Clinicopathological features of five unusual cases of intraosseous myoepithelial carcinomas, mimicking conventional primary bone tumours, including EWSR1 rearrangement in one case

Abstract

Primary intraosseous myoepithelial tumours, including carcinomas are rare tumours. The concept of histopathological spectrum of these tumours is evolving. We describe clinicopathological and immunohistochemical features of five myoepithelial carcinomas, including molecular cytogenetic results in one case. There were five male patients within age-range of 8-40 years (median = 26). Four tumours occurred in the long bones, including two tumours, each, in the femur and fibula, respectively, while a single tumour occurred in the proximal phalanges. Tumour size (n = 3 cases) varied from 5.6 to 8.6 cm. On radiological imaging, most tumours appeared as expansile, lytic and destructive lesions. Two tumours appeared as sclerotic lesions. Two cases were referred with diagnoses of chondrosarcomas and a single case was referred with two different diagnoses, including an adamantinoma and an osteosarcoma. Histopathological examination in all these cases showed multinodular tumours comprising mostly polygonal cells, exhibiting moderate nuclear atypia and interspersed mitotic figures within a stroma containing variable amount of myxoid, chondroid, hyalinised and osteoid-like material. Three tumours revealed prominent squamous differentiation. By immunohistochemistry, tumour cells were positive for EMA (5/5), pan CK (AE1/AE3) (3/3), CK5/6 (4/4), CK MNF116 (1/1), S100 protein (5/5) and GFAP (3/5). The first tumour revealed EWSR1 rearrangement. The first patient, 10 months after tumour resection and a simultaneous lung metastatectomy, is free-of-disease (FOD). The second patient, 11 months after tumour resection is FOD. The third and fourth patients underwent wide resections and are on follow-up. The fifth patient underwent resections, including a lung metastatectomy. Primary intraosseous myoepithelial carcinomas are rare and mimic conventional primary bone tumours. Some primary intraosseous myoepithelial carcinomas display EWSR1 rearrangement. Squamous differentiation may be considered as an addition to their evolving histopathological spectrum. Immunohistochemical stains constitute as a necessary tool for arriving at the correct diagnosis in such cases, which has treatment implications. Surgical resection remains the treatment mainstay.

EWSR1‐PBX3 fused myoepithelioma arising in metatarsal bone: Case report and review of the literature

“…Immunohistochemistry can be helpful for diagnosis. Myoepithelial tumor of bone is immunoreactive for S100 and EMA, and various immunoreactivities for GFAP, p63, and pan‐CK have been reported . In the present case, the tumor cells were positive for S100, EMA, SMA, and calponin, supporting the diagnosis of intraosseous myoepithelioma.…”

“…In myoepithelial tumor of bone, most EWSR1 rearranged tumors have a bland histology including minimal cellular atypia, low level of mitotic figures, and no necrosis. However, two cases of malignant myoepithelial carcinoma with atypical features, such as significant nuclear atypia and increased mitotic count, were identified to harbor EWSR1 rearrangement . Two prior cases of EWSR1 ‐ PBX3 fused tumor and the present case also showed no significant atypical features suggestive of malignancy.…”

“…However, the criteria for distinguishing malignancy are not clearly defined, similar to the situation in soft tissue. Potential histologic findings that imply malignant myoepithelioma of bone include moderate to marked cytologic atypia, necrosis, and increased mitotic figures In our case, despite increased cellularity, the mitotic level was low and there was no evidence of significant nuclear atypia and necrosis. Moreover, the patient has shown no recurrence or metastasis for ten months after curettage.…”

“…as a translocation of t(1;22)(q23;q12) resulting in the fusion of EWSR1 – PBX1 and other various partner genes, including ZNF444, POU5F1 and KLF17 , with the EWSR1 gene . Molecular analysis has been documented in 23 cases of myoepithelial tumor of bone . Among these, the most common genetic abnormality is EWSR1 rearrangement, similar to myoepithelioma of soft tissue.…”

Rare Primary Malignant Bone Sarcomas

“…Primary myoepithelial tumors of bone are very rare. Microscopically, they do not differ from myoepithelial neoplasms of the salivary glands [22,23]. Most cases are composed of spindle to epithelioid cells organized in cords, strands, or trabeculae embedded in a myxoid or myxochondroid extracellular matrix.…”