EDUCATIONAL FORUM
Fine-Needle-Aspiration Cytology of a Proximal Type Epithelioid Sarcoma A Case Report Avani A. Pendse, M.B.B.S.,
Ph.D,
and Leslie G. Dodd, M.D*
Epithelioid sarcoma is a rare mesenchymal neoplasm, with an as yet unidentified cell of origin. Two subtypes of epithelioid sarcoma, distal/classic and proximal/large cell type, are recognized in the literature; with the proximal-type having a lower incidence amongst the two. Here, we present a case of proximal-type epithelioid sarcoma in a previously healthy young man. Fine-needleaspiration of a large axillary mass was performed for diagnosis. The cytologic findings included a dispersed population of large epithelioid to polyhedral cells with abundant cytoplasm. Immunohistochemical staining showed coexpression of keratin and vimentin, as well as loss of INI1 staining, consistent with an epithelioid sarcoma, proximal subtype. Diagn. Cytopathol. C 2015 Wiley Periodicals, Inc. 2015;43:859–862. V Key Words: proximal epithelioid sarcoma; epithelioid sarcoma; fine-needle aspiration; INI1
Introduction Epithelioid sarcoma (ES) is a malignant soft tissue neoplasm that is characterized by a distinctive epithelioid phenotype. It is a very rare neoplasm, and is estimated to account for less than 1.0% of all sarcomas.1 ES was initially described in 1970 by Enzinger who published a comprehensive description of the clinical presentation and histologic features of 62 cases of epithelioid sarcoma.2 In his original description he noted that ES can be confused
Resident in Anatomic and Clinical Pathology, Department of Pathology, University of North Carolina, Chapel Hill, North Carolina *Correspondence to: Leslie G. Dodd, MD, Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7525, USA. E-mail: [email protected] Received 21 November 2014; Revised 18 February 2015; Accepted 30 March 2015 DOI: 10.1002/dc.23294 Published online 3 July 2015 in Wiley Online Library (wileyonlinelibrary.com). C 2015 WILEY PERIODICALS, INC. V
with a variety of processes, both benign and malignant, including chronic inflammatory process, necrotizing granulomas and various carcinomas. Currently ES is divided into two distinctive subtypes based on characteristic clinical and morphologic presentations. The conventional or “classic” form tends to occur initially in the subcutaneous soft tissues of the distal extremity.3–5 Histologically, the classic or distal subtype of ES is often characterized by a subcutaneous collection of epithelioid to spindled cells with large foci of central necrosis. The “proximal” subtype of ES is less common and tends to present in the trance, inguinal, genital soft tissues.6,7 The proximal subtype of ES tends to arise in the deep soft tissues and is usually characterized by large, “carcinoma-like” cells that are frequently mistaken for either melanoma or a malignant epithelial process. To date there have been a number of cytologic descriptions of the “classic” or distal variant of ES8–13 but relatively few reports of the proximal subtype of ES.14–16 In the following, we describe the radiographic, histologic, and cytologic features of one of these rare cases and compare our findings to those previously published. In addition, we illustrate the usefulness of a newer immunohistochemical marker (SMARCB1/INI1) as an adjunct to diagnosis of this rare tumor.
Case Report A 20-year-old male with no significant past medical history presented to his physician with a complaint of pain and numbness in his right arm. The duration of symptoms was 3 months. Also during this interval he noted a decrease in strength in his arm. On clinical exam he was noted to have an enlarged and firm axillary mass. Imaging was performed as part of his initial diagnostic workup. Nuclear magnetic resonance imaging of the chest revealed a large multilobulated mass involving the right Diagnostic Cytopathology, Vol. 43, No 10
859
Diagnostic Cytopathology DOI 10.1002/dc
PENDSE AND DODD
Fig. 1. Magnetic resonance imaging of proximal epithelioid sarcoma involving the soft tissue and lymph nodes in the axillary region.
supraclavicular, subpectoral, and axillary regions (Fig. 1). Also noted were multiple enlarged lymph nodes in the axillary region. Additional imaging revealed multiple pulmonary nodules, presumed to be metastatic disease. For initial diagnosis a fine-needle-aspiration (FNA) of one of the axillary nodes was performed. This was ultimately followed by an excisional biopsy of an axillary lymph node at an outside hospital. He was referred to our institution for treatment and began therapy; however, he was noncompliant and was lost to follow-up.
