Naoto Kuroda

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study.

Low‐grade tubular‐mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70‐year‐old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin‐1, epithelial membrane antigen, neuron‐specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense‐core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

Vascularization in tissue remodeling after rat hepatic necrosis induced by dimethylnitrosamine

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24u2009h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36u2009h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12u2009h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12u2009h after DMN injection and reached a peak in number at 36u2009h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.

Diagnostic pitfall of D2-40 in adenomatosid tumour.

classification, only six cases (18.75%) fitted within cribriform Gleason grade 3. Thus, with this new 2005 consensus classification system the percentage of cribriform Gleason grade 3 ranged between 8% and 15% of the total amount of cribriform tumour glands (without taking into account the remaining neoplastic patterns). The remaining cribriform glands were Gleason pattern 4, the former being closely related to the latter. In some cases, a change in morphology was observed in the serial sections performed for the immunohistochemistry. Specifically, these glands began to show angulated contours mimicking pattern 4 instead of pattern 3 (Figure 2). We have attempted to demonstrate, in agreement with the latest modification of the Gleason grading system, that cribriform Gleason grade 3 should be considered as grade 4, because both patterns are constantly observed in close relationship to each other, grade 4 being the predominant cribriform pattern (Figure 3). Therefore, Gleason pattern 3 appears to be a more regular and better circumscribed bidimensional image of a more complex and angulated three-dimensional glandular structure characteristic of a high cribriform grade.

Combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus

Hepatoid adenocarcinoma arising in the esophagus is extremely rare. To date, there are only 3 cases in the world English literature. We report the fourth case here. A 76-year-old Japanese man was admitted to our hospital because of the deterioration of nephritic syndrome. He presented with chest burn, and the endoscopic examination of upper digestive tract disclosed the tumor in the lower esophagus. The subtotal esophagectomy was undertaken because of esophageal cancer. The postoperative histologic examination showed the finding of combined tubular adenocarcinoma and hepatoid adenocarcinoma arising in Barrett esophagus. Immunohistochemically, hepatoid adenocarcinoma cells were positive for a-fetoprotein, hepatocyte, a1-antitrypsin, a1-antichymotrypsin, and CDX2, but negative for MUC5AC and MUC6. Esophageal hepatoid adenocarcinoma seems to be closely associated with Barrett esophagus and show the intestinal phenotype rather than gastric phenotype.

Zone 3 Predominance of Histopathological Features in Nonalcoholic Steatohepatitis

Nonalcoholic steatohepatitis (NASH) has a wide spectrum of histopathological features in terms of the necroinflammatory grading and the staging of fibrosis. Among these features, steatosis, necroinflammatory changes in the acinus (lobular hepatitis), and fibrosis show a definite zonal heterogeneity in liver acini; namely, a zone-3 predominance.Macrovesicular liver-cell steatosis is usually seen in zone 3. Ballooning degeneration and Mallory’s hyaline are predominantly observed in liver cells in acinar zone 3, and the activation of Kupffer’s cells and hepatic stellate cells (HSCs) is also present in zone 3. The basic and initial fibrosis that characterizes NASH also occurs in zone 3. This zone-3 predominance from the initial features through to the subsequent fibrosis in NASH suggests that injurious process(es) preferentially hit liver cells in zone 3. Based on the excessive deposition of neutral fat,cytochrome P450 (CYP) 2E1 may be induced, associated with the influence of other factors. The activated enzyme may generate free radicals, initiating lipid peroxidation. The aldehyde metabolites of lipid peroxidation may cause lobular hepatitis. Following the liver cell necrosis that occurs due to the inflammation, zone-3 fibrosis initially develops, associated with the activation of HSCs in that location. These sequential events that occur predominantly in zone 3 may, in part, reflect the complicated pathogensis of NASH.