Expression and localization of aromatase in human gastric mucosa : Immunohistochemical study using biopsy materials.

Parietal cells in the gastric mucosa are known not only as cells playing major roles in food digestion but also as cells bearing endocrine function. In addition to their production of gastrin and ghrelin, it has been recently revealed that these cells are also involved in the synthesis and secretion of estrogens with their expression of aromatase in experimental animals. Although aromatase activity has been detected in human gastric cancer cells and related cell lines, much less study has been done to ascertain the expression of the enzymatic activity in normal gastric mucosa. It has not been established which cell type is responsible for estrogen production in human gastric glands consisting of epithelial cells of several types. The aim of this study is to define the expression of aromatase by parietal cells in human gastric glands using immunohistochemical techniques. We retrieved formalin-fixed paraffin embedded materials of gastric biopsies from 16 patients (nine men, seven women). Colocalization of aromatase and H+/K+-ATPase ß-subunit indicated that positive cells are parietal cells, but not chief cells and mucous cells. Furthermore, immunoreactivity of aromatase was detected within gastric glands irrespective of age or sex. These results suggest that human parietal cells synthesize estrogens within gastric mucosa and subsequently secrete them to the portal vein via gastric vein, as they do in rats. These estrogens might influence liver functions in humans. The estrogenic effects related to liver dysfunction might also be attributed to them.

Myoepithelial carcinoma of the breast with focal rhabdoid features.

Myoepithelial carcinoma of the breast is extremely rare and only 33 cases have been reported in the English literature. Herein, we report a case of myoepithelial carcinoma of the breast with focal rhabdoid features. The patient was a 67-year-old woman, who presented with a lump of the left breast that rapidly grew to 3 cm in diameter within 3 months. Lumpectomy revealed a solid and whitish colored tumor, which was composed mainly of elongated spindle-shaped cells with mild atypia, focal necrosis, and infiltrative margin. In a small area of the lesion, ovoid tumor cells exhibited eccentric nuclei with centrally located nucleoli and plump cytoplasm including round eosinophilic inclusions, resembling a rhabdoid tumor. Immunohistochemically, both types of tumor cells exhibited a myoepithelial phenotype. MIB-1 index was 30%. The cytoplasmic inclusion of the ovoid cells exhibited immunopositivity for both vimentin and cytokeratin. From these findings, this tumor was diagnosed as a myoepithelial carcinoma with focal rhabdoid features. Although rhabdoid features have been reported in some types of malignant and benign tumors, this is the first report of such features in myoepithelial carcinoma of the breast.

Peripheral T-cell lymphoma arising from an intraglandular lymph node in the parotid gland: a case report and literature review.

T/NK-cell lymphoma of the salivary gland is rare. A 58-year-old man complained of a tumor mass in the left parotid gland region and he was diagnosed to have a left parotid tumor. The tumor was subsequently resected, revealing a diffuse growth pattern of medium to large sized atypical cells. The tumor was surrounded by fibrous connective tissue in the form of a capsule, and those were positive for CD3, CD4, CD5 and CD30, but negative for Bcl2, CD8, CD10, CD15, CD20, CD25, CD56, CD79a, CD246, EMA, granzyme B, TdT and TIA-1. There was no molecular evidence of Epstein-Barr virus (EBV) infection. It was diagnosed as peripheral T-cell lymphoma (PTCL) arising from an intraglandular lymph node in the parotid gland. In conclusion, Only 17 cases of primary T/NK-cell lymphoma of the salivary glands have been recorded until now, and the characteristics of these are not clear yet. Additional study is needed.

Pyloric gland metaplasia/differentiation in multiple organ systems in a patient with Peutz-Jegher's syndrome.

