Keiko Ishii

A dual staining method for identifying mucins of different gastric epithelial mucous cells

SummaryA dual staining method has been developed to identify two types of mucous secreting cells in the gastric mucosa of human and rat in one and the same tissue section. Sections were stained first using the galactose oxidase-cold thionin Schiff (GOCTS) procedure and then with paradoxical Concanavalin A staining (PCS). Surface mucous cell mucin stained blue with GOCTS, whereas gland mucous cell mucin stained brown with PCS. This method enabled us to differentiate these two types of mucins not only in gastric epithelial cell cytoplasm but also in the extracellular space. Sugar residues detected by GOCTS were explored by employing four species of lectins, which were peanut andAllomyrina dichotoma agglutinins for β-galactose andVicia villosa andWistaria floribunda agglutinins for β-N-acetylgalactosamine. The effect of oxidation with galactose oxidase was also examined on the affinities of reactive sites for these lectins. The results indicated that, in the human stomach, the sugar residues responsible for this reactivity were most likely β-N-acetylgalactosamine and β-galactose in specimens lacking secretion of blood group determinants and β-N-acetylgalactosamine in those showing the secretion. In the rat stomach, on the other hand, sugar residues responsible for GOCTS were not elucidated by these lectins.

A new view of the so-called adenoma malignum of the uterine cervix

Abstract Adenoma malignum of the uterine cervix (mucinous type of minimal deviation adenocarcinoma, mucinous MDA), is a unique neoplasm that is difficult to diagnose owing to the deceptively benign appearance of the tumour cells. The present study was undertaken to explore the phenotypic expression of this tumour compared with those of non-neoplastic cervical tissues and of cervical carcinomas of various types. Ten cases of mucinous MDA, 50 cases with non-neoplastic cervical tissues, 13 of cervical adenocarcinoma including the mucinous (endocervical or intestinal type) and endometrioid types, and 2 of mucoepidermoid carcinoma were examined by various histochemical staining methods, including those for gastric mucins, pepsinogen, lysozyme, chromogranin A and carcinoembryonic antigen. The results revealed that mucinous MDA characteristically exhibited gastric phenotypes. The presence of gastric metaplasia was also demonstrated in 9 cases of mucinous MDA and in 5 of the other cases examined. The 7 endocervical-type adenocarcinomas also included 4 that expressed gastric phenotypes, and 2 of the 3 intestinal-type adenocarcinomas showed the same properties focally. These results indicate the presence of a group of lesions expressing gastric phenotypes in the uterine cervix and suggest a close relationship between these lesions. Cervical adenocarcinomas expressing gastric phenotypes are probably derived from MDA.

MR of enchondroma and chondrosarcoma: rings and arcs of Gd-DTPA enhancement.

MR studies of five chondrosarcomas and three enchondromas were performed with intravenous Gd-DTPA administration. All tumors showed enhancement of scalloped margins and curvilinear septa (ring-and-arc pattern) on T1-weighted SE sequences with Gd-DTPA. On radiologic-pathologic correlation, the enhanced areas corresponded to fibrovascular bundles surrounding hyaline cartilage lobules. The rings and arcs of enhancement with Gd-DTPA on MR is a reflection of the lobulated growth pattern of cartilaginous tumors and therefore helpful in differential diagnosis of bone tumors.

Minimal deviation adenocarcinoma of the uterine cervix has abnormal expression of sex steroid receptors, CA125, and gastric mucin

SummaryTo provide clues to the histological differentiation between minimal deviation adenocarcinoma (MDA) of the uterine cervix and normal cervical glands, we analyzed the histochemical expression of ovarian steroid receptors [estrogen receptor (ER) and progesterone receptor (PR)], mucosubstances such as gastric mucin, CA125, and carcinoembryonic antigen (CEA) in normal cervical glands (10 cases) and MDA (seven cases). Mucin histochemistry showed that gastric mucin was focally demonstrated in all the cases of MDA but in none of the normal cervical glands. ER and PR were not expressed in MDA, whereas both receptors were invariably expressed in normal cervices. Expression of CA125 was significantly decreased in MDA, but was diffusely positive in normal endocervical glands. CEA was focally positive in all cases of MDA, but it was consistently negative in normal cervical glands. These results suggest that MDA lacks expression of the characteristic müllerian-type substances such as ER, PR, and CA125, and that a proportion of its cells contain gastric epithelial substances, comprising gastric mucin and CEA. In conclusion, loss of the expression of ER and PR, decreased expression of CA125, and staining for gastric mucin and CEA could be used for histologic discrimination of MDA from benign cervical glands.

