CD34-Positive Spindle Cell Tumor With CTNNB1 Mutation: An Unusual Spindle Cell Variant of Sinonasal Glomangiopericytoma.

Sinonasal glomangiopericytoma is an uncommon mesenchymal tumor with a perivascular myoid phenotype, which is categorized as a borderline/low-grade malignant soft tissue tumor by the current World Health Organization Classification of Head and Neck tumors. Here, we present the case of a 53-year-old woman with an unusual spindle cell morphology of sinonasal glomangiopericytoma arising in the nasal cavity, mimicking solitary fibrous tumor. Microscopically, the tumor showed a cellular proliferation of spindle cells in fascicles including a focal long sweeping arrangement or whorls, or with a storiform growth pattern, associated with hemangiopericytoma-like gaping blood vessels embedded in a fibrous stroma. This arrangement of the spindle cells faintly indicated a solitary fibrous tumor rather than sinonasal glomangiopericytoma. Immunohistochemically, the tumor was positively reactive to not only beta-catenin (in the nuclei) but also CD34, although signal transducers and activators of transcription 6 was negative. Mutational analysis using Sanger sequencing detected a CTNNB1 mutation. We finally diagnosed the tumor as a sinonasal glomangiopericytoma, showing an unusual spindle cell variant. Such unusual spindle cell morphology with CD34-immunoreactivity potentially leads to an incorrect diagnosis of solitary fibrous tumor because such prominent fascicles including long sweeping structures, reminiscent of desmoid-type fibromatosis, have scarcely been described in the literature. Hence, careful morphological scrutiny using appropriate diagnostic adjuncts is necessary for correct diagnosis.

PDGFRB and NOTCH3 Mutations are Detectable in a Wider Range of Pericytic Tumors, Including Myopericytomas, Angioleiomyomas, Glomus Tumors, and Their Combined Tumors.

Pericytic tumors are subclassified as myopericytomas, myofibromas, angioleiomyomas, and glomus tumors according to the current World Health Organization classification. These pericytic tumors form a continuous morphologic spectrum, including those with combined morphology. However, to our knowledge, no widely accepted criteria for classifying tumors with combined morphology are available. Recent studies have identified platelet-derived growth factor receptor-beta (PDGFRB) gene mutations in a subset of myofibromas, myopericytomas, and myopericytomatoses but not in angioleiomyomas. NOTCH receptor 3 (NOTCH3) mutations have been reported in a subset of infantile myofibromatosis. To assess their potential role in classifying pericytic tumors, we investigated PDGFRB and NOTCH3 mutations in 41 pericytic tumors of variable morphology, including some combined forms. Our results show these mutations to be present in a variety of pericytic tumors, such as myopericytomas (PDGFRB, 3/11; NOTCH3, 4/11), myopericytomatoses (1/2; 1/2), myofibromas (3/6; 0/6), angioleiomyomas (2/13; 3/13), and glomus tumors (5/9; 1/9). Point mutations were identified in 3 tumors in PDGFRB exon 12 (Y562C, S574F, and G576S), 12 tumors in PDGFRB exon 14 (M655I, H657L, and N666K), and 9 tumors in NOTCH3 exon 25 (A1480S/T, D1481N, G1482S, T1490A, E1491K, G1494S, and V1512A). All PDGFRB mutations and NOTCH3 G1482S, T1490A, and G1494S mutations were classified as "deleterious/damaging" by ≥4 of 6 pathogenicity prediction tools in silico. Five-mutation-positive tumors, including 1 myopericytoma-angioleiomyoma, 2 myopericytomatoses-myofibroma, 1 myofibroma-myopericytoma and 1 angioleiomyoma-myopericytoma, were of combined morphology. Therefore, we found PDGFRB and NOTCH3 mutations to be detectable in a much wider variety of pericytic tumors than previously reported and confirmed myopericytomas, myofibromas, angioleiomyomas, and glomus tumors as members harboring PDGFRB or NOTCH3 mutations. Our results thus suggest that PDGFRB or NOTCH3 mutations are not useful for subclassifying members of the pericytic tumor family.

Potential pathogenetic link between angiomyofibroblastoma and superficial myofibroblastoma in the female lower genital tract based on a novel MTG1-CYP2E1 fusion.

Angiomyofibroblastoma and superficial myofibroblastoma are distinctive benign mesenchymal tumors occurring in the female lower genital tract. Despite their significant overlapping clinicopathologic features, including the presence of bland-looking spindle or oval cells with myofibroblastic or myoid differentiation, the tumors have been regarded as separate entities. Although subepithelial, hormone-sensitive mesenchymal cells of the female lower genital tract are considered as their potential common progenitor cells, their potential kinship or pathogenetic similarities remain elusive. Based on the identification of a novel RNA sequencing-based MTG1-CYP2E1 fusion transcript in an angiomyofibroblastoma index case, we investigated an additional ten samples of the tumor and its site-specific histological mimics, including eight superficial myofibroblastomas, four deep angiomyxomas, four cellular angiofibromas, three fibroepithelial stromal polyps, and eight non-site-specific mesenchymal tumors occurring in the female lower genital tract. Using reverse transcription-polymerase chain reaction, we showed that the MTG1-CYP2E1 fusion transcripts were consistently detectable in angiomyofibroblastomas (5/5, 100%) and often in superficial myofibroblastomas (3/5, 60%) but were not detected in the other examined site-specific or non-site-specific mesenchymal tumors. Our immunohistochemical experiments showed that CYP2E1, an isoenzyme belonging to the cytochrome P450 superfamily, exhibited increased positivity in tumors with MTG1-CYP2E1 than was observed in fusion-negative tumors (RR = 6.56, p = 0.001). The results of our study provide further evidence supporting the assertion that angiomyofibroblastoma and superficial myofibroblastoma represent phenotypic variants of site-specific mesenchymal tumors and share a common oncogenic mechanism.

Synchronous Occurrence of Ovarian Seromucinous Carcinoma and Endometrial Mucinous Carcinoma: A Case Report.

Endometrioid carcinoma is the most common histological type of concurrent synchronous cancers of the uterus and ovary. Here we report a case of synchronous seromucinous carcinoma of the ovary and mucinous carcinoma of the endometrium with a literature review. A 51-year-old multiparous female complained of irregular bleeding and shortness of breath. Computed tomography revealed a large pelvic mass that consisted of cystic and solid components, a tumor of the endometrium, and a large amount of pleural effusion. An endometrial biopsy indicated adenocarcinoma, and adenocarcinoma cells were found in the pleural fluid. The patient with advanced ovarian cancer or endometrial cancer with massive pleural effusion received three courses of neoadjuvant chemotherapy (NAC) with paclitaxel and carboplatin followed by interval debulking surgery (IDS). The NAC was effective, and IDS was performed with no gross residual lesions. The post-operative diagnosis was seromucinous carcinoma of the ovary in FIGO (2014) stage IVA (ypT3cNxM1a) and mucinous carcinoma of the endometrium in FIGO (2008) stage IA (ypT1aNXM0). Three courses of postoperative TC therapy were performed, and maintenance therapy with Bevacizumab is ongoing. The patient is well without evidence of recurrence, sixteen months after surgery.