Peutz-Jegher's syndrome (PJS) involves multiple organ systems and the development of hamartomatous, metaplastic, or neoplastic lesions of different cell lineages. Among them, glandular lesions are the most common, but their properties are obscure. We report here a 53-year-old woman with PJS who developed multiple hamartomatous polyps in the jejunum and mucinous glandular lesions in multiple organ systems: glandular metaplasia in the urinary bladder; lobular endocervical glandular hyperplasia in the uterine cervix; mucinous metaplasia in the right fallopian tube; mucinous adenoma in the left ovary. Histological and immunohistochemical analyses disclosed that all of the intestinal and extra-intestinal lesions were associated with pyloric gland metaplasia/differentiation across the organ systems. In the general population, the organs described above rarely or infrequently show pyloric gland phenotype, to say nothing of trans-organ involvement. It is strongly suggested that commitment to pyloric gland metaplasia/differentiation is closely associated with PJS.

A case of serous cystic tumor, which recurred with severe acute pancreatitis.

A 76-year-old woman with serous cystic tumor (SCT) was admitted to our hospital with abdominal pain and was given a diagnosis of severe acute pancreatitis. Infusion of intravenous protein inhibitor and continuous hemodiafiltration (CHDF) were started and she was placed on a respirator, but she died on the 6th day after diagnosis. On autopsy, each SCT cyst showed evidence of hemorrhage. We supposed that the growth of the SCT after hemorrhage compressed the main pancreatic duct and caused severe acute pancreatitis. SCT is benign, and there are no standard treatments. During follow-up of patients with SCT, we should consider the risk of severe acute pancreatitis.

Expression of BAFF-R and TACI in reactive lymphoid tissues and B-cell lymphomas.

AIMS: The receptor for B-cell-activating factor belonging to the tumour necrosis factor family (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) have been established as binding molecules to BAFF. The aim of this study was to determine the pathological diagnostic roles and clinical significance of these BAFF-binding receptors in B-cell neoplasms. METHODS AND RESULTS: Expression of BAFF-R and TACI was examined immunohistochemically in reactive lymphoid tissues and B-cell lymphomas including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (MZBCL) and plasma cell myeloma (PCM). In reactive tissues BAFF-R was expressed exclusively in the cells of the mantle zone and within the germinal centres (GCs), whereas TACI appeared positive in the scattered cells in extrafollicular areas. There were variable patterns of expression of BAFF-R and TACI amongst the different types of B-cell lymphomas (MCL and FL: BAFF-R+TACI-; PCM: BAFF-R-TACI+; DLBCL and MZBCL: variable expression). Reverse transcriptase-polymerase chain reaction studies supported these results. The overall survival of the BAFF-R+ DLBCL group was significantly better than that of the BAFF-R- group. CONCLUSIONS: These results indicate that the assessment of expression of BAFF-binding receptors aids subclassification and prognostication of DLBCL.

Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.

We report a patient with primary histiocytic sarcoma of the spleen associated with prominent hemophagocytosis. Although thrombocytopenia, probably due to hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of platelets, and splenic irradiation, partial splenic embolization was effective and facilitated splenectomy for a diagnosis. The majority of the spleen showed necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible. The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were negative for lymphoid, myeloid, and epithelial cell markers. CD163, a monocyte/macrophage-specific molecule, was positive in only some of them. Despite multiagent chemotherapy, the patient died of the disease, showing a rapidly progressive clinical course. Although the preoperative diagnosis of primary splenic histiocytic sarcoma is difficult, it has been confirmed in patients with splenomegaly of unknown etiology that clinicolaboratory features suggestive of hemophagocytosis may be important clues suggestive to the disease. CD163 expression by neoplastic cells could be confirmed only after careful observation, because the molecule may only be seen in some of the neoplastic cells.

A case report of proliferative glomerulonephritis with monoclonal immunoglobulin M-kappa deposits without associated lymphoproliferative disorder or detectable paraproteinemia.