Cytologic Findings Ethanol fixed, Papanicolaou stained and air-dried Diff-Quik stained smears, along with a hematoxylin and eosin (H&E) stained cell block, were prepared from samples obtained from the right axillary mass by FNA. FNA smears were highly cellular with loosely cohesive clusters and dispersed large polygonal cells (Fig. 2). The cells had a plasmacytoid appearance, with an eccentric nucleus and moderate amount of cytoplasm. The nuclei were predominantly vesicular with one or more prominent nucleoli, and rare mitoses were seen. A cell block preparation prepared from aspirated material demonstrated polygonal cells in the background of lymph node and blood. Immunohistochemical (IHC) stains were performed and staining was positive for vimentin, CK8/18, cytokeratin AE1/3, and CD34. On the basis of the cytologic appearance and the IHC results, the lesion was diagnosed as “malignant epithelioid neoplasm, high grade.”
Fig. 2. (A) Diff-Quik stained smears of the fine-needle-aspirate from the right axillary lymph node shows the loosely cohesive and scattered cells in the background of lymphoid tissue and blood. A mitotic figure is present in the center of the filed. (B) On fixed, and Pap stained prep the epithelioid cells are enlarged with irregular nuclear outlines and prominent nucleoli. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
involvement of the lymph node, in an infiltrative pattern, by a metastatic neoplasm composed of epithelioid cells (Fig. 3). The tumor had a nodular growth pattern with small areas of necrosis. The cellular morphology was similar to that observed in the FNA sample. IHC stains performed on the excision specimen were again positive for vimentin, epithelial membrane antigen (EMA), and CD34 (membranous pattern). Additionally, INI1 staining was performed and demonstrated a loss of nuclear localization of the protein in the neoplastic cells (Fig. 4). On the basis of the morphologic appearance and IHC staining, a diagnosis of “Proximal-type epithelioid sarcoma” was rendered.
Histologic Findings
Discussion
A hematoxylin and eosin stained surgical biopsy specimen from the same site (right axilla lymph node) showed
Epithelioid sarcoma (ES) is a high grade, malignant neoplasm that presents in two distinct forms: a “classic”
860
Diagnostic Cytopathology, Vol. 43, No 10
Diagnostic Cytopathology DOI 10.1002/dc
PROXIMAL EPITHELIOID SARCOMA
Fig. 3. H&E stained sections of the right axillary node. Proximal epithelioid sarcoma, characterized by large cells with hyperchromatic nuclei with prominent nucleoli, has metastasized to the lymph node. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 4. INI1 shows a reverse staining pattern where the neoplastic cells show a loss of nuclear INI1 protein expression and normal cells are characterized by an “intact” nuclear staining pattern. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary. com.]
