Pulmonary "Inflammatory Leiomyosarcomas" Are Indolent Tumors With Diploid Genomes and No Convincing Rhabdomyoblastic Differentiation.

Inflammatory leiomyosarcoma is a rare myogenic tumor with striking inflammatory infiltrates and a specific genomic pattern of near-haploidization despite exception(s). Recent studies demonstrated that inflammatory leiomyosarcoma shares substantially overlapping features with histiocyte-rich rhabdomyoblastic tumor, including expression of rhabdomyoblastic markers such as myogenin, MyoD1, and PAX7 and a high prevalence of genomic near-haploidization, suggesting that they represent a unifying entity, for which the term inflammatory rhabdomyoblastic tumor was coined. In this study, we identified 4 pulmonary tumors histologically typical of inflammatory leiomyosarcomas, all in men (aged 26 to 49), presented as slow-growing well-defined nodules ranging from 1.4 to 3.5 cm, and following uneventful postoperative courses. All tumors were positive for desmin immunostaining, while only 1 and 2 were focally positive for smooth muscle actin and smooth muscle myosin heavy chain, respectively. They showed no expression of myogenin, MyoD1, or PAX7 by immunohistochemistry or RNA sequencing. Copy number analyses by whole-exome sequencing (N=1), OncoScan single-nucleotide polymorphism array (2), and fluorescence in situ hybridization (1) revealed/suggested diploid genomes. Together with a previously reported case, all these pulmonary "inflammatory leiomyosarcomas" seemed clinically, pathologically, and genomically alike. Despite a superficial resemblance to conventional inflammatory leiomyosarcoma in somatic soft tissues (now preferably termed inflammatory rhabdomyoblastic tumor), they differ in the lack of convincing rhabdomyoblastic differentiation and genomic near-haploidization. Therefore, we propose that these pulmonary tumors probably represent a distinct entity, for which the exact line of differentiation, and perhaps the most suitable terminology to better reflect its nature, remains to be determined. The term inflammatory rhabdomyoblastic tumor seems inappropriate for this group of tumors.

Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis.

Malignant gastrointestinal neuroectodermal tumor (MGNET) is a sarcoma typically involving the gastrointestinal tract with neuroectodermal differentiation and EWSR1-ATF1/CREB1 fusions. Recently, rare MGNET cases were reported in extragastrointestinal sites. We identified 2 cases of MGNET arising in unprecedented laryngeal and intracranial locations, respectively. Both cases showed spindle and epithelioid tumor cells with amphophilic to clear cytoplasm and occasionally prominent nucleoli, arranged in solid, fascicular, and pseudoalveolar patterns. Case 1 exhibited moderate to marked nuclear atypia and focal intraepithelial component. In contrast, case 2 comprised predominantly low-grade epithelioid cells with extensive pseudopapillary structures. Both tumors showed an S100/SOX10-positive and HMB45/melan-A-negative immunoprofile as well as EWSR1-ATF1 fusion. A chief obstacle in diagnosing case 1 was the histologic and immunophenotypic resemblance to melanoma. The striking pseudopapillary architecture and the intracranial location of case 2 rendered differential diagnoses including meningioma and ependymoma. With the peculiar locations and morphology, these cases posed great diagnostic challenge.