A 53-year-old man presented with proteinuria and hematuria. No significant abnormality was detected in his physical examination or laboratory tests, including evidence of paraprotein in serum and urine. Renal biopsy revealed mesangial proliferation, thickened glomerular basement membranes, and spike formation. Immunofluorescence revealed deposition of immunoglobulin (Ig) M heavy chain, kappa (κ) light chain, and complement component C3 along capillary walls in the glomeruli. Light chain staining indicated significant restriction, because only κ chain, not lambda chain, was present in glomeruli. Aggregated electron dense deposits were observed in the subepithelial area and within the lamina densa on electron-microscopic examination. Cryoglobulinemia and amyloidosis were ruled out. Clinically, steroid therapy was not initiated due to patient preference, and the only prescribed medication was an angiotensin II receptor blocker. At the approximately 3-year follow-up, estimated glomerular filtration rate had decreased very mildly. The present case demonstrates that deposition of monoclonal IgM-κ may be associated with membranoproliferative glomerulonephritis-like changes in the glomeruli. Although no underlying hematological abnormality or paraproteinemia was observed in this case within the range of limited clinical examination, the patient's condition is consistent with proliferative glomerulonephritis with monoclonal IgM deposits, similar to the recently established proliferative glomerulonephritis with monoclonal IgG deposits. Further elucidation of the pathophysiology and effective treatments of the disorder should be expected in the future through the accumulation of similar cases.

Maternal vitamin B12 deficiency affects spermatogenesis at the embryonic and immature stages in rats.

To evaluate the role of cobalamin (Cbl) on spermatogenesis, the effect of dietary vitamin B(12) deficiency on early spermatogenesis was histologically investigated in male fetuses and newborns in the first filial generation (F(1) males) of rats. There was no difference in the number of gonocytes and supporting cells of Sertoli in the gonad in male fetuses on day 16 of gestation and in the testes in F(1) males at 0 days of age between vitamin B(12)-deficient (VB12-D) and vitamin B(12)-supplemented (VB12-S) groups. However, at 21 days of age, a decreased number of spermatogonia and no spermatocytes were observed in the VB12-D group. Numerous TUNEL positive cells were located among spermatocytes of the spermatogenic epithelium. The ultrastructural features examined using transmission electron microscopy were considered to be indicative of apoptosis. The incidence of seminiferous tubules having apoptotic cells was 51.5% in the VB12-D group. At 60 days of age, aplasia of the spermatids and spermatozoa was detected in the VB12-D group. In the connective tissue between the seminiferous tubules, many interstitial Leydig cells and blood vessels were observed in the VB12-D group, as compared with the VB12-S group. These changes produced by vitamin B(12) deficiency can be reversed by providing a VB12-S diet after weaning at 21 days of age. From these findings, such a vitamin B(12) deficiency during gestation and lactation could affect the germ cells and especially damage spermatocytes in F(1) male rats, which indicates that Cbl may be an essential constituent in the meiosis of spermatogenesis.

Early Improvement in Marrow Fibrosis Following Haploidentical Stem Cell Transplantation for a Patient with Myelodysplastic Syndrome with Bone Marrow Fibrosis.

The prognosis for myelodysplastic syndrome with bone marrow fibrosis (MDS-F) is worse than the prognosis of MDS without fibrosis. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy; however, the indications and the procedures involved in HSCT remain unclear. We herein describe a 69-year-old Japanese man with MDS-F who received haploidentical HSCT and post-transplantation cyclophosphamide. Although the first HSCT resulted in secondary graft failure, the second HSCT using PTCy led to successful engraftment after early improvement in fibrosis. Since the incidence of graft failure is high in myelofibrosis patients, a secondary HSCT using PTCy may be successful if employed.

Toll-like receptor-2 modulates ventricular remodeling after myocardial infarction.