Immunohistochemical study of hepatic angiomyolipoma

An immunohistochemical study was performed on nine hepatic anglomyolipomas (AML) found in eight patients. Histologically, the tumors were fundamentally composed of the three heterogeneous tissue components of blood vessels, smooth muscle cells (SMC), and fat cells, although the proportions and distributions were quite variable from tumor to tumor and from area to area in the same tumor. Additionally, cellular pleomorphism and atypia with occasional bizarre giant cells were found in the SMC component. This histologic feature might lead to a mistaken diagnosis of malignant neoplasm, and pathologists should therefore be aware of the broad histologic spectrum of hepatic AML. However, the Immunostalning patterns were basically the same in all nine tumors. All tumor components were negative for epithelial membrane antigen (EMA) and for cytokeratin. The spindle‐shaped SMC component of the tumor was occasionally positive for vimentin, desmin and alpha‐smooth muscle actin, whereas epithelioid SMC were negative for all three. Both the epithelioid and spindle‐shaped SMC were occasionally positive for S‐100 and neuron‐specific enolase. All types of SMC in the tumor, whether spindle, epithelioid, intermediate or pleomorphic SMC, were strongly positive for HMB‐45, a melanoma‐specific monoclonal antibody. Fat cells were occasionally positive for S‐100. Endothelial cells were positive for factor Vlll‐associated antigen. Among hepatic tumors HMB‐45 reactivity is, so far as we know, found exclusively in the SMC of AML, and the HMB‐45 reactivity of a hepatic tumor is thus clearly an important piece of information in the diagnosis of AML

Clinicopathological characteristics of atypical cystic duct (ACD) of the breast: Assessment of ACD as a precancerous lesion

To clarify the clinicopathological features of an atypical cystic duct (ACD) as defined by Tsuchiya’s criteria as a precancerous lesion of the breast, we used 200 whole mammary gland serial sections of breast cancer. Forty‐four (22%) of the 200 breast cancer patients had ACD breast lesions. The frequency of patients with ACD increased in premenopausal women (P= 0.001). There was no correlation between the ACD‐present group and the ACD‐absent group for immunohistochemical status of the estrogen receptor (ER), progesterone receptor (PgR), p53, or c‐erbB2; Ki‐67 labeling index of cancer tissues; size of tumor, or lymph node metastases. A number of ACD lesions displayed continuity to cancer lesions. In 500 serial sections of a paraffin‐embedded tissue of a ACD case at 3 μm intervals, an apparent transition from ACD into ductal carcinoma in situ was observed. Immunohistochemical analysis using α‐smooth muscle actin showed that myoepithelial cells of ACD stained strongly, and their nuclei and cytoplasm were thinning. In 16 of the 44 (36%) ACD‐present patients, carcinoma cells stained positive for p53. Within those 16 cases, 12 cases (75%) were positive for p53 in ACD lesions. There was a significant correlation between the expression of p53 protein in malignant cells and ACD (P= 0.001). All 44 ACD lesions had no staining of c‐erbB2, regardless of staining in malignant lesions. The mean Ki‐67 labeling index of ACD lesions was low (0.3%), suggesting that ACD had a low proliferative rate. We suggest that ACD is the precancerous breast lesion because of a histologic continuum between ACD and malignancy, and because of p53 protein expression in ACD.

Interdigitating cell sarcoma: a morphologic and immunologic study of lymph node lesions in four cases.

lnterdigitating cell sarcoma is an extremely rare tumor. Its presentation and histologic appearance has varied among the reported cases. In this study, the authors investigated four cases of the hematolymphoid malignancy arising within lymph nodes, which were considered to be of interdigitating cell origin. All patients presented in the 6th to 8th decade of life with peripheral lymphadenopathy, and had a relatively indolent clinical course, without bone marrow or skin involvement. Carcinomas were observed as a second neoplasm in two of four patients. Distinctive morphologic features are proliferation of histiocyte‐like cells with nuclear pleomorphism and occasionally multinucleated, paracortical distribution sparing of B‐cell regions, fibrosis, sinus infiltration, and a prominent eosinophi/plasma cell infiltrates. The combination of light microscopic, fine structural, and immu‐nohistochemical features suggested that these tumors derive from interdigitating cells: these tumor cells expressed CD68 (KP1), S‐100 protein and HLA‐DR, but lack CD21 (1F8), desmosomes and Birbeck granules. The diagnosis of interdigitating cell sarcoma should be considered on any pleo‐morphic tumor with the features described in this report.