type, usually involving the superficial soft tissues of the distal extremities, and a “proximal” form, most often located in the pelvis, perineum, and genital tract. The classic form has a predilection for the flexor surfaces of the hand, fingers, and forearm. Classical ES often presents as a subcutaneous nodule or plaque like mass that is slow growing and painless. ES is an aggressive malignancy with clinical course often marked by multiple soft tissue recurrences, more proximal to the original lesion, and eventual metastases to the lung, brain, and bone. Interestingly, ES is one of the few sarcomas that tend to metastasize to regional lymph nodes. Treatment of ES is largely surgical and long term prognosis is still relatively poor. The proximal variant of ES shares many of the histologic, molecular, and cytogenetic features of the “classic” type but has a distinctly different clinical presentation. In the proximal subtype, the deeper soft tissues are affected and tumors form more of a solid mass. In addition, the proximal subtype is less common than the classic form (representing about one third of all ES).1 The median age of the proximal type patient is also somewhat older than the classical subtype (40 years vs.30 years). Unfortunately, the proximal subtype is associated with an even more aggressive course than the classic type of ES. Both proximal and classic forms of ES have a peculiar molecular abnormality than can be exploited for diagnostic purposes. ES typically shows multiple gains and losses of various chromosomes, as well as an abnormality at the hSNF5/SMARCB1/INI1 gene locus on chromosome 22.17 This results in an inactivation of the tumor suppressor gene. Inactivation correlates with loss of INI1 protein
expression by IHC and lack of expression of the marker can be used in the diagnosis of ES.18–20 ES is one of a number of neoplasms that demonstrate loss of INI-1 nuclear staining. Other tumors that typically show loss of nuclear INI-1 staining include rhabdoid tumor, myoepithelial tumors, and rare variants of renal carcinomas.20–26 Rhabdoid tumors, arising in either the central nervous system or in the soft tissues, are tumors of infancy, and not likely to be confused with ES.24 Myoepithelial tumors can show some clinical and histologic overlap with ES, but can be distinguished from the later by characteristic histology including the presence of extracellular matrix material. In addition, myoepithelial tumors will stain positive for S100 protein and frequently show EWSR1 gene rearrangement.25 Renal medullary carcinomas will also show loss of INI1 staining but these are lesions that arise in the kidney, and occur almost exclusively in individuals with sickle cell trait.26 Additionally, several entities need consideration while establishing a cytomorphologic and histologic differential diagnosis, including (metastatic) carcinoma, malignant melanoma, plasma cell myeloma, and other epithelioid sarcomas such as epithelioid angiosarcoma and epithelioid malignant peripheral nerve sheath tumors. A careful evaluation of the clinical and radiologic features along with a panel of appropriate immunostains will help arrive at an accurate diagnosis in the majority of cases. To date, the cytologic features of ES are only beginning to be well characterized and illustrated. The single largest series of the FNA findings of ES was published by Lemos et al. in 2008.9 In this study the authors described the features of ten cases of ES (seven primary, Diagnostic Cytopathology, Vol. 43, No 10
861
Diagnostic Cytopathology DOI 10.1002/dc
PENDSE AND DODD
three recurrent). Their findings included: single large cells with intact cytoplasm and enlarged nuclei with prominent nucleoli. They also described some cases showing an “eosinophilic” background material. A second series of nine cases by Cardillo et al.11 noted similar features. This series included two cases of tumors in the buttock region, probably representing the proximal variant of ES. These authors also commented on the presence of interspersed spindled cells and “granuloma-like arrangements” of cells, features not identified in all cases. Our case shows similarity to those previously reported including: a dispersed population of large round cells with irregular nuclear outlines and abundant cytoplasm.14–16 We did not note, however, the “rhabdoid” type of morphology described in the case reported by Gonzalez-Peramato et al.15 As PES represents an extremely rare lesion, it is important to recognize its characteristic cytologic features and how immunohistochemical staining for INI1 can be useful in facilitating a correct diagnosis.
References 1. Oda Y, Dal Cin P, Laskin WB. Epithelioid sarcoma In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumors of soft tissue and bone. Lyon, France: IARC Press; 2013. p 216–218. 2. Enzinger FM. Epithelioid sarcoma: a sarcoma simulating a granuloma or a carcinoma. Cancer 1970;26:1029–1041. 3. Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: A clinicopathologic and immunohistochemical analysis of 106 cases from the french sarcoma group. Am J Clin Pathol 2009;131:222–227. 4. Rekhi B, Gorad BD, Chinoy RF. Clinicopathological features with outcomes of a series of conventional and proximal-type epithelioid sarcomas, diagnosed over a period of 10 years at a tertiary cancer hospital in india. Virchows Arch 2008;453:141–153. 5. Miettinen M, Fanburg-Smith JC, Virolainen M, Schmookler BM , Fetsch JF. Epithelioid sarcoma: An immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol 1999;30:934–942. 6. Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. “Proximaltype” epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol 1997;21:130–146. 7. Hasegawa T, Matsuno Y, Shimoda T, Umeda T, Yokoyama R, Hirohashi S. Proximal-type epithelioid sarcoma: A clinicopathologic study of 20 cases. Mod Pathol 2001;14:655–663.
