Epithelioid Sarcoma

Abstract

Epithelioid sarcomas tend to occur in young adults (Fig. 14.1) either in distal locations (classic form) or in the perineum/groin area (so-called the proximal type). The classic form typically arises in the feet, lower extremity, digits, or forearms of younger men, and can be sometimes difficult to distinguish from reactive processes, such a granuloma annulare or an ulcer base. In contrast, the proximal-type epithelioid sarcoma exhibits a high degree of cytologic atypia, sometimes displaying rhabdoid morphology microscopically (Fig. 14.2) [1]. The classic form of epithelioid sarcoma is usually a slowly growing lesion, that metastasizes relatively early to lymph nodes, which will be positive in 1/3 to 1/2 of cases (Fig. 14.3) [2, 3]. The proximal type is often associated with a more aggressive clinical behavior, with local, regional, and metastatic disease developing over several years.

Epithelioid sarcomas tend to occur in young adults (Fig. 14.1) either in distal locations (classic form) or in the perineum/groin area (so-called the proximal type ). The classic form typically arises in the feet, lower extremity, digits, or forearms of younger men, and can be sometimes difficult to distinguish from reactive processes, such a granuloma annulare or an ulcer base. In contrast, the proximal-type epithelioid sarcoma exhibits a high degree of cytologic atypia , sometimes displaying rhabdoid morphology microscopically (Fig. 14.2) [1]. The classic form of epithelioid sarcoma is usually a slowly growing lesion, that metastasizes relatively early to lymph nodes , which will be positive in 1/3 to 1/2 of cases (Fig. 14.3) [2, 3]. The proximal type is often associated with a more aggressive clinical behavior, with local, regional, and metastatic disease developing over several years.

Fig. 14.1

Age distribution of adult patients with epithelioid sarcoma. MSKCC 7/1/1982–6/30/2010 n = 80

Fig. 14.2

Primary site distribution of adult patients with epithelioid sarcoma. MSKCC 7/1/1982–6/30/2010 n = 80

Fig. 14.3

T1-weighted MRI image of metastatic epithelioid sarcoma of the left upper extremity causing edema and multiple cutaneous and soft tissue implants

In the case of proximal-type epithelioid sarcoma, the differential diagnosis typically includes other high-grade malignancies, such as metastatic carcinoma and melanoma. Epithelioid sarcomas are EMA+ and generally positive for keratins. CA125 may be a serum tumor marker for this malignancy [4].

Nuclear hSNF5/INI1 expression is distinctly lost in these tumors, which may help excluding other diagnostic considerations (Fig. 14.4) [5, 6]. FISH analysis demonstrates the presence of large, homozygous SMARCB1 deletions in >90 % of both classic and proximal types of epithelioid sarcoma and can be used to distinguish from other tumors that show INI1 loss at protein level [7]. Primary therapy is resection, and given the frequency of nodal disease, sentinel node mapping seems advisable, with more complete node dissection in appropriate cases. Adjuvant radiation is generally not given except in tumors with positive or close margins as may be found proximally, and it is not clear if it is helpful in this histology in preventing recurrence, since local-regional relapse despite radiation and surgery is common.

Fig. 14.4

Microscopic appearance of proximal-type epithelioid sarcoma . (a) Solid sheets of epithelioid cells are seen, having ill-defined cell borders, eosinophilic cytoplasm, and macronuclei (H&E, ×400). (b) BAF47 immunohistochemistry demonstrating complete loss of INI1 staining expression in the tumor cells; an internal positive control is positive staining in blood vessels, not shown

Chemotherapy is not given in the adjuvant situation for this tumor given its relatively slow evolution and at-best modest response to chemotherapy in the metastatic setting. The slow moving nature of the tumor means that long exposures to chemotherapy (months) may be necessary to achieve evidence of tumor shrinking. We have observed at least minor responses to a variety of drugs used for epithelial tumors and sarcomas as well, such as doxorubicin , ifosfamide , vinorelbine , cisplatin , and others, but since people may need to be treated for many years for recurrence, parsimony is appropriate in patients with minimal symptoms (Table 14.1). A new concept arising is that of epigenetic therapy, which uses either HDAC inhibition or EZH2 inhibition to take advantage of the INI1 loss [8]. This has not been formally tested to date, however. Immune checkpoint inhibitors have not been formally tested in this diagnosis as of 2016, though there is an anecdote of activity in a case series [9].

Table 14.1 Systemic therapeutic recommendations for patients with epithelioid sarcoma

1 Outcome

Local disease-free survival is shown in Fig. 14.5 and disease-specific survival in Fig. 14.6.

Fig. 14.5

Local disease-free survival for adult patients with primary epithelioid sarcoma (all types). MSKCC 7/1/1982–6/30/2010 n = 48

Fig. 14.6

Disease-specific survival for adult patients with primary epithelioid sarcoma (all types). MSKCC 7/1/1982–6/30/2010 n = 48