Sayaka Moriguchi

Segmentectomy for reactive lymphoid hyperplasia of the liver : Report of a case

We report a case of reactive lymphoid hyperplasia (RLH) of the liver in a 72-year-old woman without any symptoms. To our knowledge, only 11 other cases of this disease have ever been reported. The lesion was found incidentally during a medical examination, as a hypoechoic mass in segment 3 of the liver on ultrasonography. The findings of computed tomography, magnetic resonance imaging, and angiography suggested a malignancy. Frozen section diagnosis of an intraoperative needle biopsy suggested malignant lymphoma, so we performed lateral segmentectomy of the liver. Macroscopically, the tumor was well defined, white, and firm. Microscopically, there was polymorphous lymphoplasmacytic infiltration, with various-sized and -shaped lymphoid follicles. Lymphocytic infiltration was also observed in the portal tracts around the nodular lesion. Immunohistochemical study revealed polyclonality, confirming a pathological diagnosis of RLH of the liver. We discuss the clinicopathologic characteristics of this unusual disease.

Disruption of Autosomal Recessive Hypercholesterolemia Gene Shows Different Phenotype In Vitro and In Vivo

We previously characterized the patients with autosomal recessive hypercholesterolemia (ARH) as having severe hypercholesterolemia and retarded plasma low-density lipoprotein (LDL) clearance despite normal LDL receptor (LDLR) function in their cultured fibroblasts, and we identified a mutation in the ARH locus in these patients. ARH protein is an adaptor protein of the LDL and reportedly modulates its internalization. We developed ARH knockout mice (ARH−/−) to study the function of this protein. Plasma total cholesterol level was higher in ARH−/− mice than that in wild-type mice (ARH+/+), being attributed to a 6-fold increase of LDL, whereas plasma lipoprotein was normal in the heterozygotes (ARH+/−). Clearance of 125I-LDL from plasma was retarded in ARH−/− mice, as much as that found in LDLR−/− mice. Fluorescence activity of the intravenously injected 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-LDL was recovered in the cytosol of the hepatocytes of ARH+/+ mice, but not in those of ARH−/− or LDLR−/− mice. Also, less radioactivity was recovered in the liver of ARH−/− or LDLR−/− mice when [3H]cholesteryl oleyl ether (CE)-labeled LDL was injected. In contrast, uptakes of [3H]CE-labeled LDL, 125I-LDL, and DiI-LDL were all normal or slightly subnormal when the ARH−/− hepatocytes were cultured. We thus concluded that the function of the hepatic LDLR is impaired in the ARH−/− mice in vivo, despite its normal function in vitro. These findings were consistent with the observations with the ARH homozygous patients and suggested that certain cellular environmental factors modulate the requirement of ARH for the LDLR function.

Atypical extraventricular neurocytoma

Extraventricular neurocytoma (EVN) is a rare brain tumor that poses diagnostic difficulty. Described herein is a case of atypical EVN arising in a 54‐year‐old woman. A well‐circumscribed lesion (3.0 × 3.0 × 3.0 cm) in the right parietal lobe showed diffuse proliferation of monotonous tumor cells with perinuclear clearing within a delicate fibrillary matrix similar to neuropil. Tumor also showed vascular proliferation and high mitotic activity. Immunohistochemically, these tumor cells were strongly positive for synaptophysin both in the neuropil and in the perinuclear cytoplasm, and were negative for glial fibrillary acidic protein and Olig2. Ki‐67 labeling index was 13.0% in the most stained areas, but accumulation of p53 was not observed. These findings were compatible with those of EVN with histological atypia. EVN should be considered as a candidate in the differential diagnosis of parenchymal brain tumor, especially oligodendroglioma. The important features are the delicate fibrillary matrix similar to neuropil, diffuse and strong immunoreactivity for synaptophysin, and negative immunoreactivity for Olig2. High proliferative activity without accumulation of p53 suggests that other factors are involved in oncogenesis of atypical EVN.

p16/CDKN2A FISH in Differentiation of Diffuse Malignant Peritoneal Mesothelioma From Mesothelial Hyperplasia and Epithelial Ovarian Cancer.

OBJECTIVES It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. METHODS p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. RESULTS According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. CONCLUSIONS Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected.