10. Kitagawa Y, Ito H, Sawaizumi T, et al. Fine needle aspiration cytology of primary epithelioid sarcoma. A report of 2 cases. Acta Cytol 2004;48:391–396. 11. Cardillo M, Zakowski MF, Lin O. Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases. Cancer 2001;93: 246–251. 12. Jogai S, Gupta SK, Goel A, Ahluwalia J, Joshi K. Epithelioid sarcoma. Report of a case with fine needle aspiration diagnosis. Acta Cytol 2001;45:271–273. 13. Zeppa P, Errico ME, Palombini L. Epithelioid sarcoma: Report of two cases diagnosed by fine-needle aspiration biopsy with immunocytochemical correlation. Diagn Cytopathol 1999;21:405–408. 14. Ikeda K, Tate G, Suzuki T, Mitsuya T. Fine needle aspiration cytology of primary proximal-type epithelioid sarcoma of the perineum: A case report. Acta Cytol 2005;49:314–318. 15. Gonzalez-Peramato P, Jimenez-Heffernan JA, Cuevas J. Fine-needle aspiration cytology of “proximal-type” epithelioid sarcoma. Diagn Cytopathol 2001;25:122–125. 16. Bajaj P, Aiyer H, Sinha BK, Jain M, Ashok S. Pitfalls in the diagnosis of epithelioid sarcoma presenting in an unusual site: A case report. Diagn Cytopathol 2001;24:36–38. 17. Modena P, Lualdi E, Facchinetti F, et al.. Smarcb1/ini1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 2005;15:4012–4019. 18. Kohashi K, Izumi T, Oda Y, et al. Infrequent smarcb1/ini1 gene alteration in epithelioid sarcoma: A useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Hum Pathol 2009;40:349–355. 19. Hornick JL, Dal Cin P, Fletcher CD. Loss of ini1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 2009;33:542–550. 20. Le Loarer F, Zhang L, Fletcher CD, et al. Consistent smarcb1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer 2014;53:475–486. 21. Hollman TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 2011;35:e47–e63. 22. Agaimy A. the expanding family of smarcb1(INI1)-deficient neoplasia: Implications of phenotypic, biological, and molecular heterogeneity. Adv Anat Pathol 2014;21:394–410. 23. Siagauke E, Rakheja D, Maddox CL, et al. Absence of expression of smarcb1/ini1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: An immunohistochemical study with implications for diagnosis. Mod Pathol 2006; 19:717–725. 24. Kodet R, Newton WA Jr, Sachs N. Rhabdoid tumors of soft tissue: A clinicopathologic study of 26 cases enrolled on the intergroup rhabdomyosarcoma study. Hum Pathol 1991;22:674–684.
8. Barward A, Dey P, Das A. Fine-needle-aspiration cytology of epithelioid sarcoma. Diagn Cytopathol 2011;39:517–520.
25. Rekhi B, Sable M, Jambheker NA. Histopathological, immunohistochemical and molecular spectrum of myoepithelial tumours of soft tissues. Virchows Arch 2012;461:687–697.
9. Lemos MM, Chaves P, Mendonca ME. Is preoperative cytologic diagnosis of epithelioid sarcoma possible? Diagn Cytopathol 2008; 36:780–786.
26. Calderaro J, Moroch J, Pierron G, et al. SMARCB1/ini1 inactivation in renal medullary carcinoma. Histopathology 2012;61: 428–435.
