Rare Epididymal-Derived Myoepithelial Carcinoma: A Case Report and Review of Literature.

Myoepithelial carcinoma (MC), also known as malignant myoepithelial neoplasm, is more common in the parotid glands of the head and neck. The main clinical manifestation is the growth of a nonspecific, painless mass at the primary site. We report the first case of MC derived from the epididymis. The current reports of non-parotid MC are still rare, and epididymal-derived MC has not been reported previously. Simultaneously, we explore the role of EWSR1 fusion as a predicting marker and further reveal the origin of MC to provide new ideas for its diagnosis and treatment.

Novel FUS-KLF17 and EWSR1-KLF17 fusions in myoepithelial tumors.

Myoepithelial (ME) tumors of soft tissue and bone display a heterogeneous histologic spectrum and in about half of the cases harbor EWSR1 gene rearrangements. Despite rare case reports, the prevalence of fused in sarcoma (FUS) gene abnormalities and its related fusion partners remains undetermined among ME tumors. Therefore, we screened 66 EWSR1-negative ME tumors for FUS abnormalities by fluorescence in situ hybridization (FISH). In an index FUS-rearranged case, 3'-rapid amplification of cDNA ends (RACE) was applied to identify the fusion partner. Results were further confirmed by reverse transcription-PCR, followed by FISH screening the entire cohort of FUS-rearranged and EWSR1-positive ME lesions lacking a known fusion partner. The correlation between genotype and clinicopathological features was also investigated. As a result, six (9%) FUS-rearranged cases were identified, spanning divergent age groups, tumor locations, and morphologic features. A novel FUS-KLF17 fusion was identified by 3'-RACE in an 11-year-old girl with a foot lesion associated with locoregional metastases. Three additional cases with FUS-KLF17 fusions were identified and one KLF17 rearrangement (6.3%) was found among the 16 EWSR1-positive cases tested. The KLF17-related ME tumors affected younger patients and often exhibited trabecular growth in a myxohyaline stroma, but this genotype did not correlate with a malignant phenotype. In conclusion, a small subset of ME tumors harbor FUS rearrangements, two thirds of them being associated with KLF17 fusion. FUS FISH analysis is recommended in EWSR1-negative lesions in which a ME diagnosis is suspected. KLF17 is also a rare gene fusion partner to EWSR1-rearranged ME tumors.

Human chorionic gonadotropin (hCG) up-regulates wnt5b and wnt7b in the mammary gland, and hCGbeta transgenic female mice present with mammary Gland tumors exhibiting characteristics of the Wnt/beta-catenin pathway activation.

Transgenic (TG) mice expressing human chorionic gonadotropin (hCG) beta-subunit under the ubiquitin C promoter, presenting with a moderately elevated level of LH/hCG bioactivity develop multiple neoplasms secondary to the endocrine abnormalities, including mammary gland tumors after the age of 9 months. The increased levels of circulating estradiol, progesterone, and prolactin of the TG females after puberty boost the lobuloalveolar development in the mammary gland resulting ultimately in the formation of estrogen and progesterone receptor-negative, malignant tumors. These tumors have a similar histopathology with those observed in TG mice with activated wnt/beta-catenin pathway, showing increased expression of beta-catenin, also a common finding in human breast tumors. Transdifferentiation is observed in mammary tumors of the hCGbeta TG mice, accompanied by abnormal expression of the Wnt genes in the tumorous and nontumorous mammary gland tissue. Specifically we found increased expression of Wnt5b in the TG mammary glands at the age of 3 months and up-regulation of Wnt7b and -5b in the subsequently appearing tumors. Importantly, hCG was found to up-regulate these wnt ligands in mouse mammary gland, independent of the changes in ovarian steroidogenesis. Thus, the hCGbeta-overexpressing TG mice represent a novel model that links enhanced hCG action to dysregulated wnt signaling in the mammary gland, resulting in beta-catenin-stabilizing mammary tumorigenesis. The novel finding of hCG up-regulating wnt7b and wnt5b could contribute to pregnancy-induced breast cancer in humans.

Interleukine-6 (IL-6) may be a link between myasthenia gravis and myoepithelioma of the parotid gland.

Myoepithelioma is a rare benign neoplasm of the salivary glands occurring more frequently in the parotids. Myasthenia gravis (MG) is a chronic, T-cell dependent, antibody and complement-mediated autoimmune neuromuscular transmission disorder. Interleukine-6 (IL-6) is an immune protein belonging to the family of the hematopoietins, liberated in response to infection, burns, trauma, and neoplastic diseases. It seems that an overproduction of IL-6 might play an important role in the pathophysiology of MG. Moreover, it has been discussed the possible role of IL-6 as a modulating factor either in proliferation or in differentiation of pleomorphic adenoma cell line into myoepithelioma. The authors present a rare case of parotid myoepithelioma occurred in a patient affected by myasthenia gravis and suppose a possible IL-6 mediated relationship between myasthenia gravis and parotid myoepithelioma.

Massive infra-clinic invasion of the facial nerve by a myoepithelial carcinoma of the parotid.

We report a new case of myoepithelial carcinoma of the parotid gland in an 8-year-old girl. This is the first case published in a child. The parotid tumour was slightly tender and measured almost 2 cm in diameter. There was no associated facial nerve paralysis despite surgical and histologic evidence of massive facial nerve infiltration. We performed total parotidectomy with resection of the intra-mastoid portion of the facial nerve completed with prophylactic lymph node dissection. Eight months after surgery, MRI revealed a deep-lying recurrence, which required reintervention. There has been no subsequent recurrence 18 months after surgery. Microscopic examination of operative specimens confirmed the diagnosis of parotid myoepithelial carcinoma with fusiform cells. Immunohistochemical markers were positive for cytokeratin, epithelial membrane antigen, smooth muscle actin, S-100 protein, anti-desmine and anti-vimentine. This difficult to diagnose tumour, which was individualised by the World Health Organisation in 1991, is considered a moderate to high-grade malignancy when it develops in a pleomorphic adenoma or appears de novo.

Myoepithelioma of the lacrimal gland: report of a case with potentially malignant transformation.

Myoepithelioma of the lacrimal gland is extremely rare and only four cases, one of which was malignant, have been reported in detail. The present report describes a case of lacrimal gland myoepithelioma in a Japanese male with histological features suggestive of potentially malignant transformation. The excised tumor consisted of two components, a central nodular component and a peripheral component surrounding the former. These components were separated by a fibrous tissue. Microscopically, both components were comprised almost entirely of spindle-shaped cells, but with some epithelioid cells containing glycogen granules. Extracellular spaces in the peripheral component were filled with eosinophilic materials with the occasional crystalloid structures, which were immunoreactive for collagen type I. Neoplastic cells were immunoreactive focally for vimentin and S-100, but negative for cytokeratins, epithelial membrane antigen, muscle actin, smooth muscle actin, desmin, myosin, and glial fibrillary acidic protein. The neoplastic cells in the central component showed nuclear pleomorphism and atypia with a higher frequency of mitotic figures, and higher labelings of proliferation markers than those in the peripheral component. Neither invasion, necrosis, nor hemorrhage was observed in the tumor. From these findings we proposed a diagnosis of potentially malignant myoepithelioma.