Proximal-type epithelioid sarcoma of the perineum: Calling attention of urologists


Atsuya Hikosaka md phd, Department of Urology, Kamo Hospital, 3-17 Motoshiro-cho, Toyota, Aichi 471-8505, Japan. Email:


Abstract  A subcutaneous mass in the perineum of a middle-aged man was excised and pathologically diagnosed at first as ‘undifferentiated carcinoma’ of unknown origin, which recurred 2 years later without any metastasis. Further histological evaluation ultimately established a correct diagnosis of ‘proximal-type epithelioid sarcoma’, a variant of rare epithelioid sarcoma. This type of tumor may confuse pathologists because its histological characteristics resemble undifferentiated carcinoma or malignant rhabdoid tumor. Frequent immunoreactivity of CD34, in addition to expression of keratins, epithelial membrane antigen and vimentin, provides strong support for the diagnosis of this rare neoplasm. Urologists should be aware that this sarcoma commonly occurs in the genital regions.


Epithelioid sarcoma (ES) is a rare, soft-part malignancy occurring in distal portions of the extremities of young adults. Recently a variant occurring in the proximal parts of older people has been suggested as ‘proximal-type’ epithelioid sarcoma (PES),1 which appears to confuse general pathologists because of its resemblance to undifferentiated carcinoma (UC). Here, we report a case of PES in the perineum followed up under an incorrect diagnosis for a long time. Similar cases may concern urologists.

Case report

A 46-year-old man visited our hospital complaining of perineal pain on erection for 2 months. Physical examination revealed a subcutaneous induration near the right side of the penis at the perineum, manifesting a broad, bean-size mass with relative hyperintensity to muscle on magnetic resonance imaging (Fig. 1). Surgical excision was carried out under the diagnosis of a perineal tumor. Microscopically, the excised specimen manifested a vaguely nodular pattern composed of sheets of large atypical epithelioid cells with mildly eosinophilic and large nucleoli. Immunohistochemically the tumor cells showed strong expression of cytokeratin (AE1/AE3) and vimentin. Immunoreactivity was negative for HMB45, S100 protein and alpha-smooth muscle actin (α-SMA). These findings resulted in an initial diagnosis of UC with sarcomatous change. Surgical margin was positive. Computed tomography and bone scintigraphy suggested no findings of metastases, and no lesion suggesting a primary site of the tumor was detected by endoscopy of the digestive and respiratory tracts. The patient had been followed up after adjuvant chemotherapy.

Figure 1.

Magnetic resonance imaging (T2-weighted image) demonstrates the perineal subcutaneous lesion adjacent to the right side of the corpus spongiosum (white arrow).

Two years after surgery, the subcutaneous lesion recurred at the same site. Re-excision was carried out and the histological findings of the surgical specimen were almost identical with those of the previous specimen (Fig. 2a). Although invasion to corpus spongiosum was observed (Fig. 2a), radiographic examinations revealed no metastasis.

Figure 2.

Pathological findings of the recurrent tumor. (a) Polygonal large atypical cells with prominent nucleoli are tightly proliferating (hematoxylin–eosin stain) with invasion to the corpus spongiosum (inset). (b) The tumor shows membranous immunohistochemical positivity for CD34.

As the clinical course of a relatively long time to recurrence without distant metastasis appeared unusual for the biological behavior of an undifferentiated carcinoma, further histological evaluation was considered. Most of the tumor cells were relatively large and showed epithelioid appearance, but some displayed rhabdoid features with cytoplasmic hyaline inclusion bodies (Fig. 3). The central necroses of the tumor were minimal. Additional immunohistochemical examination revealed strong positivity of CD34 (Fig. 2b) and epithelial membrane antigen (EMA). CD31 was negative. These findings, including the previous immunohistochemistry, together with the clinical course led to a corrected pathological diagnosis of PES.

Figure 3.

Tumor cells with rhabdoid features (small round cells with cytoplasmic inclusion body shown with yellow arrows) are observed (right side) next to the sheet of large tumor cells with abundant cytoplasm (left side).

The patient underwent adjuvant chemotherapy applying doxorubicin and ifosfamide and has been alive without disease for 15 months after the second surgery.


Epithelioid sarcoma is a rare soft tissue sarcoma typically presenting as a subcutaneous mass in distal portions (mainly the extremities) of adolescents or young adults. Histological findings are characterized by nodules of spindle and epithelioid tumor cells circumscribing hyalinization or necrosis (granuloma-like pattern).2 Proximal-type epithelioid sarcoma was reported for the first time in 1997 as a subtype of ES occurring in proximal parts of middle-aged and older people.1 It has a similar histological appearance to that of classical ES, but has distinct features including larger cells with prominent nucleoli resembling UC, epithelioid malignant peripheral nerve sheath tumor and malignant melanoma. Frequent rhabdoid features are also observed. Therefore, PES can easily be confused with such epithelioid or rhabdoid neoplasms, particularly extrarenal malignant rhabdoid tumor (ERMRT), and it is likely that a significant number of PES are misdiagnosed.1 Thus, PES appears to pose a diagnostic challenge for pathologists. Immunohistochemical examination provides a great contribution to the diagnosis of PES. Epithelial markers, including EMA and cytokeratin, are usually positive as well as vimentin. Although PES sometimes presents histological variations that can be confused with myogenic, angiogenic or neurogenic neoplasms, each specific marker like α-SMA, CD31, S-100 and HMB45 is negative. Positive immunopositivity of CD34, which is observed in approximately half of PES cases, is very useful to rule out UC and ERMRT.1,3

More than 40 cases of PES have been reported in the literature, indicating a more aggressive nature and poorer prognosis than classical ES.1,3–6 Approximately 60% have metastases mainly to the lung or the lymph node and 35% have local recurrence. Approximately half of the patients died of PES in 2–188 months (mean 39 months) after initial treatment. Only 12 cases are alive without disease for more than 10 months (mean 47 months). However, the rate of tumor-related death is lower than that of metastasis or recurrence, indicating the indolent but aggressive nature of PES.1,3

There has been no consensus on the treatment of PES. Most patients have undergone a combination of surgery, radiation and/or chemotherapy. In the present case, combination chemotherapy applying doxorubicin (20 mg/day, days 1–3) and ifosfamide (2 g/day, days 1–5) was carried out after re-operation. The Japanese Ministry of Health, Labour and Welfare recommends this regimen on the basis of many studies on chemotherapies for soft tissue sarcomas, reporting a response rate of 30–60% and significant improvement of recurrence or progression-free survival (but not cause-specific survival) as evidence ( Several studies have suggested the role of adjuvant radiotherapy for better local control.7

Urologists should keep in mind that PES has a predilection for proximal locations, particularly genital regions, which may result in a visit by most male PES cases to the urology office. In fact, more than 30% of the reported PES cases occurred in the perineum or the external genitalia.1,3,4,6 Therefore, PES should be taken into account as a differential diagnosis when a subcutaneous mass around the perineum or the external genitalia is observed.


We thank Dr Fikret Fatih Onol (Department of Urology, Marmara University School of Medicine, Istanbul, Turkey) for helpful information.