BACKGROUND: Toll-like receptors (TLRs) are members of the interleukin-1 receptor family and transduce similar signals as interleukin-1 receptor in response to exogenous pathogens. Recent studies have demonstrated that TLRs are activated by endogenous signals, such as heat shock proteins and oxidative stress, that may contribute to ventricular remodeling after myocardial infarction. In this study, we determined whether TLR-2 was involved in cardiac remodeling after myocardial infarction. METHODS AND RESULTS: Myocardial infarction was induced by surgical left anterior descending coronary artery ligation on wild-type (WT) mice and TLR-2-knockout (KO) mice. The survival rate was significantly higher in KO mice than in WT mice 4 weeks after myocardial infarction (65% versus 43%, P<0.03). Infarct size and degree of inflammatory cell infiltration in infarct area were similar between WT and KO mice. However, myocardial fibrosis in the noninfarct area of KO mice was much less than in WT mice (P<0.01) and was accompanied by reduced transforming growth factor-beta1 and collagen type 1 mRNA expressions (P<0.01 and P<0.05, respectively). Left ventricular dimensions at end diastole were smaller in KO mice than in WT mice at 1 week (P<0.05) and 4 weeks (P<0.01) after surgery. Furthermore, fractional shortening was higher (27.7+/-2.5% versus 21.2+/-2.6%, P<0.05, at 1 week, and 24.3+/-2.0% versus 16.6+/-2.5%, P<0.01, at 4 weeks) in KO mice compared with WT mice. CONCLUSIONS: These data suggest that TLR-2 plays an important role in ventricular remodeling after myocardial infarction.

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

BACKGROUND: Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. AIMS: PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. METHODOLOGY: A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. RESULTS: Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). CONCLUSIONS: In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began to be detected.

Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy.

Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN.

Immunohistochemical recognition of human follicular dendritic cells (FDCs) in routinely processed paraffin sections.

A number of monoclonal antibodies (MAbs) that recognize human follicular dendritic cells (FDCs) have been identified. Although some of them have already been applied individually in routine immunolabeling using formalin-fixed paraffin sections for diagnostic and experimental purposes, many antibodies are still employed only for immunolabeling using cryostat sections or particularly processed sections because they have been thought unsuitable for routine sections. A comprehensive examination re-evaluating their suitability in paraffin sections has not been reported. Accordingly, there is limited ability to examine the immunopathological contribution or diagnostic value of FDCs using routinely processed specimens or archived materials. In this study a broad panel of antibodies was systematically applied to the immunolabeling of paraffin sections of reactive tonsils or lymph nodes, in combination with advanced antigen retrieval (AR) techniques. Several antibodies, including Ki-M4p, X-11, 12B1, CNA.42, 1F8/BU32 (anti-CD21), BU38/1B12 (anti-CD23), Ber-MAC-DRC/To5 (anti-CD35), 1.4C3 (anti-CD106), NGFR5 (anti-nerve growth factor receptor p75), IIH6 (anti-CD55), 55K-2 (anti-fascin), and anti-S100 protein alpha-chain, were found to label FDCs in routine sections when combined with suitable AR techniques. Our results are easily adaptable for routine practice and provided useful suggestions concerning the immunopathological behavior and diversity of the particular cells.

Immunohistochemical diagnosis of a rare case of epithelioid malignant peripheral nerve sheath tumor with multiple metastases.

BACKGROUND: The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST) is a rare tumor with poor prognosis that sometimes involves the head and neck. The diagnosis is based principally on the histological examination, and it is generally very difficult to reach the correct diagnosis. CASE: An 84-year-old Japanese woman presented with a tumor mass of 2 week's duration in the right medial canthal region. OBSERVATIONS: Although the tumor was excised surgically, metastases occurred three times on her face and head, and the patient died of distant systemic multiple metastases. In the histopathological analysis, the tumor showed a composite pattern comprising spindle or polygonal cells arranged in irregular bands, and a population of larger epithelioid cells in solid sheets and nests. In the immunohistochemical analysis, the tumor cells were positive for S-100 protein, vimentin, and nerve growth factor receptor (NGFR), and negative for cytokeratin and HMB 45 (melanoma-associated antigen). These findings confirmed the diagnosis of MPNST. CONCLUSIONS: Epithelioid MPNST has complex histopathological findings and histopathological features similar to other epithelioid tumors, especially malignant melanoma. Immunohistochemical examination using NGFR and HMB-45 is important in the differential diagnosis.