862
Diagnostic Cytopathology, Vol. 43, No 10
Fine-Needle-Aspiration Cytology of a Proximal Type Epithelioid Sarcoma A Case Report Avani A. Pendse, M.B.B.S.,
Ph.D,
and Leslie G. Dodd, M.D*
Epithelioid sarcoma is a rare mesenchymal neoplasm, with an as yet unidentified cell of origin. Two subtypes of epithelioid sarcoma, distal/classic and proximal/large cell type, are recognized in the literature; with the proximal-type having a lower incidence amongst the two. Here, we present a case of proximal-type epithelioid sarcoma in a previously healthy young man. Fine-needleaspiration of a large axillary mass was performed for diagnosis. The cytologic findings included a dispersed population of large epithelioid to polyhedral cells with abundant cytoplasm. Immunohistochemical staining showed coexpression of keratin and vimentin, as well as loss of INI1 staining, consistent with an epithelioid sarcoma, proximal subtype. Diagn. Cytopathol. C 2015 Wiley Periodicals, Inc. 2015;43:859–862. V Key Words: proximal epithelioid sarcoma; epithelioid sarcoma; fine-needle aspiration; INI1
Introduction Epithelioid sarcoma (ES) is a malignant soft tissue neoplasm that is characterized by a distinctive epithelioid phenotype. It is a very rare neoplasm, and is estimated to account for less than 1.0% of all sarcomas.1 ES was initially described in 1970 by Enzinger who published a comprehensive description of the clinical presentation and histologic features of 62 cases of epithelioid sarcoma.2 In his original description he noted that ES can be confused
Resident in Anatomic and Clinical Pathology, Department of Pathology, University of North Carolina, Chapel Hill, North Carolina *Correspondence to: Leslie G. Dodd, MD, Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7525, USA. E-mail: [email protected] Received 21 November 2014; Revised 18 February 2015; Accepted 30 March 2015 DOI: 10.1002/dc.23294 Published online 3 July 2015 in Wiley Online Library (wileyonlinelibrary.com). C 2015 WILEY PERIODICALS, INC. V
with a variety of processes, both benign and malignant, including chronic inflammatory process, necrotizing granulomas and various carcinomas. Currently ES is divided into two distinctive subtypes based on characteristic clinical and morphologic presentations. The conventional or “classic” form tends to occur initially in the subcutaneous soft tissues of the distal extremity.3–5 Histologically, the classic or distal subtype of ES is often characterized by a subcutaneous collection of epithelioid to spindled cells with large foci of central necrosis. The “proximal” subtype of ES is less common and tends to present in the trance, inguinal, genital soft tissues.6,7 The proximal subtype of ES tends to arise in the deep soft tissues and is usually characterized by large, “carcinoma-like” cells that are frequently mistaken for either melanoma or a malignant epithelial process. To date there have been a number of cytologic descriptions of the “classic” or distal variant of ES8–13 but relatively few reports of the proximal subtype of ES.14–16 In the following, we describe the radiographic, histologic, and cytologic features of one of these rare cases and compare our findings to those previously published. In addition, we illustrate the usefulness of a newer immunohistochemical marker (SMARCB1/INI1) as an adjunct to diagnosis of this rare tumor.
Case Report A 20-year-old male with no significant past medical history presented to his physician with a complaint of pain and numbness in his right arm. The duration of symptoms was 3 months. Also during this interval he noted a decrease in strength in his arm. On clinical exam he was noted to have an enlarged and firm axillary mass. Imaging was performed as part of his initial diagnostic workup. Nuclear magnetic resonance imaging of the chest revealed a large multilobulated mass involving the right Diagnostic Cytopathology, Vol. 43, No 10
859
Diagnostic Cytopathology DOI 10.1002/dc
PENDSE AND DODD
Fig. 1. Magnetic resonance imaging of proximal epithelioid sarcoma involving the soft tissue and lymph nodes in the axillary region.
supraclavicular, subpectoral, and axillary regions (Fig. 1). Also noted were multiple enlarged lymph nodes in the axillary region. Additional imaging revealed multiple pulmonary nodules, presumed to be metastatic disease. For initial diagnosis a fine-needle-aspiration (FNA) of one of the axillary nodes was performed. This was ultimately followed by an excisional biopsy of an axillary lymph node at an outside hospital. He was referred to our institution for treatment and began therapy; however, he was noncompliant and was lost to follow-up.
