岡部 直太

Immunoglobulin G4-related disease (IgG4-RD) is a recently identified systemic fibroinflammatory disorder affecting various organs throughout the body. IgG4-related lung disease is a relatively common manifestation in IgG4-RD and presents with 4 primary pulmonary patterns: nodular, ground-glass opacities, interstitial disease, and peribronchovascular thickening. Peribronchovascular thickening is a frequent pattern in thoracic IgG4-RD involvements. This case report describes bronchial obstruction as a consequence of IgG4-RD in a 65-year-old man with no personal or family history of autoimmune disease. Thoracoscopic segmentectomy was performed, which led to the diagnosis of IgG4-RD.

A 76-year-old woman with persistent diarrhea was referred to our hospital. She had purpura, peripheral eosinophilia (18,177/μL), and an elevated serum IgG4 level (819 mg/dL). Abdominal computed tomography revealed massive ascites and bowel edema. A skin biopsy of the purpura revealed leukocytoclastic vasculitis with prominent eosinophilic infiltration. Biopsies of the gastrointestinal mucosa revealed dense eosinophilic infiltration, indicating eosinophilic gastroenteritis (EG) associated with the hypereosinophilic syndrome. The number of IgG4-positive cells increased in the duodenal mucosa; however, the diagnostic criteria for IgG4-related disease (IgG4-RD) were not met. Whether or not EG with ascites is a manifestation of IgG4-RD warrants further investigation.

Ovarian mesonephric-like adenocarcinoma is rare and poorly understood, and preoperative diagnosis of this tumor with any diagnostic modality is challenging. Histological features can only be speculated through imaging. Herein, we present the case of a 64-year-old woman with primary ovarian mesonephric-like adenocarcinoma, characterized by a 13 cm pelvic mass detected via ultrasound. Further evaluation with magnetic resonance imaging showed low signal intensity in the solid component on T2-weighted images and high signal intensity on diffusion-weighted images, along with a smooth margin; these findings are consistent with those of previous reports. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, and partial omentectomy. Postoperative pathology confirmed mesonephric-like adenocarcinoma with positive peritoneal cytology. Immunohistochemical analysis showed a positive result for GATA-3 and a negative result for thyroid transcription factor-1. The patient was diagnosed with stage IC3 mesonephric-like adenocarcinoma, and adjuvant chemotherapy with paclitaxel and carboplatin was initiated. Mesonephric-like adenocarcinoma can present with distinct imaging features, including low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging, with a smooth solid margin; these imaging features may aid in the preoperative differentiation from other ovarian malignancies, such as serous or clear cell carcinomas.

Various studies have reported resistance mechanisms and treatment methods after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor treatment; however, treatment policies have not yet been established, and few cases have reported transformation to pleomorphic carcinoma (PC) as the resistance mechanism. Herein, we report the case of a 66-year-old woman who was diagnosed with Stage 4A lung adenocarcinoma (cT2bN0M1b) through bronchoscopic biopsy. Genetic profiling revealed an EGFR L858R mutation; therefore, osimertinib was administered as the first-line therapy and achieved a partial response. After 46 months of osimertinib treatment, the metastases remained under control; however, the primary tumor enlarged and was therefore resected. Pathological examination confirmed the diagnosis of PC. Genetic testing of the surgical pathology specimen showed that the EGFR mutation L858R was retained, and the patient was considered drug-resistant owing to the histologic transformation to PC. The patient continued osimertinib therapy and had no recurrence at 9 months postoperatively. Transformation to PC following osimertinib administration is rare, and we report this unique case. This study was approved by the Jichi Medical University Saitama Medical Center Ethics Committee (S24-073), and written informed consent was obtained from the patient.

A 53-year-old woman visited her district hospital complaining of right lower limb numbness 8 days after being diagnosed with COVID-19. She had been suffering diarrhea for 25 days before the hospital visit. Computed tomography showed multiple arterial and venous thromboses, and anticoagulation with a therapeutic dose of heparin was initiated. Acute aortic occlusion occurred on hospital day 5, and balloon thromboembolectomy was performed for revascularization of the lower limbs 9 hours after onset. Ulcerative colitis was diagnosed on postoperative day 7. With the anticoagulation and immunosuppression therapy, no thromboembolic event occurred postoperatively.

Squamous cell papilloma with elongated villous projections may occur in the hypopharynx and present with symptoms observable on physical examination.

