Fine-needle aspiration cytology of recurrent epithelioid sarcoma of the foot: Role of immonocytochemistry in definitive diagnosis.

Fine-needle aspirations (FNA) have played a crucial role in the diagnosis and follow-up of malignancies including sarcomas. However, relatively low specificity in the classification of sarcoma is the main limitation of FNA. Epithelioid sarcoma is a rare tumor of soft tissues. Very few individual case reports describing cytological features of epithelioid sarcoma have been documented in the literature. Here, we describe cytological features of epithelioid sarcoma with immunocytohistological correlation.

Introduction

Epithelioid sarcoma is a rare tumor of soft tissues recognized as a distinct clinicopathologic entity by Enzinger in 1970.[1] It has a predilection for distal extremities of young adults. Fibroma like, angiomatoid and rhabdoid variants of this tumor have been defined with characteristic cytomorphological features.[234] It can be confused histologically and cytologically with a variety of benign and malignant lesions including malignant melanoma, synovial sarcoma, squamous cell carcinoma, adenocarcinoma, and granulomatous inflammation.[5] Fine-needle aspiration (FNA) has been increasingly used in the preoperative diagnosis of soft tissue tumors due to high sensitivity and low cost.[6] FNA of sarcomas achieved a diagnostic sensitivity of 86.5% and specificity of 21% in one study.[7] The low specificity is a result of the high number of lesions sharing similar cytological findings. Here, we present a case of epithelioid sarcoma in a 65-year-old male, diagnosed cytomorphologically and confirmed with immunocytological studies done on the cell button.

Case Report

A 65-year-old male came to the surgery outpatient department with recurrent swelling on the dorsum of the foot operated 2 years back. The swelling was nodular, 4 cm × 3 cm in size and firm in consistency. The overlying skin showed scar of the previous operation. There was no significant inguinal lymphadenopathy. Systemic examination findings were noncontributory. Patient did not have previous histopathological reports. FNA was advised. Conventional cytology smears were prepared and stained with hematoxylin and eosin and Leishman stain. The cell button was also made, and the slides were kept for immunocytochemistry (ICC). Cytology smears were richly cellular and showed singly scattered and loosely cohesive small clusters of cells with mild anisonucleosis. The cells had vesicular nuclei with prominent nucleoli. Binucleated and multinucleated forms were noted [Figure 1a]. There was a moderate amount of eosinophilic cytoplasm. Many cells had rhabdoid features with eccentric nuclei. Some cells showed cytoplasmic extensions and trailing. Background showed red blood cells and macrophages. Provisionally the differential diagnosis of recurrent high-grade sarcoma and malignant melanoma of soft parts (clear cell sarcoma) was given. ICC was done on the slides prepared from cell button block. The tumor cells showed strong epithelial membrane antigen (EMA) (E29 Dako) membrane immunoreactivity [Figure 1b]. They showed strong PanCK (AE1/AE3) and vimentin (V9Dako) cytoplasmic immunoreactivity. There was the absence of immunoreactivity for S-100 and HMB45. So considering the clinical history, cytological features and ICC study, final diagnosis of epithelioid sarcoma was offered. Magnetic resonance imaging was done to see the extent of the lesion. A well-defined T2 hyperintense, T1 isointense enhancing lesion measuring 3.3 cm × 2.2 cm was noted along the dorsal aspect of the right foot in the subcutaneous plane. There was no obvious deeper extension of the lesion. Patient underwent wide local excision, and specimen was sent for histopathological examination. We received a skin covered tissue mass measuring 4 cm × 2 cm × 2 cm. On cutting open, the tumor was whitish, nodular measuring 2 cm in diameter. Microscopically it showed rhabdoid variant of the epithelioid sarcoma. Immunohistochemical (IHC) study done with EMA, PanCK, vimentin, HMB45 and S-100 confirmed the diagnosis. Margins and base of the lesion were free of the tumor.

Figure 1

(a) Photomicrograph of fine-needle aspiration showing singly scattered rhabdoid cells showing binucleation and multinucleation with prominent nucleoli (Leishman, ×400). (b) Immunocytochemistry done on cell button block showing strong membrane immunoreactivity for epithelial membrane antigen (ICC, ×400)

Discussion

Epithelioid sarcoma is an uncommon tumor that is more prevalent in adolescent and young adults.[1] However, no age group is exempted. Our patient was an old male. In the original description by Enzinger, epithelioid sarcoma was characterized histologically by a nodular arrangement of the tumor cells with an epithelioid appearance and a tendency to undergo central necrosis. The tumor cells were described as varying from large ovoid to polygonal with eosinophilic cytoplasm, to plump spindle-shaped cells. Chronic inflammation was usually seen around the lesion and was thought to simulate an inflammatory process. Most recently, three less common variants lacking the characteristics of the granulomatous appearance have been described as fibroma like, angiomatoid and rhabdoid.[234] Rhabdoid variant shows solid pattern with large cells. Cytologic description of an epithelioid sarcoma was first mentioned in 1974. Subsequently, several other authors have cited cytological features of additional 16 cases.[5] In general, the predominant pattern has been cells arranged singly or in small clusters. The cells with intercellular spaces, as described in the previous study were seen in our case.

Fine-needle aspiration has played a crucial role in the diagnosis and follow-up of malignancies including sarcomas.[6] However, relatively low specificity in the classification of sarcoma is the main limitation of FNA. Epithelioid sarcoma represents a perfect example of this limitation. It creates a challenge for the cytopathologist because of the wide range of nonneoplastic and neoplastic lesions with a similar appearance. The granulomatous appearance of classic epithelioid sarcoma can resemble a benign granulomatous process, especially in FNA of lymph node. Clinical history can be a diagnostic clue. Nuclear pleomorphism, singly scattered cells and immunocytochemical studies allow distinction of epithelioid sarcoma from a benign granulomatous process. Squamous cell carcinoma shares many cytologic features such as epithelioid appearance, presence of spindle cells, tadpole cells. One reliable distinguishing feature is the presence of well-defined cell borders associated with intercellular spaces in the epithelioid sarcoma, in contrast to squamous cell carcinoma which presents as syncytial clusters with no intercellular spaces. Other entities from which epithelioid sarcoma should be distinguished include adenocarcinoma, melanoma, and synovial sarcoma. Adenocarcinoma shares the same epithelioid features of epithelioid sarcoma, however, the presence of vacuolated cytoplasm and mucin, formation of acinar structures in adenocarcinoma is useful in the differential diagnosis from epithelioid sarcoma.

The cytological features of clear cell sarcoma (malignant melanoma of soft tissues) resemble that of epithelioid sarcoma, however, the difference in clinical presentation and ICC profile are crucial in the differential diagnosis. In clear cell sarcoma, the cells are mostly dispersed, but small groups of loosely cohesive cells are also present. The cells are polygonal or spindle-shaped. They have abundant pale cytoplasm and rounded nuclei with prominent nucleoli. Epithelioid sarcoma exhibits strong immunoreactivity with vimentin, cytokeratin, and EMA. It shows absence of immunoreactivity for S-100 and HMB45. This pattern of immunohistochemical staining was seen in our case.[8]

Thus, diagnosis of epithelioid sarcoma on cytomorphological features alone can pose a diagnostic dilemma. Cytomorphological features along with ICC analysis in an appropriate clinical setting help cytologist in arriving at precise diagnosis in lesions showing pleomorphic cells with epithelioid morphology. Our case highlights the role of ICC in the FNA in avoiding pitfalls in the diagnosis of epithelioid sarcoma.