Expression of Gastric Gland Mucous Cell-Type Mucin in Normal and Neoplastic Human Tissues:

Gastric gland mucous cells produce class III mucin, which is also found in Brunners glands and mucous glands along the pancreaticobiliary tract, and in metaplasia and adenocarcinomas differentiating towards gastric mucosa. Recently, we showed that class III mucin possesses GlcNAcα1→4Galβ→R, formed by α1,4-N-acetylglucosaminyltransferase (α4GnT). Examining the tissue-specific expression of mucin epitopes is useful to clarify cell-lineage differentiation and to identify the site of origin of metastatic carcinomas in histological specimens. Formalin-fixed, paraffin-embedded tissue sections from esophagus, stomach, colon, liver, pancreas, lung, kidney, prostate, breast, and salivary gland resected for carcinoma, as well as salivary gland adenoma, colon adenoma, and metastatic adenocarcinoma of lymph nodes from stomach, pancreas, colon, and breast, were immunostained for MUC6, α4GnT, and GlcNAcα1→4Galβ→R. These were all expressed in normal, metaplastic, and adenocarcinoma tissues of stomach, pancreas, and bile duct, and in pulmonary mucinous bronchioloalveolar carcinomas. Cells expressing α4GnT uniformly expressed GlcNAcα1→4Galβ→R. Only MUC6 was expressed in normal salivary glands, pancreas, seminal vesicles, renal tubules, and colon adenomas, and in normal tissue and adenocarcinomas of prostate and breast. No tissues showed immunoreactivity for α4GnT alone. Immunohistochemistry (IHC) profiles were similar for metastatic carcinomas and primary carcinoma tissues. The IHC profiles for MUC6, α4GnT, and GlcNAcα1→4Galβ→R may be diagnostically relevant.

MR of pulmonary hamartoma: pathologic correlation.

We describe the magnetic resonance (MR) appearance with pathologic correlation of six pulmonary hamartomas. All six tumors showed intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Four of the six tumors showed a lobulated appearance separated by septa on precontrast T1-weighted or T2-weighted images. Gadolinium-enhanced T1-weighted images showed marked enhancement of the septa that separated the tumors into less well enhanced lobules; this was seen in all six tumors. Comparison between MR images and pathologic specimens showed that the regions with less enhancement corresponded to core cartilaginous tissue and septa; areas of marked contrast enhancement corresponded to cleft-like branching mesenchymal connective tissue that dipped into the cartilaginous core. MR images correlated well with the surgically resected tumors.

Adenocarcinoma of the cervical oesophagus arising from ectopic gastric mucosa : the histochemical determination of its origin

A case of adenocarcinoma of the cervical oesophagus was examined by employing a battery of histochemical techniques and was demonstrated to arise from ectopic gastric mucosa. The patient was a 66-year-old Japanese male. Endoscopy revealed an ulcerated tumour on the right anterior wall of the cervical oesophagus, approximately 16 cm from the incisor teeth. Pathological examination of surgically removed specimens showed well-differentiated tubular adenocarcinoma. Ectopic gastric mucosa was found in the oesophageal mucosa adjoining the carcinoma. Histochemical stains for characterizing mucosubstances and immunostains for various antigens were used. In addition to this carcinoma, ectopic gastric mucosa in the oesophagus and normal oesophageal, cardiac, tracheal and bronchial mucosa were also examined. The results showed that the carcinoma contained mucins, which showed reactivities characteristic of the gastric surface mucous cell (galactose oxidase-cold thionin Schiff reactive) and gland mucous cell (paradoxical concanavalin A staining reactive). Ectopic gastric mucosa consistently contained these mucins, but other tissue sites lacked them.