Pathology International最新文献

A 50-year-old male with a pancreatic tail tumor underwent distal pancreatectomy. At 14 and 27 months after the primary surgery, metachronous liver metastases were identified and partial hepatectomies were performed for each. Pathologic findings of the primary pancreatic tumor were heterogeneous, but they essentially categorized into two components based on their cytologic features: (i) clear cell component and (ii) epithelioid cell component. The metastatic hepatic tumor was entirely composed of the epithelioid cell component. SMARCB1 expression was lost by immunohistochemistry and heterozygous deletion of SMARCB1 was identified by fluorescence in situ hybridization for both the primary and metastatic tumors. Targeted DNA sequencing of a metastatic hepatic tumor sample was performed and SMARCB1 loss was identified. Based on the morphologic, immunohistochemical, and molecular analyzes, the present case was difficult to classify into any of the existing entities. SMARCB1 deficiency might play a key role in the tumorigenesis.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by JC virus (JCV) infection. Although recognized as an AIDS complication in the 1980s, PML has emerged as a serious adverse event of immunosuppressive therapies since 2005, particularly disease-modifying drugs (DMDs) for multiple sclerosis (MS). PML can also occur in patients with collagenous diseases receiving steroid therapy or with age-related immunosuppression. In some cases, the etiology of immunosuppression remains unclear. These cases often present with early manifestations of PML, which, while common, are less well recognized, as PML was identified at more advanced stages in AIDS-related cases. Early diagnosis poses difficulty due to unfamiliar magnetic resonance (MR) images and low viral loads in cerebrospinal fluid (CSF), and brain biopsy may be conducted. This review summarizes the PML pathology identified through biopsy. Early cytopathological changes of JCV-infected cells, with the importance of dot-shaped inclusions associated with promyelocytic leukemia nuclear bodies (PML-NBs), are described. The variability of host immune responses, including PML immune reconstitution inflammatory syndrome (PML-IRIS), is addressed. The potential role of immune checkpoint inhibitors (ICIs), such as pembrolizumab, is also explored. Understanding the pathology of early PML helps to optimize diagnostic strategies and therapeutic interventions, ultimately improving prognosis.

Renal medullary carcinoma is a rare, high-grade carcinoma arising in the renal medulla, which is usually associated with sickle cell trait, and there are very few documented cases in the Japanese population. We report a case of renal medullary carcinoma, immunohistochemically defined as SMARCB1 deficient, in a 67-year-old Japanese woman without a history of sickle cell trait. Somatic mutation of SMARCB1 and an EML4::ALK fusion gene were identified by comprehensive genomic profiling. Computed tomography revealed metastatic lesions in the retrocaval lymph nodes, liver, and bronchus. Six cycles of the dose-dense methotrexate, vinblastine, adriamycin, and cisplatin-combined chemotherapy were completed after an ultrasound-guided percutaneous biopsy of the renal tumor. After chemotherapy, the size of the original tumor in the right kidney had decreased in size, as well as the other metastatic lesions.

We report the case of an 84-year-old male patient who was transferred to our hospital because of impaired consciousness and high fever, and died about 10 weeks after his fourth "coronavirus disease 2019" (COVID-19) vaccination. Autopsy revealed acute ischemic change with microhemorrhage and perivascular T-cell infiltration in the thalamus, pons, and cerebellum, which were considered to be related to neurological symptoms. There were dilatation of the right ventricle, accumulation of pleural effusion, and ascites, suggesting right heart failure. Although the patient had a negative COVID-19 polymerase chain reaction test, immunohistochemical analysis for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens (spike and nucleocapsid proteins) was performed to identify the cause of death. Surprisingly, only SARS-CoV-2 spike protein was detected in the thalamus, pons, and pituitary and adrenal glands. The presence of SARS-CoV-2 spike protein might have been due to vaccination rather than viral infection, because no SARS-CoV-2 nucleocapsid protein was detected. The spike protein in the central nervous system might have been related to the acute ischemic change, and that in the pituitary and adrenal glands may have been associated with right heart failure, possibly through dysfunction of the renin-angiotensin-aldosterone system.

The study investigated the expression of GATA3, a transcription factor involved in immune regulation, in tubo-ovarian carcinomas and its association with clinicopathological factors and prognosis. Immunohistochemical analysis was performed on 91 tubo-ovarian carcinoma samples to determine the presence of GATA3-positive inflammatory cells in the tumor microenvironment. A threshold of 10% or higher was considered a positive expression. The results showed that 46.7% of tubo-ovarian carcinomas exhibited positive expression of GATA3 in inflammatory cells. There was no significant difference in GATA3 expression between patients who received pre-surgical chemotherapy and those who underwent primary surgery. However, high-grade serous carcinomas had a significantly higher proportion of GATA3-positive inflammatory cells compared to other subtypes. Advanced-stage tumors (stage III) had a higher percentage of GATA3-positive inflammatory cells compared to stage II and I tumors. Patients with positive GATA3 expression had a significantly lower disease-free survival rate. However, there was no significant association between GATA3 expression and chemotherapy response score. These findings suggest that increased expression of GATA3 in mononuclear inflammatory cells is associated with higher grade, advanced stage, and increased risk of recurrence in tubo-ovarian carcinoma. This implies that heightened GATA3 expression negatively impacts anti-tumor immunity, tumor growth progression, and invasiveness in tubo-ovarian carcinomas.

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) exhibits hematological features that are indistinguishable from those of acute megakaryoblastic leukemia. However, TAM typically resolves spontaneously within several months postnatally. Some patients with TAM, however, develop severe clinical manifestations, which can lead to an unfavorable prognosis. TAM originates in utero through the acquisition of somatic GATA1 mutations, resulting in the loss of the full-length GATA1 protein and excessive production of the N-terminal truncated short isoform of the GATA1 protein (GATA1s). Herein, we report the pathological findings from an autopsy of a female stillbirth with TAM and DS, including an examination of her placental tissues. Immunohistochemical analysis revealed the expression of GATA1s, but not full-length GATA1, in CD42b-positive atypical immature megakaryocytes and blasts in the placental blood vessels. This confirms the diagnosis of TAM and suggests the utility of placental tissue for histological diagnosis. Additional unique findings from the autopsy specimens are discussed.