南口 早智子

An 81-year-old man was treated with prednisolone, avacopan, and rituximab for microscopic polyangiitis and sulfamethoxazole/trimethoprim (SMX/TMP) and vonoprazan for prophylaxis. The liver enzyme levels were elevated 42 days after avacopan administration. Avacopan, SMX/TMP, and vonoprazan treatment were discontinued. A liver biopsy revealed vanishing bile duct syndrome. The patient was subsequently treated with ursodeoxycholic acid and glucocorticoid. Although vasculitis remained in remission, the patient ultimately died. Autopsy revealed persistent bile ductopenia and progressive liver cell injury confirmed by cytokeratin 7 positivity, severe cholestasis, and portal fibrosis. Further studies are required to elucidate associated mechanisms and risk factors.

BRAF p.V600E-mutant gliomas and glioneuronal tumors comprise a wide clinicopathological spectrum, yet the relationship between genomic alteration burden and histological grade remains incompletely defined. We analyzed 15 BRAF p.V600E-mutant gliomas and glioneuronal tumors across histological grades using the PleSSision Rapid sequencing platform. Single-nucleotide variants (SNVs) and copy-number alterations were assessed in parallel to characterize genomic alteration profiles. Low-grade tumors generally exhibited limited genomic alterations; however, a subset of low-grade tumors showed increased numbers of SNVs. High-grade tumors demonstrated more extensive genomic alterations, characterized predominantly by copy-number gains. A trend toward increased copy-number gains with higher WHO grade was observed. Homozygous deletion of CDKN2A was observed in pleomorphic xanthoastrocytoma, including both CNS WHO grade 2 and grade 3 tumors, and epithelioid glioblastoma. These findings indicate substantial genomic heterogeneity among BRAF p.V600E-mutant gliomas and glioneuronal tumors. While low-grade tumors are generally genomically quiet, a subset shows increased alterations, and high-grade tumors tend to acquire copy-number changes, highlighting the limitations of genomic event counts alone as a surrogate for malignant potential.

Lobular endocervical glandular hyperplasia (LEGH), a benign multicystic lesion that typically occurs in the upper uterine cervix, is regarded as a potential precursor lesion of gastric-type adenocarcinoma (GAS), including its well-differentiated form, minimal deviation adenocarcinoma (MDA). On MRI, LEGH characteristically shows the "cosmos sign," consisting of clustered small central cysts surrounded by larger peripheral cysts on T2-weighted images. However, MDA arising from LEGH can yield similar findings. Differentiation by MRI is therefore often challenging. This report describes two premenopausal women with MDA associated with previously diagnosed LEGH who underwent serial MRI follow-up. In both cases, T2-weighted images showing the cosmos sign revealed progressive enlargement of a central hypointense area with concomitant shrinkage of the surrounding cysts. Neither showed any readily apparent increase in overall lesion size. During follow-up after the initial diagnosis/conization, cytology remained negative for intraepithelial lesion or malignancy. In case 1, hysterectomy revealed MDA associated with previously diagnosed LEGH. The central hypointense area corresponded to tumor-associated reactive fibrotic stroma containing infiltrative glands with nuclear enlargement and mitoses. In case 2, hysterectomy showed deeply extending, morphologically diverse glands associated with reactive fibrotic stroma suspicious for invasion. The central hypointense area again corresponded to predominantly fibrotic stroma. These cases suggest that progressive expansion of a central low-signal-intensity area on T2-weighted images, accompanied by shrinkage of peripheral cysts, might constitute an early imaging sign of transition from LEGH to MDA, even without overall LEGH enlargement or worsening cytology. Such expansion should therefore be assessed carefully on follow-up MRI.

OBJECTIVE: Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms with a high propensity for local recurrence and extracranial metastasis. Although surgery and radiotherapy are the mainstays of treatment, systemic therapeutic options for recurrent disease remain limited. Pazopanib, a multitargeted tyrosine kinase inhibitor, has demonstrated clinical activity in extracranial SFTs; however, evidence in CNS SFTs is scarce. METHODS: We conducted a retrospective, single-institution study of patients with recurrent CNS SFTs treated with pazopanib. Clinical data, including prior treatments, imaging responses, treatment duration, and adverse events, were collected from medical records. Exploratory next-generation sequencing-based cancer panel testing was performed in two patients. RESULTS: Four patients with recurrent CNS SFTs were included. All had undergone prior surgical resection and radiotherapy. Pazopanib achieved partial response in one patient and stable disease in three patients, with treatment durations ranging from 7 months to over 2 years. One patient experienced disease progression after an initial period of response. Adverse events, including fatigue, gastrointestinal symptoms, and hypertension, were observed in all patients but were generally manageable with supportive care or dose adjustment. Exploratory molecular profiling identified various genomic alterations in two patients. CONCLUSIONS: In this single-institution retrospective series, pazopanib provided durable disease control with acceptable tolerability in selected patients with recurrent CNS SFTs. These findings support considering pazopanib as a systemic treatment option when further local therapies are not feasible, while highlighting the need for larger multicenter studies.