Cytological detection of chordoma cells in the serosal cavity is challenging because of its rare presentation. Herein, we report a case of chordoma showing malignant pleural effusion accompanied by pleuropulmonary metastases in a 68-year-old woman. Cytological analysis was performed using pleural fluid obtained following thoracentesis. Conventional cytological staining demonstrated few clusters of large, atypical cells characterized by epithelial cell-like connectivity and rich cytoplasm with foamy and/or multivacuolar changes. The nuclei of these atypical cells were large and either round or oval with no conspicuous irregularities in the nuclear membrane. Periodic acid-Schiff staining of these atypical cells revealed fine granules in the cytoplasm. Giemsa staining showed foamy and/or multivacuolar cytoplasm in these cells, with metachromatic mucoid stroma in the surroundings. Immunocytochemistry analysis using cellblock showed these cells to be positive for broad cytokeratins, epithelial membrane antigen, S100 protein, vimentin, and Brachyury. To the best of our knowledge, this is the first case report in which chordoma cells were cytologically detected in pleural effusions. Our findings also suggest that conventional cytology combined with cellblock immunocytochemistry can increase the accuracy of chordoma cell detection in the serosal cavity.

Immune checkpoint inhibitors such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed death-1 antibodies are effective against malignant tumors. However, they induce unique adverse events known as immune-related adverse events. Hypophysitis is one of the most frequent immune-related adverse events of anti-cytotoxic T-lymphocyte antigen-4 therapies. However, there have been few reports describing the pathological findings of hypophysitis induced by anti-programmed death-1 antibodies. The present case is the first autopsy case of hypophysitis induced by nivolumab monotherapy, an anti-programmed death-1 antibody. Pathologically, lymphocytes infiltrated the anterior lobe of the pituitary gland, and the number of pituitary cells, especially adrenocorticotropic hormone-positive cells, decreased. However, necrosis and remarkable fibrosis were not observed. Immunohistologically, some pituitary cells expressed programmed death-ligand 1. Lymphocytes were predominantly CD8-positive T cells, and CD68-positive macrophages and CD20-positive B-cells were also observed. IgG and C4d were deposited on pituitary cells, but IgG4 (a subclass of nivolumab) was not detected. These findings indicate that type IVc and type II hypersensitivity mechanisms may occur in hypophysitis induced by anti-programmed death-1 antibodies and that the inflammatory mechanisms underlying hypophysitis induced by anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen-4 antibodies are different.

OBJECTIVES: Thymic epithelial tumors are the most common adult mediastinal tumors; however, their growth mechanism remains relatively unknown. Among the JAK/STAT pathway-related proteins, which control various intracellular events, STAT3 is deeply involved in cell proliferation. Constitutive activation of STAT3 and the resulting overexpression of cyclin D1 have been confirmed in various tumors, but have not been thoroughly investigated in thymic epithelial tumors. In this study, we immunohistochemically examined STAT3 activation, cyclin D1 expression, and JAK3 activation in thymic epithelial tumors and statistically analyzed their correlation with clinicopathological features. METHODS: Formalin-fixed paraffin-embedded specimens of 94 thymic epithelial tumors surgically resected at Kyorin University Hospital between 2005 and 2018 were included in this study. pSTAT3, cyclin D1, and pJAK3 were immunohistochemically examined, and the correlation with histology, Masaoka stage, and survival time was statistically analyzed. RESULTS: Cyclin D1 was found to be significantly overexpressed in the STAT3-activated group. This phenomenon was associated with histology and Masaoka stage. JAK3 was also activated in thymic epithelial tumors; however, JAK3 and STAT3 activation were not always correlated. Using survival time analysis, the STAT3-activated group, cyclin D1-expressed group, and JAK3-activated group had significantly lower progression-free survival times than those for both the non-activated and non-expressed groups. CONCLUSIONS: STAT3 activation may promote cyclin D1 overexpression in thymic epithelial tumors, and intracellular signaling pathways other than JAK3 may be involved in STAT3 activation. STAT3 activation, cyclin D1 overexpression, and JAK3 activation are biomarker candidates that indicate clinically poor prognosis.

PURPOSE: Well-differentiated liposarcoma, the most common subtype of liposarcoma, should be discriminated from benign lipoma. However, features on sonography for discriminating these two types of tumor have not been fully investigated. The present study was therefore aimed at clarifying differences in sonographic findings between well-differentiated liposarcoma and lipoma. METHODS: The study population comprised 23 cases of well-differentiated liposarcoma and 181 cases of lipoma. We investigated differences in sonographic appearance and pathological findings between the two types of tumor. RESULTS: Well-differentiated liposarcoma tended to develop more frequently in older patients and in the lower extremities including the gluteal region, compared with lipoma. Concerning sonographic findings, both tumors exhibited well-defined margins and heterogeneous internal echogenicity, including typical tiny striated hyperechoic lines. Well-differentiated liposarcoma was characterized by a higher frequency of the following findings compared with lipoma: (1) deep location, (2) irregular shape, (3) large diameter, (4) hyperechogenicity compared to surrounding tissue, and (5) presence of vascularity on Doppler sonography (p < 0.01 each). Notably, hyperechogenicity corresponded to the intermingled sclerosing component within the adipocytic component when sonographic findings were compared with those of pathology. CONCLUSION: The present study suggests that several sonographic findings including hyperechogenicity and presence of vascularity might be key features for discriminating well-differentiated liposarcoma from lipoma.