Autoimmunity Including Intestinal Behçet Disease Bearing the KRAS Mutation in Lymphocytes: A Case Report

We experienced the case of a 3-year-old male with a very rare combination of autoimmunity, including immune thrombocytopenia, recurrent Henoch-Schönlein purpura and intestinal Behçet disease. Exome sequencing of the patient’s peripheral blood mononuclear cells identified a KRAS G13C mutation. Interestingly, the KRAS G13C mutation was observed in T and B lymphocytes, as well as natural killer cells, but not granulocytes. Our case was completely phenotypically different from RASopathies and did not meet the criteria for Ras-associated lymphoproliferative disease or juvenile myelomonocytic leukemia. This is the first reported case in which the KRAS mutation existed only in the lymphoid lineage. Based on the findings of our case and the current literature, it is clear that the RAS mutation in lymphoid cells is tightly linked with various autoimmune symptoms. The presence of the RAS mutation in lymphocytes should be reconsidered as a pathogenesis in cases of autoimmunity.

Primary, solitary, adult T-cell leukemia / lymphoma of the descending colon

We herein report a patient with adult T-cell leukemia/lymphoma (ATLL) of the descending colon. A 64-year-old man was admitted to our hospital complaining of left lower abdominal pain. Endoscopic examination revealed an ulcerative tumor in the descending colon that was diagnosed as T-cell lymphoma by biopsy. Neither distant organ metastasis nor lymph node swelling was observed by radiographic examinations. Curative excision with left hemicolectomy and regional lymph node dissection was performed. Surgical sections contained ulcerative and superficially elevated lesions; these were continuous with each other. Histological examination revealed diffuse proliferation of medium-sized abnormal lymphoid cells. Immunohistochemically, these lymphoid cells were positive for UCHL-1/CD45RO and CD3 and negative for CD79a, indicating that the tumor was a primary malignant T-cell lymphoma of the descending colon. Integration of the proviral DNA of human T-lymphotropic virus type 1 (HTLV-1) was confirmed by Southern blotting analysis.

Neuroendocrine carcinoma of the posterior mediastinum arising from a foregut cyst

Neuroendocrine carcinoma of the posterior mediastinum is extremely rare. Described here is a patient with neuroendocrine carcinoma of the posterior mediastinum arising from a foregut cyst. A paravertebral mass detected in the posterior mediastinum of a 64‐year‐old man was spherical, solid and yellowish white. Some cystic or cleft‐like spaces were present. Microscopically, the lesion was composed of proliferating round or polygonal tumor cells in a diffuse, solid or trabecular fashion with extensive necrosis and high mitotic activity. Components of glandular epithelia and smooth muscle layers were evident in the cystic wall. Immunohistochemically, the tumor cells were positive for both epithelial and neuroendocrine markers, including pan‐cytokeratin, chromogranin A and synaptophysin. Neuroendocrine marker‐positive cells were also present in the glandular epithelium of the cystic walls. It was considered that posterior mediastinal neuroendocrine carcinoma arose from a foregut cyst. Malignant change within a foregut cyst is very uncommon. This is the first report of a neuroendocrine carcinoma of the posterior mediastinum arising from a foregut cyst.

Ovarian Seromucinous Borderline Tumor and Clear Cell Carcinoma: An Unusual Combination

Ovarian seromucinous borderline tumors (SMBTs) are rare. They architecturally resemble serous borderline tumors but are much more frequently associated with endometriosis. The coexistence of other tumors with seromucinous tumors is also extremely rare. Here, we report an unusual combination of bilateral ovarian SMBT and clear cell carcinoma associated with polypoid endometriosis of the colon, in a 62-year-old woman. There was no transitional lesion between the two tumors. Immunohistochemistry showed different staining patterns in tumor components. Seromucinous tumor cells were positive for estrogen receptor (ER) and progesterone receptor (PgR) but negative for Napsin A, p504S, and HNF1B. Clear cell tumor cells were positive for Napsin A and p504S and focally positive for HNF1B but negative for ER and PgR. Loss of ARID1A expression was not observed in SMBTs, clear cell tumors, or endometriosis. These findings suggest that these tumors arose from separate endometriosis foci and collided within the same ovary. To the best of our knowledge, this is the first case of this unusual combination of ovarian seromucinous tumor and clear cell carcinoma to be reported in the English literature.