Cytologic Findings Ethanol fixed, Papanicolaou stained and air-dried Diff-Quik stained smears, along with a hematoxylin and eosin (H&E) stained cell block, were prepared from samples obtained from the right axillary mass by FNA. FNA smears were highly cellular with loosely cohesive clusters and dispersed large polygonal cells (Fig. 2). The cells had a plasmacytoid appearance, with an eccentric nucleus and moderate amount of cytoplasm. The nuclei were predominantly vesicular with one or more prominent nucleoli, and rare mitoses were seen. A cell block preparation prepared from aspirated material demonstrated polygonal cells in the background of lymph node and blood. Immunohistochemical (IHC) stains were performed and staining was positive for vimentin, CK8/18, cytokeratin AE1/3, and CD34. On the basis of the cytologic appearance and the IHC results, the lesion was diagnosed as “malignant epithelioid neoplasm, high grade.”
Fig. 2. (A) Diff-Quik stained smears of the fine-needle-aspirate from the right axillary lymph node shows the loosely cohesive and scattered cells in the background of lymphoid tissue and blood. A mitotic figure is present in the center of the filed. (B) On fixed, and Pap stained prep the epithelioid cells are enlarged with irregular nuclear outlines and prominent nucleoli. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
involvement of the lymph node, in an infiltrative pattern, by a metastatic neoplasm composed of epithelioid cells (Fig. 3). The tumor had a nodular growth pattern with small areas of necrosis. The cellular morphology was similar to that observed in the FNA sample. IHC stains performed on the excision specimen were again positive for vimentin, epithelial membrane antigen (EMA), and CD34 (membranous pattern). Additionally, INI1 staining was performed and demonstrated a loss of nuclear localization of the protein in the neoplastic cells (Fig. 4). On the basis of the morphologic appearance and IHC staining, a diagnosis of “Proximal-type epithelioid sarcoma” was rendered.
Histologic Findings
Discussion
A hematoxylin and eosin stained surgical biopsy specimen from the same site (right axilla lymph node) showed
Epithelioid sarcoma (ES) is a high grade, malignant neoplasm that presents in two distinct forms: a “classic”
860
Diagnostic Cytopathology, Vol. 43, No 10
Diagnostic Cytopathology DOI 10.1002/dc
PROXIMAL EPITHELIOID SARCOMA
Fig. 3. H&E stained sections of the right axillary node. Proximal epithelioid sarcoma, characterized by large cells with hyperchromatic nuclei with prominent nucleoli, has metastasized to the lymph node. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Fig. 4. INI1 shows a reverse staining pattern where the neoplastic cells show a loss of nuclear INI1 protein expression and normal cells are characterized by an “intact” nuclear staining pattern. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary. com.]
