近藤 由佳

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.

There is limited data on BRAF V600E-mutant squamous cell carcinoma (SCC). We report three cases of SCC of the lung with a history of resected papillary thyroid carcinoma (PTC), showing p40 positivity, TTF-1 negativity, and PAX8 expression. While treated as lung SCC, metastatic thyroid carcinoma was unconfirmed due to absence of PTC recurrence, clinicopathologic features consistent with primary lung origin, and unavailable archival PTC pathology. BRAF inhibitors yielded only transient responses, and outcomes were poor. These cases underscore the diagnostic and therapeutic value of multigene testing in SCC, highlighting the need to integrate detailed clinical history into precision oncology strategies.

Some patients with cerebral amyloid angiopathy (CAA), which is characterized by amyloid β fibril deposition in cortical and leptomeningeal vessels, develop an inflammatory response, leading to CAA-related inflammation (CAA-RI). In such cases, histopathologically confirmed vasculitis is defined as amyloid β-related angiitis (ABRA). Here, we report the rare case of an 80-year-old woman who presented with anomic aphasia and mild right upper limb weakness. Magnetic resonance imaging revealed restricted diffusion in the subarachnoid space along the cerebral sulci and dura mater, mainly within the left parietal lobe. Additional imaging findings included lobar microbleeds, edematous white matter changes, and leptomeningeal and dural enhancement. Brain biopsy revealed vasculitis with amyloid β deposition, consistent with ABRA. Marked lymphoplasmacytic infiltration, which was present in the leptomeninges and the dural surface, was considered the cause of the subarachnoid diffusion restriction. Immunosuppressive treatment led to clinical and radiological improvement. As illustrated in this case, CAA-RI may present with atypical findings of subarachnoid diffusion restriction and dural involvement, and the recognition of these features, which can mimic rheumatoid meningitis and other inflammatory conditions, is important for differential diagnosis.

Bartonella henselae, a Gram-negative facultative intracellular bacterium, is the etiological agent of cat-scratch disease and also causes bacillary angiomatosis in immunocompromised individuals. Although the ability to promote vascular endothelial cell proliferation differs among Bartonella species, variations among strains within B. henselae remain unclear. Bartonella angiogenic factor A (BafA) and Bartonella adhesin A (BadA) have been identified as autotransporters of B. henselae that are involved in endothelial cell proliferation. Although strain-specific differences in the expression of BadA and the VirB/D4 type IV secretion system have been reported, BafA expression among B. henselae strains has yet to be examined. Therefore, the present study investigated the proliferation-promoting ability of 13 B. henselae strains from several sources in human umbilical vein endothelial cells (HUVECs). We identified BafA variants 1 and 2 based on the deduced amino acid sequences of its passenger domain. The recombinant proteins of both variants exhibited similar proliferation activity against HUVECs. However, BafA variant 2 strains showed cytotoxicity at a high bacterial inoculum in a direct coculture with HUVECs, which was attenuated in an indirect coculture. These strains, in contrast to BafA variant 1 strains, highly expressed BadA and exhibited bacterial aggregation. Based on a core genome SNP analysis of 50 B. henselae strains, the BafA variant types corresponded to clades 1-4. These results indicate that vasoproliferative traits differ among B. henselae clades based on the variant types. Therefore, this study provides a new conceptual framework in which the clades of B. henselae may predict their pathogenicity in humans.IMPORTANCEBartonella species including Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis cause vasoproliferative lesions. Their proliferation-promoting ability in vascular endothelial cells differs among Bartonella species; however, it is unclear whether these differences exist among B. henselae strains. We herein showed that B. henselae strains exhibited variable proliferation-promoting ability and cytotoxicity in vascular endothelial cells, which corresponded to the bafA gene variants possessed by the strains. The expression levels of Bartonella angiogenic factor A (BafA) and Bartonella adhesin A, as well as the degree of proliferation-promoting ability and cytotoxicity in endothelial cells, varied among the strains. A core genome SNP analysis of strains using whole genome sequencing data divided B. henselae strains into four clades, with each clade corresponding to BafA variants 1-4. These results suggest the differential vasoproliferative potency of B. henselae, with potential implications in clinical management, including risk stratification and predictions of the clinical course.

Epstein-Barr Virus (EBV)-positive inflammatory follicular dendritic cell sarcoma (EBV-IFDCS) is a rare tumor of low malignant potential. Abundant lymphocytes and plasma cells often infiltrate into this tumor tissue with lymphoid follicles and sarcoid-like granulomas, so that the differential diagnosis of this tumor includes inflammatory lesions such as IgG4-related disease, morphologically. This tumor typically arises in the spleen or liver, and shows follicular dendritic cell (FDC)-like immunophenotype. Here we presented a case of EBV-IFDCS arising in intrapancreatic accessory spleen, which was preoperatively considered as a pancreatic tumor. Immunohistochemistry revealed its fibroblastic reticular cell-like phenotype, namely alpha SMA, l-caldesmon, tenascin C, and transglutaminase II positivity, while FDC marker expression such as CD21 and clusterin was focal. Positivity for EBV-encoded small RNA in situ hybridization (EBER ISH) distinguished it from inflammatory lesions or conventional FDC sarcoma. The differential diagnosis of EBV-IFDCS is broad, ranging from non-neoplastic lesions to sarcoma, particularly when it arises in unusual sites. Therefore, careful gross and microscopic examination and adequate immunohistochemistry application including EBER ISH are important to diagnose it properly.

Mycoplasma hominis is a commensal pathogen normally found in urogenital tract of humans and has been associated with a wide variety of extra-genitourinary infections, such as mediastinitis, bacteremia, and septic arthritis, particularly in immunocompromised patients. Here, we present a case of a 48-year-old male, who had been treated with fingolimod for relapsing multiple sclerosis and presented with fever and right-sided hip pain following total hip arthroplasty. CT scan revealed localized fluid collection in the right quadriceps femoris muscle adjacent to the joint cavity of right hip. The percutaneously aspirated fluid grew M. hominis, which was also isolated from blood culture. With diagnosis of periprosthetic joint infection, the patient underwent surgical debridement with retained prosthesis and was treated with antimicrobial agents. Infected granulation tissues excised from the hip was observed under an electron microscope, which revealed electron-dense rounded structures contained in neutrophils, consistent with Mycoplasma particles. Fingolimod, an immunomodulatory drug that acts on the sphingosine-1-phosphate receptor and prevents the egress of lymphocytes from lymph nodes, might increase host susceptibility to a systemic M. hominis infection.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) can cause a wide variety of infections, ranging from skin and soft tissue infections to life-threatening invasive diseases such as necrotizing pneumonia and infective endocarditis. Here, we present a case of a healthy young female presenting with fever, headache and nausea, who was diagnosed with mitral valve infective endocarditis due to CA-MRSA and whose course was complicated by meningitis and multiple septic emboli. The causative MRSA strain belonged to sequence type 97 and harbored SCCmec Ⅳc but not lukS/F-PV genes. ST97, which is frequently isolated from livestock animals and known as a common lineage of livestock-associated MRSA, may cause invasive infection in the community.