An autopsy case of adult-onset neuronal intranuclear inclusion disease with perivascular preservation in cerebral white matter.

Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disease characterized by appearance of eosinophilic hyaline intranuclear inclusions. While the main symptoms of adult-onset NIID are dementia or limb weakness, some patients present with encephalitic episodes and transient neurological symptoms. The pathophysiology of these acute, transient symptoms, however, remains unknown. Here, we describe an autopsy case of adult-onset NIID with progressive dementia and transient hemiparesis. The patient was a 70-year-old man without a relevant family history, and initially presented with progressive dementia. He then exhibited transient left hemiparesis at 75 years of age and died of ureteral cancer at 77 years of age. Neuropathological examination revealed the presence of multiple areas of focal spongiosis in the subcortical white matter and patchy myelin pallor of the white matter, as in previous reports. However, perivascular areas were preserved even in the damaged white matter. In addition, dense glial fibrillary acidic protein (GFAP)-immunoreactive astrocytic processes were observed in these areas. [Correction added on 23 January 2022, after first online publication: the preceding sentence has been corrected to improve readability.] GFAP immunohistochemistry revealed decreased density and morphological abnormalities of astrocytes in the affected white matter. These pathological findings might reflect blood-brain barrier impairment and dysregulation of blood flow, which may be related to the pathophysiology of the acute, transient symptoms observed in NIID.

Cellular cannibalism and consequent thrombocytopenia in a patient with bone marrow metastasis of malignant pleural mesothelioma: A case report.

Cellular cannibalism is a tumor activity where a cell is engulfed by another cell. This process promotes tumor cell survival under unfavorable conditions. The current report describes an extremely rare case of thrombocytopenia resulting from cellular cannibalism in a patient with bone marrow metastasis due to malignant pleural mesothelioma (MPM). A 77-year-old male presented with hemothorax and thrombocytopenia. He was diagnosed with MPM of the sarcomatoid cell type. However, his disease progressed rapidly and he died 11 days after admission. Bone marrow aspiration revealed metastatic MPM cells that had engulfed other blood cells. Accordingly, the observed thrombocytopenia was attributed to cellular cannibalism by metastatic MPM tumor cells. To the best of our knowledge, this is the first reported case of thrombocytopenia due to cellular cannibalism in a patient with this type of malignancy (MPM). The results suggested that although MPM rarely metastasizes to the bone marrow, bone marrow aspiration could be useful in such cases.

The First Autopsy Case of Fatal Acute Cardiac Failure after Administration of Carfilzomib in a Patient with Multiple Myeloma.

Carfilzomib (CFZ) improves progression-free survival for patients with relapsed or refractory multiple myeloma (MM) but has shown higher frequency of cardiovascular adverse events (CVAEs) than other proteasome inhibitors. We report the first autopsy case of acute death from cardiac failure shortly after administration of carfilzomib. A 74-year-old female was diagnosed with IgA MM after a 2-year period of smoldering MM. She was refractory to both bortezomib plus dexamethasone and lenalidomide plus dexamethasone therapies, so she subsequently received CFZ in combination with lenalidomide and dexamethasone. The day after the start of the therapy, she complained of severe dyspnea with a significant decline in left ventricular ejection fraction. Her acute cardiac failure rapidly progressed, and she died on day 7 of the start of CFZ. The autopsy showed invasion of inflammatory cells between the myocardial cells and very little myocardial necrosis. There was no obvious thrombus in the coronary artery of the heart, and no infarction or amyloid deposition was observed in the myocardium. Pathological findings of hypersensitivity myocarditis, a drug-induced cardiomyopathy, appeared to agree with this case except for absence of an eosinophilic infiltration of the myocardium. A CFZ-induced CVAE is generally considered reversible. However, rapidly progressing fatal heart failure like in our case is rare. To characterize CFZ-associated CVAE, further case collection is needed.

Lymphocyte-depleted classical Hodgkin lymphoma accompanied by myelofibrosis.

A 91-year-old male with fever of unknown origin was referred to our department. 18F-FDG PET/CT scan revealed a high FDG uptake in abdominal lymph nodes and multiple bones. The bone marrow biopsy showed fibrosis and atypical megakaryocytes, which were consistent with myelofibrosis. The patient died 28 days after admission and an autopsy was performed. The lymph nodes and bone marrow specimens revealed scattered Reed-Sternberg cells and a dearth of lymphoid cells with fibrosis. A final diagnosis of lymphocyte-depleted classical Hodgkin lymphoma (LDCHL) with bone marrow involvement was made. It is necessary to identify LDCHL during differential diagnosis for bone marrow fibrosis accompanied by lymphadenopathy.