type, usually involving the superficial soft tissues of the distal extremities, and a “proximal” form, most often located in the pelvis, perineum, and genital tract. The classic form has a predilection for the flexor surfaces of the hand, fingers, and forearm. Classical ES often presents as a subcutaneous nodule or plaque like mass that is slow growing and painless. ES is an aggressive malignancy with clinical course often marked by multiple soft tissue recurrences, more proximal to the original lesion, and eventual metastases to the lung, brain, and bone. Interestingly, ES is one of the few sarcomas that tend to metastasize to regional lymph nodes. Treatment of ES is largely surgical and long term prognosis is still relatively poor. The proximal variant of ES shares many of the histologic, molecular, and cytogenetic features of the “classic” type but has a distinctly different clinical presentation. In the proximal subtype, the deeper soft tissues are affected and tumors form more of a solid mass. In addition, the proximal subtype is less common than the classic form (representing about one third of all ES).1 The median age of the proximal type patient is also somewhat older than the classical subtype (40 years vs.30 years). Unfortunately, the proximal subtype is associated with an even more aggressive course than the classic type of ES. Both proximal and classic forms of ES have a peculiar molecular abnormality than can be exploited for diagnostic purposes. ES typically shows multiple gains and losses of various chromosomes, as well as an abnormality at the hSNF5/SMARCB1/INI1 gene locus on chromosome 22.17 This results in an inactivation of the tumor suppressor gene. Inactivation correlates with loss of INI1 protein
expression by IHC and lack of expression of the marker can be used in the diagnosis of ES.18–20 ES is one of a number of neoplasms that demonstrate loss of INI-1 nuclear staining. Other tumors that typically show loss of nuclear INI-1 staining include rhabdoid tumor, myoepithelial tumors, and rare variants of renal carcinomas.20–26 Rhabdoid tumors, arising in either the central nervous system or in the soft tissues, are tumors of infancy, and not likely to be confused with ES.24 Myoepithelial tumors can show some clinical and histologic overlap with ES, but can be distinguished from the later by characteristic histology including the presence of extracellular matrix material. In addition, myoepithelial tumors will stain positive for S100 protein and frequently show EWSR1 gene rearrangement.25 Renal medullary carcinomas will also show loss of INI1 staining but these are lesions that arise in the kidney, and occur almost exclusively in individuals with sickle cell trait.26 Additionally, several entities need consideration while establishing a cytomorphologic and histologic differential diagnosis, including (metastatic) carcinoma, malignant melanoma, plasma cell myeloma, and other epithelioid sarcomas such as epithelioid angiosarcoma and epithelioid malignant peripheral nerve sheath tumors. A careful evaluation of the clinical and radiologic features along with a panel of appropriate immunostains will help arrive at an accurate diagnosis in the majority of cases. To date, the cytologic features of ES are only beginning to be well characterized and illustrated. The single largest series of the FNA findings of ES was published by Lemos et al. in 2008.9 In this study the authors described the features of ten cases of ES (seven primary, Diagnostic Cytopathology, Vol. 43, No 10
861
Diagnostic Cytopathology DOI 10.1002/dc
PENDSE AND DODD
three recurrent). Their findings included: single large cells with intact cytoplasm and enlarged nuclei with prominent nucleoli. They also described some cases showing an “eosinophilic” background material. A second series of nine cases by Cardillo et al.11 noted similar features. This series included two cases of tumors in the buttock region, probably representing the proximal variant of ES. These authors also commented on the presence of interspersed spindled cells and “granuloma-like arrangements” of cells, features not identified in all cases. Our case shows similarity to those previously reported including: a dispersed population of large round cells with irregular nuclear outlines and abundant cytoplasm.14–16 We did not note, however, the “rhabdoid” type of morphology described in the case reported by Gonzalez-Peramato et al.15 As PES represents an extremely rare lesion, it is important to recognize its characteristic cytologic features and how immunohistochemical staining for INI1 can be useful in facilitating a correct diagnosis.
