Eosinophil-rich variant of nodal marginal zone lymphoma: a clinicopathological study of 11 cases.

AIMS: Tissue eosinophilia is commonly observed in T-cell and classic Hodgkin lymphomas, but rarely in B-cell lymphomas. Herein, we present the first report of a case series on nodal marginal zone lymphoma (NMZL) with tissue eosinophilia. METHODS AND RESULTS: All 11 patients in this study had nodal disease at primary presentation. The mean age at diagnosis was 64 years. The mean follow-up period was 39 months, and all patients were alive. Nine of the 11 patients (82%) showed no recurrence, but the other two patients experienced recurrence in the lymph nodes or skin. Marked eosinophilic infiltration was observed in all biopsied lymph nodes. Nine of the 11 patients had a preserved nodular architecture with expanded interfollicular areas. The other two patients showed diffuse lymphoma cell infiltration with effacement of nodal architecture. One of them was diagnosed as having diffuse large B-cell lymphoma transformed from NMZL because large cells accounted for >50% of the lymphoma cells and formed sheet-like patterns. Cells were positive for CD20 and BCL2 and negative for CD5, CD10, and BCL6. Some patients showed myeloid cell nuclear differentiation antigen (MNDA) positivity. All patients showed B-cell monoclonality via flow cytometry, southern blotting, and/or polymerase chain reaction (PCR). CONCLUSION: All patients showed distinctive morphological features and could be misdiagnosed with peripheral T-cell lymphoma due to their eosinophil-rich backgrounds. The predominance of B cells, absence of histiocytes, and high endothelial venules in the interfollicular areas are key factors for diagnosis. B-cell monoclonality is the most reliable evidence of differentiation. We designated this type of lymphoma as an eosinophil-rich variant of NMZL.

Extracranial metastatic solitary fibrous tumor/hemangiopericytoma expressing G-CSF and its receptor.

Although extracranial metastases are a relatively common phenomenon in patients with solitary fibrous tumors/hemangiopericytomas (SFTs/HPCs), factors involved in the mechanism underlying tumor growth and metastasis have not been identified. We report a case of extracranial metastatic SFT/HPC synthesizing granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor (G-CSFR). A 39-year-old man underwent a gross total resection of a well-circumscribed, dura-based, extracerebral primary tumor at the right frontal convexity. Neuropathologic evaluation of the tumor revealed an SFT/HPC characterized by staghorn vessels and a patternless architecture of hypercellular tumor cells, which had the eosinophilic cytoplasm and the nucleus immunoreactive for signal transducer and activator of transcription 6. He was treated with postoperative radiotherapy. He complained of fever and abdominal pain with systemic multiple metastatic tumors 10 years after the operation. The leukocyte count was 70,500/µL with 90.7% neutrophils (compared to 7400/µL at 39 years of age), and the serum G-CSF level was 283.0 pg/mL. Pathological examination of biopsy specimens of the liver and kidney tumors revealed the metastatic SFT/HPC. Immunohistochemically, G-CSF was localized in both the primary and metastatic SFT/HPC cells, whereas G-CSFR was localized only in the metastatic SFT/HPC cells. The tumors seemed to have the ability to produce G-CSF, even when G-CSF production is not clinically evident, suggesting that G-CSFR acquisition contributes to tumor growth, malignancy, and metastasis. In addition, there have been no reports showing G-CSF production in SFT/HPC cases. The influence of G-CSF is expected to be one of the factors related to SFT/HPC malignancy. Inhibitors of G-CSF could be a therapeutic agent for tumors that co-express both G-CSF and G-CSFR in an autocrine manner.

[Chronic Encapsulated Intracerebral Hematoma Associated with Arteriovenous Malformation, Shrinking after Feeder Embolization with Clinical Improvement:A Case Report].

Chronic encapsulated intracerebral hematoma(CEIH)with arteriovenous malformation(AVM)is rare. We report a case of CEIH shrinking after feeder embolization for AVM. A 60-year-old man experiencing headaches for 2 weeks was admitted to our hospital due to intracerebral hematoma detected by MRI. The hematoma was shown as a low-density mass lesion on CT scans. Angiography and enhanced MRI showed an AVM in the right temporal lobe associated with the CEIH. Mild disturbance of consciousness and headaches gradually worsened, as the CEIH grew. Before AVM resection, feeder embolization was performed. On the day after the embolization, symptoms improved and the CEIH shrunk in size. A week following the embolization, the AVM including the partial hematoma capsule was resected without neurological deficit. Previous literature showed similarities between CEIH and chronic subdural hematoma(CSDH)in clinical features and pathological findings of the capsule. This case indicated that feeder embolization might be a treatment option for CEIH with AVM, such as embolization of middle meningeal artery for intractable CSDH.

Rupture of the internal carotid artery pseudoaneurysm resulting from fungal sinusitis.

Although vasculitis due to infection with fungi, including Aspergillus, causes aneurysm formation, reports of internal carotid artery aneurysm formation resulting from fungal sinusitis are few. We report on a patient who experienced massive epistaxis from rupture of an internal carotid artery pseudoaneurysm, caused by fungal sinusitis. We treated the aneurysm with endovascular coil embolization, followed by endoscopic sinus surgery to remove the fungal mass. Intraoperative findings included a torn internal carotid artery and exposure of the coil to the sinus. Performing endoscopic sinus surgery before the embolization procedure would have increased the risks of massive intraoperative bleeding and mortality. Even after achieving hemostasis, serious sequelae, such as cerebral infarction, might occur. In this type of case, otorhinolaryngologists and neurosurgeons should collaborate, and an aneurysm should be treated before endoscopic sinus surgery. Although the treatment strategy for fungal internal carotid artery aneurysms is controversial, this case suggested the use of the embolization procedure followed by endoscopic debridement and antifungal therapy to treat a pseudoaneurysm of the internal carotid artery caused by fungal sinusitis.

Interleukin-6 as an enhancer of anti-angiogenic therapy for ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with elevated interleukin-6 (IL-6) expression, resistance to chemotherapy, and increased mortality. Although bevacizumab (Bev) is a widely used anti-angiogenic agent for EOC, the efficacy of Bev and the role of IL-6 in modulating angiogenesis in OCCC are unknown. We performed tube formation assays using human umbilical vein endothelial cells (HUVEC) cultured in OCCC cell-conditioned medium and using cells directly co-cultured with OCCC cells. We observed that IL-6 inhibition significantly mitigated the ability of Bev to impede tube formation in both cases. Furthermore, IL-6 blockade disrupted the anti-angiogenic efficacy of Bev and its concomitant anti-tumor activity. In addition, IL-6 inhibition resulted in a significant increase in angiopoietin-1 (Ang1) secretion and decreased vascular endothelial growth factor (VEGF) expression. Clinical specimens also exhibited this reciprocal relationship between IL-6 and Ang1 expression. Finally, depletion of Ang1 abrogated the effects of IL-6 inhibition on Bev activity, demonstrating that IL-6 supports the anti-angiogenic activity of Bev by suppressing Ang1 expression and promoting dependence on VEGF for angiogenesis. Altogether, our data suggest that OCCC tumors with high IL-6 levels are candidates for Bev therapy.