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A 5-year-old girl presented with headache and vomiting. Head computed tomography and magnetic resonance imaging showed a right frontal lobe tumor with marked calcification. The patient underwent resection surgery with suspicion of anaplastic ependymoma, and the tumor was gross totally removed. Pathological examination revealed areas of dense tumor cells with a high nucleocytoplasmic ratio and myxoid areas consisting of tumor cells with a round-shaped nucleus and eosinophilic cytoplasm. Perivascular pseudorosette, necrosis, circumscribed growth, and microcalcification were also observed. Immunohistochemistry demonstrated negative staining for glial fibrillary protein and epithelial membrane antigen. Diagnosis of a high-grade neuroepithelial tumor (HGNET) with BCL6 corepressor (BCOR) alteration was made based on pathological findings and internal tandem duplication in the exon 15 of BCOR. Although calcification on radiological and pathological examination is not typical, it would be essential to recognize that calcification could appear in HGNET-BCOR.

AimsMitochondrial cardiomyopathy (MCM) is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in the pathology examination. We aim to add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders.MethodsQuantitative analysis of mitochondria using electron microscopy and immunohistopathological analysis with respiratory chain enzyme antibodies were performed in 11 patients with hypertrophic or restrictive cardiomyopathy who underwent endomyocardial biopsy for possible MCM . Respiratory chain enzymatic assay in biopsied myocardium and genetic studies were also performed in all the subjects to define MCM.ResultsFour patients were diagnosed with MCM according to the recent criteria of mitochondrial respiratory chain disorders. Using electron microscopy with quantitative analysis, the volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared with the non-MCM group (p=0.007). Immunohistopathological results were compatible with the result of the respiratory chain enzymatic assay.ConclusionsPathological diagnosis of MCM could be confirmed by a quantitative study of electron microscopy and immunohistopathological analysis using the mitochondrial respiratory chain enzyme subunit antibody.

Lymphoepithelioma-like carcinoma is a poorly differentiated carcinoma with prominent lymphoid infiltration occurring in various organs but is exceedingly rare in the colorectal region. This malignancy is frequently associated with Epstein-Barr virus (EBV). Here we report a case of EBV-associated lymphoepithelioma-like carcinoma of the cecum in an 84-year-old male who presented with occult blood. In situ hybridization for EBV-encoded small RNAs (EBER) in an endoscopic submucosal dissection specimen showed that the tumor consisted of EBER-negative well-differentiated tubular adenocarcinoma and EBER-positive lymphoepithelioma-like carcinoma. Real-time PCR detected 7.16 copies of the EBV genome per cell in a sample microdissected from the latter component. Genotyping analysis demonstrated EBV genotype 1, and viral protein/transcript expression in the tumor showed EBV latency I. Expression of Ephrin receptor A2, a recently reported receptor for EBV, was demonstrated in the tumor cells by immunohistochemistry. To our knowledge, this is the first report of lymphoepithelioma-like carcinoma in the colorectal region showing a definite association with EBV infection.

Mitochondrial cardiomyopathy (MCM) is usually recognized as one of the phenotypes of systemic mitochondrial disease. However if there are no cardiac symptoms, it is difficult to make a definite diagnosis because of various cardiovascular phenotypes and no diagnostic criteria in pathological examination. To add myocardial pathology to the diagnostic criteria for mitochondrial respiratory chain disorders, which is the gold standard in the diagnosis of mitochondrial diseases, we performed quantitative analysis of mitochondria using electron microscopy and immunohistopathologic analysis with respiratory chain enzyme antibodies. Ten patients with hypertrophic or restrictive cardiomyopathy who had undergone endomyocardial biopsy were studied. Respiratory chain enzymatic assay and genetic study were performed and four patients were diagnosed with MCM. Using electron microscopy with quantitative analysis, volume density of mitochondria within cardiac muscle cells was significantly increased in the MCM group compared to the non-MCM group (p=0.013). Immunohistopathologic results were compatible with the result of the respiratory chain enzymatic assay. These advanced pathological tests can distinguish MCM from other cardiomyopathies. Results of immunopathologic study Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Practical Research Project for Rare/Intractable Diseases from the Japan Agency for Medical Research and Development, AMED.

Most metastatic lung tumors display well-defined, round, multiple nodular shadows, whereas the presence of diffuse ground-glass opacities on chest computed tomography generally suggests non-malignant conditions. Here, we report an unusual case of pulmonary metastasis from gastric cancer in which diffuse ground-glass opacities were observed in all lung segments. A 59-year-old man with a 3-month history of worsening chest pain and shortness of breath was referred to the pulmonary clinic. Chest computed tomography revealed low attenuation areas, suggesting emphysema, along with diffuse ground-glass opacities and interlobular septal thickening in both lungs. A transbronchial lung biopsy specimen revealed signet-ring cell carcinoma infiltrating the alveolar septa. Immunohistochemical staining of the cancer cells was positive for CDX-2, cytokeratin 7, and cytokeratin 20, and negative for surfactant apoprotein-A, TTF-1, and Napsin A. Gastrointestinal endoscopy revealed an ulcerative tumor in the stomach, and a biopsy from the tumor demonstrated malignant cells with similar morphology and immunophenotypes as those in the lungs. The final diagnosis was diffuse lung metastasis from gastric cancer. Our case shows that although multiple, well-defined nodules are typically considered to be the classic presentation of pulmonary metastasis, clinicians should also be aware of the possibility of pulmonary metastasis presenting as diffuse ground-glass opacities.