References 1. Oda Y, Dal Cin P, Laskin WB. Epithelioid sarcoma In: Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F, editors. WHO classification of tumors of soft tissue and bone. Lyon, France: IARC Press; 2013. p 216–218. 2. Enzinger FM. Epithelioid sarcoma: a sarcoma simulating a granuloma or a carcinoma. Cancer 1970;26:1029–1041. 3. Chbani L, Guillou L, Terrier P, et al. Epithelioid sarcoma: A clinicopathologic and immunohistochemical analysis of 106 cases from the french sarcoma group. Am J Clin Pathol 2009;131:222–227. 4. Rekhi B, Gorad BD, Chinoy RF. Clinicopathological features with outcomes of a series of conventional and proximal-type epithelioid sarcomas, diagnosed over a period of 10 years at a tertiary cancer hospital in india. Virchows Arch 2008;453:141–153. 5. Miettinen M, Fanburg-Smith JC, Virolainen M, Schmookler BM , Fetsch JF. Epithelioid sarcoma: An immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol 1999;30:934–942. 6. Guillou L, Wadden C, Coindre JM, Krausz T, Fletcher CD. “Proximaltype” epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Clinicopathologic, immunohistochemical, and ultrastructural study of a series. Am J Surg Pathol 1997;21:130–146. 7. Hasegawa T, Matsuno Y, Shimoda T, Umeda T, Yokoyama R, Hirohashi S. Proximal-type epithelioid sarcoma: A clinicopathologic study of 20 cases. Mod Pathol 2001;14:655–663.
10. Kitagawa Y, Ito H, Sawaizumi T, et al. Fine needle aspiration cytology of primary epithelioid sarcoma. A report of 2 cases. Acta Cytol 2004;48:391–396. 11. Cardillo M, Zakowski MF, Lin O. Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases. Cancer 2001;93: 246–251. 12. Jogai S, Gupta SK, Goel A, Ahluwalia J, Joshi K. Epithelioid sarcoma. Report of a case with fine needle aspiration diagnosis. Acta Cytol 2001;45:271–273. 13. Zeppa P, Errico ME, Palombini L. Epithelioid sarcoma: Report of two cases diagnosed by fine-needle aspiration biopsy with immunocytochemical correlation. Diagn Cytopathol 1999;21:405–408. 14. Ikeda K, Tate G, Suzuki T, Mitsuya T. Fine needle aspiration cytology of primary proximal-type epithelioid sarcoma of the perineum: A case report. Acta Cytol 2005;49:314–318. 15. Gonzalez-Peramato P, Jimenez-Heffernan JA, Cuevas J. Fine-needle aspiration cytology of “proximal-type” epithelioid sarcoma. Diagn Cytopathol 2001;25:122–125. 16. Bajaj P, Aiyer H, Sinha BK, Jain M, Ashok S. Pitfalls in the diagnosis of epithelioid sarcoma presenting in an unusual site: A case report. Diagn Cytopathol 2001;24:36–38. 17. Modena P, Lualdi E, Facchinetti F, et al.. Smarcb1/ini1 tumor suppressor gene is frequently inactivated in epithelioid sarcomas. Cancer Res 2005;15:4012–4019. 18. Kohashi K, Izumi T, Oda Y, et al. Infrequent smarcb1/ini1 gene alteration in epithelioid sarcoma: A useful tool in distinguishing epithelioid sarcoma from malignant rhabdoid tumor. Hum Pathol 2009;40:349–355. 19. Hornick JL, Dal Cin P, Fletcher CD. Loss of ini1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 2009;33:542–550. 20. Le Loarer F, Zhang L, Fletcher CD, et al. Consistent smarcb1 homozygous deletions in epithelioid sarcoma and in a subset of myoepithelial carcinomas can be reliably detected by FISH in archival material. Genes Chromosomes Cancer 2014;53:475–486. 21. Hollman TJ, Hornick JL. INI1-deficient tumors: diagnostic features and molecular genetics. Am J Surg Pathol 2011;35:e47–e63. 22. Agaimy A. the expanding family of smarcb1(INI1)-deficient neoplasia: Implications of phenotypic, biological, and molecular heterogeneity. Adv Anat Pathol 2014;21:394–410. 23. Siagauke E, Rakheja D, Maddox CL, et al. Absence of expression of smarcb1/ini1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: An immunohistochemical study with implications for diagnosis. Mod Pathol 2006; 19:717–725. 24. Kodet R, Newton WA Jr, Sachs N. Rhabdoid tumors of soft tissue: A clinicopathologic study of 26 cases enrolled on the intergroup rhabdomyosarcoma study. Hum Pathol 1991;22:674–684.
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