpreted as probable PPSS, monophasic type; a panel of immunoperoxidase studies was performed to solidify the diagnosis.

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Figure 1 Proliferation of bland spindle cells in association with thickened, fibrotic pleura (hematoxylin-eosin, × 400).

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nally noted at the referring institution and interpreted as mesothelial. Discussion

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Primary lung and pleural sarcomas as a group are uncommon and greatly outnumbered by clinical and morphologic mimics, such as nonneoplastic mesenchymal proliferations, sarcomatoid carcinomas, mesothelial proliferations and metastatic sarcomas.1 SSs most commonly involve the periarticular soft tissue of the extremities but have been observed at diverse sites throughout the body. Within the thorax, PPSS may involve multiple structures or be localized to the chest wall, pleura or lung.1 PPSS is far less common than intrathoracic metastases from its soft tissue counterpart. However, discernment of primary versus metastatic SS is often readily obtained based on clinical and radiologic data; cytomorphology, immunohistochemistry and molecular cytogenetics are presently not helpful with this distinction.1-5,18 Within this setting, PPSS presents a diagnostic challenge on FNA. The diagnosis of PPSS may be established on morphology alone when the aspirate is of excellent quality and classic biphasic elements are seen; however, most cases will require confirmation by another method.7,15,18 Several morphologic subtypes of SS may be particularly problematic, including monophasic fibrous, small cell and poorly differentiated types. Additionally, problems in interpretation may arise in cases when the volume of tumor is low, whether due to poor sampling or to the biologic nature of a particular lesion. When our patient initially presented, there was no tumor identified on imaging or in the operative field and only a small volume on microscopy of the pleural stripping. Argani et al reported a similar case of occult PPSS occurring in a

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Immunoperoxidase studies were performed using standard antigen retrieval techniques on fibrin-clotted cell block material with appropriate controls. Tumor cells demonstrated strong and diffuse positivity when antibodies were directed against CD99 (O13) and bcl2. Scattered tumor cells showed convincing positivity for cytokeratin (AE1/AE3 and CK7) and nerve growth factor receptor (P75). Desmin, muscle-specific actin, neuron-specific enolase and epithelial membrane antigen (EMA) were negative. The cytomorphology combined with the immunophenotype provided ample evidence to establish a diagnosis of PPSS. Subsequently, cytogenetic analysis utilizing GTG-banded metaphases of the aspirate material revealed the presence of a single abnormal clonal cell line with multiple chromosomal abnormalities. Most significant was the presence of t(X;18) (p11.2;q11.2). This translocation has been associated with the diagnosis of synovial sarcoma (SS) independent of the site of origin.18,19 In an effort to exclude Askin tumor, molecular cytogenetic analysis (fluorescence in situ hybridization) with a DNA probe specific to the EWSR1 gene region of 22q12 revealed that the intact gene was present on both copies of chromosome 22, with no evidence of EWSR1 gene splitting. The patient was referred to the oncology department and began 8 cycles of neoadjuvant chemotherapy on an Ewing sarcoma (ES)–type regimen (ifosfamide/ VP-16 alternating with vincristine, dactinomycin and cyclophosphamide). Having survived 7 months following the diagnosis, the patient recently underwent left lobectomy, debridement and intraoperative chemotherapy; the residual tumor demonstrated > 90% necrosis. The morphology of the viable tumor resembled the bland spindle cell proliferation origi-

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Figure 2 Cellular aspirate composed of a monomorphous cell population in a hemorrhagic background (Papanicolaou stain, × 600).

Figure 3 Neoplastic cells clustering around prominent capillaries (Papanicolaou stain, × 600).

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tion t (X;18). Am J Clin Pathol 1996;105:195–199 5. Gaertner E, Zeren HE, Fleming MV, Colby TV, Travis WD: Biphasic synovial sarcoma arising in the pleural cavity: A clinicopathologic study of five cases. Am J Surg Pathol 1996;20:36– 45 6. Nicholson AG, Goldstraw P, Fisher C: Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: A clinicopathological and immunohistochemical review of three cases. Histopathology 1998;33:508–513

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7. Hummel P, Yang GC, Kumar A, Cohen JM, Winkler B, Melamed J, Scholes JV, Jagirdar J: PNET-like features of synovial sarcoma of the lung: A pitfall in the cytologic diagnosis of soft-tissue tumors. Diagn Cytopathol 2001;24:283–288 8. Folpe AL, Schmidt RA, Chapman D, Gown AM: Poorly differentiated synovial sarcoma. Am J Surg Pathol 1998;22:673–682

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9. Van de Rijn M, Barr FG, Xiong QB, Hedges M, Shipley J, Fisher C: Poorly differentiated synovial sarcoma. Am J Surg Pathol 1999;23:106–112