Intraocular lymphoma is a rare neoplasm that occurs only in the eyes and/or central nervous system. Diagnosis of intraocular lymphoma is difficult because its clinical manifestations mimic chronic uveitis. Pathological examination of the vitreous is one of the main diagnostic tools for intraocular lymphoma, but this is challenging due to the sparse cellularity and specimen degeneration. Here, we reviewed 33 cell block preparations from vitreous perfusion fluid in order to examine the significance of cytopathological findings for differential diagnosis using vitreous samples. The cases comprised 12 intraocular lymphomas and 21 non-lymphomatous diseases. Cytologically, vitreous samples from non-lymphoma cases showed lower cellularity than the lymphoma cases. Whereas vitreous material from cases with infectious endophthalmitis showed prominent neutrophilic infiltration, material from sarcoidosis cases showed infiltration of small lymphoid cells, especially CD4-positive T cells. On the other hand, lymphoma cases showed higher cellularity, with large, irregular and atypical lymphoid cells, frequent necrotic cells in the background, and less pronounced neutrophil infiltration. Immunocytochemically, 11 of the 12 lymphoma cases were of the B-cell phenotype and the remaining case was of the T/NK-cell phenotype. In conclusion, careful cytopathological examination or immunocytochemistry of vitreous material facilitates appropriate diagnosis of intraocular lymphoma.

Pleuropulmonary blastoma (PPB) is a rare malignant mesenchymal tumor. It is classified into 3 subgroups, and PPB type 1 is known to be a cystic lesion with good prognosis. Here, we report a case of PPB type 1 seen in a 1-year-old girl whose pulmonary cystic lesion had been followed-up as a congenital pulmonary airway malformation since neonate. The cyst had been diagnosed as congenital pulmonary airway malformation before surgery but the final diagnosis was type 1 PPB. The tumor had a somatic mutation in exon 25 of the DICER 1 gene whereas no germline mutation was found.

Background Desmoplastic small round cell tumor (DSRCT) is a rare soft tissue tumor that generally involves the retroperitoneum, pelvis, omentum and mesentery in younger patients. However, extra-abdominal DSRCT is very rare. Case presentation A 49-year-old Japanese man noticed a mass in the right parotid gland. Ultrasound examination revealed a solid tumor about 2 cm in diameter. Computed tomography (CT) of the whole body revealed no other tumors or lymph node swelling. Superficial parotidectomy was performed. Histologically, the tumor was composed of various-sized tumor cell nests in an abundant fibromyxoid and collagenous background. The tumor cells were small to medium-sized. Immunohistochemistry showed that the tumor cells were immunoreactive for epithelial markers and desmin. They also showed strong nuclear staining with a Wilms tumor 1 (WT1) antibody detecting the C-terminal region (C-WT1), but not the N-terminal region (N-WT1). We also performed 3′/5′ expression imbalance assay based on reverse transcription polymerase chain reaction (RT-PCR) to determine whether aberrant WT1 gene expression was present. This tumor was found to lack 5′-regional expression of the WT1 gene, as well as immunoreactivity with the N-WT1 antibody. Finally, fluorescence in situ hybridization (FISH) and RT-PCR analyses revealed the presence of a gene showing fusion between exon 7 of EWSR1 and exon 8 of WT1. The tumor was diagnosed as a DSRCT of the right parotid gland. The patient has been followed for 3 years without recurrence or metastasis. Conclusions Although DSRCT in the salivary gland is extremely rare, it should be included in the differential diagnosis of poorly differentiated salivary gland neoplasms, especially with a fibromyxoid background. Pathologists should bear in mind that DSRCT may occur in major salivary glands and should perform immunohistochemistry with appropriate antibodies, not only those against keratin and desmin, but also one detecting the C-terminal region of WT-1. Furthermore, molecular detection of EWSR1-WT1 fusion gene conclusively confirmed the diagnosis of DSRCT in this uncommon location.

Background IgG4-related disease is a new clinical entity frequently associated with swelling of the submandibular glands (SMGs). The long-term outcome of SMG swelling without steroid therapy remains unknown. Objective To examine whether swollen SMGs spontaneously regress without steroid therapy in the context of IgG4-related disease and to identify biomarkers that can predict the spontaneous regression of SMG swelling. Methods The SMG volume of 49 patients diagnosed with IgG4-related disease was calculated by measuring the axial and coronal planes of computed tomography scans. The change in SMG volume over time was measured and examined by treatment regimen, clinical data, and serum complement level. Results We found 28 of 49 (57%) IgG4-related disease patients to have swollen SMGs, with 15 of 20 (75%) of the swollen SMGs regressing without steroid therapy. The time required for the SMGs swelling to regress was significantly shorter in the steroid therapy group than in the no-steroid therapy group. Serum complement components at the initial visit were significantly lower in the regressed SMG group than in the nonregressed SMG group. Conclusion We observed 75% of swollen SMGs spontaneously regressed in patients with IgG4-related disease. The time required for the swollen SMGs to regress was longer in patients without steroid therapy than in those with steroid therapy. Serum complement level could be used as a predictor for the spontaneous regression of swollen SMGs in patients with IgG4-related disease.

Key Clinical Message Causes of intrauterine fetal death (IUFD) are uncertain in most placental mesenchymal dysplasia (PMD) cases. Our case showed high α‐fetoprotein levels in the maternal circulation, markedly dilated subchorionic vessels, and neonatal hemoglobin concentration of 8.4 g/dL, suggesting that fetal anemia may explain some adverse outcomes in PMD pregnancies.