Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532-NUTM1 fusion: the expanding NUT cancer family.

NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis.

Soft Tissue Special Issue: Giant Cell-Rich Lesions of the Head and Neck Region.

Giant cell-rich lesions represent a heterogeneous group of tumors and non-neoplastic lesions, usually arising in bone, which harbor varying number of reactive osteoclastic-type multinucleate giant cells as a common feature. Among these entities, some are confined to the head and neck region (e.g., central giant cell granuloma and mimicking lesions, i.e., peripheral giant cell granuloma and cherubism) or show a relative predilection for this region (e.g., aneurysmal bone cyst and brown tumor of hyperparathyroidism), while others are rare but associated with distinct underlying disease (e.g., giant cell tumor of bone) or histology (e.g., tenosynovial giant cell tumor of the temporomandibular joint and phosphaturic mesenchymal tumor of the jaws) when occurring in the head and neck. Collectively, these lesions pose great challenge in the pathologic diagnosis, which often requires combinatory assessment from the clinical, histopathologic, and/or molecular aspects. This review provides a summary of pertinent clinical and pathologic features and an update of recent molecular and genetic findings of these entities. The considerations in differential diagnosis as well as the effects of the emerging therapeutic RANKL-antagonizing antibody denosumab will also be addressed.