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.

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.

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.

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.

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.

Synchronous Double Malignant Tumors Consisting of Stomach and Hodgkin's Lymphoma with Collision between Gastric Adenocarcinoma and Hodgkin's Lymphoma in the Stomach.

We report the rare case of a 72-year-old man with double cancers (gastric adenocarcinoma and Hodgkin's lymphoma) with collision between gastric adenocarcinoma and Hodgkin's lymphoma. Abdominal computed tomography showed increased wall thickness in the fundus region of the stomach and multiple lymph node swellings in the lesser curvature, periceliac and left cardial regions. Upper gastrointestinal endoscopy showed an ulcer approximately 5 cm in diameter with a malignant appearance in the fundus region of the stomach. On histopathologic examination, two completely different tumors were recognized in the stomach. One tumor was a poorly differentiated adenocarcinoma characterized by poorly developed tubular structures associated with prominent lymphoid infiltration of the stroma. The other tumor was found to have proliferated in the wall of the stomach, with diffuse granulomatous lesions and bordering the adenocarcinoma. Large atypical lymphoid cells with prominent nucleoli and enlarged mononuclei or multinuclei were seen in the latter tumor. Hodgkin's lymphoma was also found in the swollen lesser curvature lymph nodes. As a result, gastric adenocarcinoma and metastasis of Hodgkin's lymphoma were collided in the stomach. In conclusion, this case might be helpful in exploring the occurrence mechanism of tumor collision between lymphoma and carcinoma.

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.

Differential immunophenotypic analysis of dendritic cell tumours.

AIMS: The phenotypic and biological characteristics of dendritic cell (DC) tumours have not been fully elucidated. The aim of this study was to compare the immunophenotypic characteristics of DC-related markers and cell-cycle-associated markers among DC tumours and finally to utilise them for differential diagnosis of DC tumours. METHODS: Tissue sections from 28 patients with DC tumours were immunohistochemically examined using DC-related and cell-cycle-associated markers. RESULTS: The Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) samples were positive for S-100 protein, CD1a, Langerin, fascin, DEC-205 and DC-SIGN. Interdigitating dendritic cell sarcoma (IDCS) was positive for S-100 protein and fascin and negative for Langerin. In addition, two IDCS samples were positive for CD1a, DEC-205 and DC-SIGN. The labelling indices of Ki-67, cyclin A, cyclin B1 and acetylated histone H3 on the LCS and IDCS specimens were significantly higher than those on the LCH specimens. The expression of p53 was also significantly higher in the LCS specimens than in the LCH specimens. The numbers of infiltrating CD123(+) and FOXP3(+) cells were also significantly higher in the LCS samples than in the LCH and IDCS samples. Follicular dendritic cell sarcoma was distinguished from other DC tumours by the lack of DC-SIGN, Langerin and DCE-205. CONCLUSIONS: These results suggest that Langerin can be used to distinguish LCS from IDCS, and DC-SIGN and DEC-205 can be used to identify DC tumour cells. The frequency of cell-cycle-associated markers can be used for the differential diagnosis of malignant and benign DC tumours.

Clinicopathological significance of cell cycle regulatory factors and differentiation-related factors in pancreatic neoplasms.

OBJECTIVES: The aim of the present study was to compare the expression levels of the cyclins and the differentiation-related factors in pancreatic neoplasms. METHODS: The expression levels of cyclins A and B1, E1A-like inhibitor of differentiation 1 (EID-1), p300, 3'-5'-cyclic sdenosine monophosphate response element binding protein (CREB) binding protein (CBP), and acetylated histone H3 (AcH3) in ordinary ductal carcinoma (ODC) and intraductal papillary mucinous neoplasms (IPMNs) of the pancreas were investigated. RESULTS: More cells positive for cyclin A and EID-1 were present in the ODC than in the IPMNs. Cells positive for both cyclins and EID-1 were observed more frequently in invasive carcinoma derived from the IPMN than from the IP mucinous carcinoma. Multivariate regression analysis revealed that EID-1 and cyclin A overexpressions were independent factors associated with poor prognosis. Overall survival was significantly lower in ODC patients with overexpressions of cyclin A, EID-1, and AcH3 than in those without such overexpressions. There were significant differences in the survival curves between patients with ODC and invasive carcinoma derived from IPMN, regarding high frequency for cyclin A or B1. CONCLUSIONS: These results indicated that the expressions of cyclins A and B1, EID-1, and AcH3 may be correlated with a malignant potential in IPMNs. Invasive carcinoma derived from IPMN may be slow growing as compared with ODC.

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.

Distribution of myeloid dendritic cells and plasmacytoid dendritic cells in the synovial tissues of rheumatoid arthritis.

OBJECTIVE: To examine the precise tissue distribution of dendritic cells (DC) and indoleamine 2,3-dioxygenase (IDO)-expressing cells in synovial tissue and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues from 30 patients with RA and 7 with OA were immunohistochemically stained for DC markers. The examined areas were classified into 5 categories based on pathobiological staging and histopathological grading systems. Myeloid DC (mDC) and plasmacytoid DC (pDC) were isolated using positive and negative magnetic sorting systems, respectively, from SF samples (7 patients with RA and 4 with OA) and synovial tissues (3 RA, 4 OA). RESULTS: mDC were mainly observed in lymphoid aggregations. pDC were scattered around perivenular infiltration areas, and small and large lymphoid aggregations in RA. The mDC/pDC ratio increased significantly, with higher grading in RA SF tissues compared to OA synovial tissues (p<0.05). IDO-immunoreactivity was detected in pDC by serial sectioning and staining of RA synovial tissues. CONCLUSION: Our results indicate that mature mDC play a central role in the RA inflammatory process. Although there were fewer pDC than mDC, the presence of IDO-positive pDC suggests a possible tolerance mechanism in RA synovial tissues. However, it is probably modest due to the marked inflammation in RA, in which mDC are dominant.

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.

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.