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10. Kilpatrick SE, Teot LA, Stanley MW, Ward WG, Savage PD, Geisinger KR: Fine-needle aspiration biopsy of synovial sarcoma. Am J Clin Pathol 1996;106:769–775 11. Ewing CA, Zakowski MF, Lin O: Monophasic synovial sarcoma: A cytologic spectrum. Diagn Cytopathol 2004;30:19–23

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13. Costa I, Lerma E, Esteve E, Chivite A, von Schilling B, Prat J: Aspiration cytology of lung metastasis of monophasic synovial sarcoma: Report of a case. Acta Cytol (suppl 4) 1997;41:1289– 1292

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2. Zeren H, Moran CA, Suster S, Fishback NF, Koss MN: Primary pulmonary sarcoma with features of monophasic synovial sarcoma. Hum Pathol 1995;26:474–480 3. Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA: Translocation (X;18) in primary synovial sarcoma of the lung. Cancer Genet Cytogenet 1996;88:49–52 4. Kaplan MA, Goodman DM, Satish D, Bhagavan BS, Travis WD: Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome transloca-

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15. Akerman M, Ryd W, Skytting B: Fine-needle aspiration of synovial sarcoma: Criteria for diagnosis: Retrospective reexamination of 37 cases, including ancillary diagnostics: A Scandinavian Sarcoma Group study. Diagn Cytopathol 2003;28:232–238

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1. Essary LR, Vargas SO, Fletcher CD: Primary pleuropulmonary synovial sarcoma: Reappraisal of a recently described anatomic subset. Cancer 2002;94:459–469

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14. Abenoza P, Manivel JC, Swanson PE, Wick MR: Synovial sarcoma: Ultrastructural study and immunohistochemical analysis by a combined peroxidase-antiperoxidase/avidin-biotin-peroxidase complex procedure. Hum Pathol 1986;17:1107–1115

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12. Silverman JF, Landreneau RJ, Sturgis CD, Raab SS, Fox KR, Jasnosz KM, Dabbs DJ: Small-cell variant of synovial sarcoma: Fine-needle aspiration with ancillary features and potential diagnostic pitfalls. Diagn Cytopathol 2000;23:118–123

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young man with unexplained recurrent pneumothorax. They were able to establish the diagnosis after demonstrating the characteristic SYT/SSX gene fusion by reverse transcriptase polymerase chain reaction performed on paraffin-embedded tissue.19 In the present case, based upon clinical data and tumor cytomorphology, our chief differential was PPSS versus ES/PNET. It has been reported that PPSS may have cytologic features that overlap those of ES/PNET.7 Immunohistochemical techniques are typically employed to help resolve the diagnosis in such cases. However, an adequate immunoperoxidase panel may involve a handful of antibodies that may be difficult to obtain/interpret if the amount of tumor material is scant. It is recognized that cytokeratin and EMA positivity are valuable in discerning SS from ES/ PNET. However, the expression of such epitheliumassociated antigens is often quite focal in SS (particularly the monophasic type), and there is considerable risk of false negative interpretation when the studies are performed on a small amount of material.20 ES/PNET may be focally positive for cytokeratin in a minority of instances. Subsequently, there is a risk that tumor expression of CD99 may then erroneously result in a diagnosis of ES/PNET. We found it helpful to apply > 1 epithelium-associated marker to the lesion. Although EMA was negative, AE1/AE3 and CK7 were convincingly positive on the aspirate, and Cam5.2 positivity was demonstrated on the previous outside surgical pathology material. In particularly difficult cases, ultrastructural studies may prove helpful.14,15,17 The subtle elliptical/spindled nature of the tumor cells (better appreciated on Papanicolaou-stained material) in the present case enabled us to favor PPSS over ES/PNET. Therefore, the immunoperoxidase studies were selected and interpreted accordingly. Conventional and molecular cytogenetics subsequently provided definitive confirmation of the diagnosis.

16. Turc-Carel C, Dal Cin P, Liman J, Li F, Sandberg AA: Translocation X;18 in synovial sarcomas. Cancer Genet Cytogenet 1986;23:93–100 17. Åkerman M, Willén H, Carlén B, Mandahl N, Mertens F: Fine needle aspiration (FNA) of synovial sarcoma: A comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA ploidy analysis. Cytopathology 1996;7:187–200 18. Coindre JM, Pelmus M, Hostein I, Lussan C, Bui BN, Guillou L: Should molecular testing be required for diagnosing synovial sarcoma? A prospective study of 204 cases. Cancer 2003;98: 2700–2707 19. Argani P, Askin FB, Colombani P, Perlman EJ: Occult pulmonary synovial sarcoma confirmed by molecular techniques. Pediatr Dev Pathol 2000;3:87–90 20. Corson JM, Weiss LM, Banks-Schlegel SP, Pinkus GS: Keratin proteins and carcinoembryonic antigen in synovial sarcomas: An immunohistochemical study of 24 cases. Hum Pathol 1984; 15:615–621

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