Blue nevi are rare in the cervix and vagina. Melanocytes are not normally found in these sites and have been hypothesized to arise either from the Schwann cells of stromal nerves or from melanocytic precursors which have aberrantly migrated from the neural crest to rest in the Müllerian stroma. Because of their rarity (3 previous cases in the literature), vaginal blue nevi have not previously been studied with immunohistochemical and ultrastructural analysis. We describe 3 cases of blue nevus occurring in the Müllerian tract, 1 in the vagina and 2 in the endocervix. The vaginal lesion was seen during routine examination of a 40-year-old woman. The endocervical blue nevi were incidental findings in hysterectomies performed for leiomyomata and endometrial serous carcinoma in women aged 44 and 57 years, respectively. All 3 cases showed loose aggregates of cytologically benign, pigmented, dendritic spindle cells in the superficial stroma. They were immunoreactive for S100 and melan-A, but not HMB45. Ultrastructural analysis revealed numerous melanosomes, with no Schwannian features identified. Compared with the endocervical lesions, the vaginal nevus cells were more heavily pigmented, and on electron microscopy, a greater proportion of stage IV melanosomes were seen. We provide the first immunohistochemical and ultrastructural findings in a vaginal blue nevus, which confirm that it is of a similar nature to the endocervical blue nevi. Ultrastructurally, our results support a melanocytic rather than Schwannian origin for Müllerian blue nevi.

The ETV6/FLT3 fusion gene has been recently reported in association with myeloproliferative neoplasm with eosinophilia (MPN-Eo) and peripheral T cell lymphoma. Favorable clinical response to a targeted FLT3 tyrosine kinase inhibitor (FLT3 TKI) was noted. Here we report a novel phenotype associated with ETV6/FLT3 rearrangement, in a 38-year-old female with presentation of progressive lymphadenopathy. Lymph node biopsy showed mixed-phenotype acute leukemia (MPAL) with expression of T cell and myeloid markers. Bone marrow morphology was consistent with MPN-Eo and no evidence of MPAL. Karyotype analysis revealed 46, XX, t(12;13)(p13;q12). ETV6/FLT3 fusion was demonstrated by fluorescence in situ hybridization. This is the first report of ETV6/FLT3 rearrangement showing a phenotype of extramedullary T/myeloid MPAL arising in the setting of MPN-Eo. We suggest addition of this entity to the WHO category of “myeloid/lymphoid neoplasms with eosinophilia,” particularly given the possibility of clinical response to FLT3 TKI in MPAL, a disease usually associated with poor prognosis.

Aims: Loss of heterozygosity in chromosome 9p21, common in urothelial carcinoma (UC), typically involves deletion of CDKN2A and MTAP genes. MTAP loss is emerging as a promising therapeutic target and predictive biomarker in UC. This single‐centrre retrospective study examined the incidence of CDKN2A deletions and MTAP loss in muscle‐invasive bladder cancer (MIBC) and metastatic urothelial carcinoma (mUC), investigating their correlations with clinical, pathological, and genomic features, as well as patient outcomes.Methods: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed on 302 MIBC specimens and 63 biopsy‐proven metachronous urothelial metastases to assess CDKN2A deletions and MTAP protein expression.Results: CDKN2A homozygous deletion (HD), identified in 30.3% of MIBCs, and MTAP loss, found in 28.8% of MIBCs, were both significantly associated with the luminal‐URO subtype, FGFR3 mutations, and normal/wildtype p53 IHC (P < 0.05). Loss of MTAP expression was significantly correlated with CDKN2A HD, with 84.0% sensitivity, 92.3% negative predictive value (NPV), 96.3% specificity, and 91.9% positive predictive value (PPV). MTAP expression was 100% concordant between primary tumours and nodal metastases. Patients with MTAP loss had a higher incidence of visceral metastases (50%) compared to bone/soft tissue (35.7%) and nodes (14.3%). Mean progression‐free survival and overall survival were shorter for patients with MTAP loss, although not statistically significant.Conclusion: Our findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal‐URO subtype and FGFR3‐mutated, p53‐normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.