Myxoepithelioid tumour with chordoid features: a clinicopathological, immunohistochemical and genetic study of 14 cases of SMARCB1/INI1‐deficient soft‐tissue neoplasm

Abstract

Myxoepithelioid tumour with chordoid features: a clinicopathological, immunohistochemical and genetic study of 14 cases of SMARCB1/INI1-deficient soft-tissue neoplasm Aims: Complete loss of SMARCB1/INI1 in soft-tissue tumours such as malignant rhabdoid tumour, epithelioid sarcoma, myoepithelial tumour of soft tissue and extraskeletal myxoid chondrosarcoma is often associated with high-grade malignancy and poor prognosis. The diagnosis is sometimes challenging, owing to histological similarities, so careful differential diagnosis is required. Therefore, soft-tissue tumours with complete SMARCB1/ INI1 loss could potentially include an unknown entity. Methods and results: We analysed 160 cases of SMARCB1/INI1-deficient soft-tissue tumour, and found 14 cases that were not classifiable into already existing categories and had common clinical and histological features. These involved two male and 12 female patients, ranging in age from 20 years to 61 years. The tumours were located in the the puboinguinal region (n = 13) and pelvic cavity (n = 1). Histologically, the tumours showed relatively uniform epithelioid to spindle-shaped cells with myxoid stroma. All tumours showed immunoreactivity for brachyury, epithelial membrane antigen, and progesterone receptor, and 12 of 14 cases did so for oestrogen receptor. Variable positive staining for a-smooth muscle actin, S100 and glial fibrillary acidic protein (GFAP) was seen. NR4A3 and EWSR1 gene rearrangements were not detected in 13 and 11 examined cases, respectively. Clinical follow-up data for the 14 patients showed that 13 were alive without disease and one had been lost to follow-up; four patients developed local recurrence and/or metastases. Conclusion:The designation 'myxoepithelioid tumour with choroid features' (METC) was proposed as a tumour with intermediate malignancy controllable with appropriate treatment, including the entity of myoepithelioma-like tumour of the vulvar region. METC represents a novel and independent subset that is histologically, biologically and clinically distinct from already existing SMARCB1/INI1-deficient soft-tissue tumours.

A Subset of SMARCB1 (INI‐1)‐deficient vulvar neoplasms express germ cell markers

“…43 Glypican-3 was also expressed in 4 of 13 cases of METC, two of which occurred in the vulva. 9 In our study, only one tumour expressed glypican-3, which was limited to foci with YST-like morphology. OCT3/4 represents a relatively sensitive marker for dysgerminoma/seminoma and embryonal carcinoma, but is invariably negative in YSTs.…”

“…A recent study has described the entity “myxoepithelioid tumor with chordoid features (METC),”, a SMARCB1‐deficient tumour with intermediate malignant potential occurring in the puboinguinal and pelvic region 9 . In this series of 14 cases, all METC showed immunoreactivity for brachyury, EMA, and PR 9 . Twelve tumours (86%) were positive for ER and five (36%) expressed S100 9 .…”

“…In this series of 14 cases, all METC showed immunoreactivity for brachyury, EMA, and PR 9 . Twelve tumours (86%) were positive for ER and five (36%) expressed S100 9 . Due to the significant morphologic and immunohistochemical overlap, it was proposed that MELTVR be included within the entity METC 9 .…”

“…Additionally, Kinoshita et al . demonstrated SALL4 positivity in 2 of 13 cases of METC 9 . Expression of SALL4 has been described in occasional ES arising at sites other than the vulva, ranging from 3–11% 39,44,47 .…”

“…9 Due to the significant morphologic and immunohistochemical overlap, it was proposed that MELTVR be included within the entity METC. 9 Immunoexpression of brachyury in MELTVR has not been described 8 ; the two presumed MELTVR in our series were negative for brachyury; however, both were focally positive for EMA and S100. S100 expression has not been described in MELTVR, 8 and additional studies are needed to better define this evolving group of neoplasms.…”