Low-grade undifferentiated sarcoma with MEIS1::NCOA2-rearrangement primary to the lung: a case report.

BACKGROUND: MEIS1::NCOA2 is a rare fusion gene that has been recently described in a subset of spindle cell rhabdomyosarcomas and multiple low-grade undifferentiated spindle cell sarcomas predominantly arising in the genitourinary and gynecologic tracts with no specific line of differentiation. We present the first documented case of this neoplasm arising as a lung primary tumor. CASE PRESENTATION: A 74-year-old woman with a 40-year smoking history presented with a 2.1 × 1.7 cm lung nodule discovered on computed tomography (CT) scan. A biopsy and subsequent lobe resection were performed, as well as an extensive metastatic work up, which revealed no additional masses. No specific line of differentiation was found by immunohistochemical staining, and an RNA-based fusion panel revealed a MEIS1::NCOA2 fusion, at which point a diagnosis of Low-Grade Undifferentiated Sarcoma with MEIS1::NCOA2-Rearrangement was rendered. CONCLUSIONS: This report represents the first diagnosis of this tumor primary to the lung, and provides additional insight into the origin and localization of these rare tumors.

Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features.

INTRODUCTION: Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome. METHODS: Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease. RESULTS: Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course. CONCLUSION: Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.

Therapy-related myeloid neoplasms with normal karyotype show distinct genomic and clinical characteristics compared to their counterparts with abnormal karyotype.

Therapy-related myeloid neoplasms (t-MNs) are a complication of treatment with cytotoxic chemotherapy and/or radiation therapy. The majority of t-MNs show chromosomal abnormalities associated with myelodysplastic syndrome (MDS) or KMT2A rearrangements and are characterized by poor clinical outcomes. A small but substantial subset of patients have normal karyotype (NK) and their clinical characteristics and mutational profiles are not well studied. We retrospectively studied patients diagnosed with t-MN at three institutions and compared the mutational profile and survival data between t-MNs with NK and t-MNs with abnormal karyotype (AK). A total of 204 patients with t-MN were identified including 158 with AK and 46 with NK. NK t-MNs, compared to AK, were enriched for mutations in TET2 (p < 0.0001), NPM1 (p < 0.0001), ASXL1 (p = 0.0003), SRSF2 (p < 0.0001), RUNX1 (p = 0.0336) and STAG2 (p = 0.0099) and showed a significantly lower frequency of TP53 mutations (p < 0.0001). Overall survival (OS) was significantly lower in AK t-MNs as compared to NK cases (p = 0.0094). In our study, NK t-MNs showed a significantly better OS, a higher prevalence of MN-associated mutations and a lower frequency of TP53 mutations compared to their AK counterparts. The distinct clinical and mutational profile of NK t-MNs merits a separate classification.