Histogenetic considerations on mucinous cystomas of the ovary based on histochemical and immunohistochemical findings

Mucinous cystomas of the ovary, according to a new proposed classification (I.A.P., Dublin 1988), are classified in three types: endocervical, intestinal and mixed. Their histogenesis is still controversial, thus requiring further investigations. There are two main theories on this matter: a teratomatous theory based on the assumption that the mucinous cystoma is allegedly a teratoma having a monophyletic development where only the endodermal gastrointestinal component remains. The second theory, currently the most widely accepted one, maintains that mucinous cystomas derive from Muller duct residues or, more generally, from introflections of the coelomic epithelial lining through a Muller-type metaplastic process. Some authors also accept both theories. A group of 117 mucinous cystomas were investigated by histochemical methods (PB/KOH/PAS; PAT/KOH/Bh/PAS), to demonstrate the presence of O-acetylated sialomucin variants in goblet cells of intestinal type component. Endocervical type mucinous cystomas have always presented as PB/KOH/PAS negative, whereas mixed type mucinous cystomas presented as positive according to the following percentage: benign forms, 31%; borderline, 67%; malignant, 50%. These data should confirm the hypothesis that intestinal type cystomas may derive from the surface coelomic epithelium of the ovary, through a gastrointestinal metaplastic process. This hypothesis is further supported by the data obtained from the observation on two cases of intestinal metaplasia of endocervical glands, kindly supplied by Dr. Trowell. In one of them, a weak O-acetylated sialomucin secretion was identified, in addition to the presence of argentaffin cells. Furthermore, out of 38 adenocarcinomas of the endometrium and 15 adenocarcinomas of the endocervix, one case of endocervical adenocarcinoma was found, characterized by a mucous secretion rich in O-acetylated sialomucins. Moreover, immunohistochemically, by means of anti-chromogranin A monoclonal antibodies, endocrine cells were found in benign, borderline and malignant mucinous cystomas of mixed type. These data do not seem to confirm the assumed correlation between neuroendocrine cell presence and biologic behaviour of the neoplasm nor do they clarify tumor histogenesis. Another immunohistochemical study with BD5 monoclonal antibody demonstrated that this marker was present in the intestinal type epithelium of mixed mucinous cystomas. The histogenetic teratomatous hypothesis of ovarian mucinous cystomas was confirmed by reviewing 100 ovarian teratomas, in which O-acetylated sialomucins were found in the epithelial component of one mucinous carcinoid and in the intestinal type epithelium of 9 mature cystic teratomas.(ABSTRACT TRUNCATED AT 400 WORDS)     

Retrospective histochemical study of mucosubstances in adenocarcinomas of the gastrointestinal tract

Use of the PATS/KOH/PAS and PB/KOH/PAS techniques and the diamine method (Spicer 1965) together with the demonstration of metachromasia with toluidine blue pH 3.0, for the study of carbohydrates in a retrospective study of gastric and colorectal adenocarcinomas, disclosed an increase in the sulphate content and the absence of O-acylated sialomucins in the majority of gastric adenocarcinomas. In the colorectal tumours there is no change in the degree of sulphation normally present in this area, but the degree of acylation of the sialic acid in adenocarcinoma is very different to that of normal mucosa and appears related to the degree of differentiation of the tumour. The mucosa adjacent to tumours from both areas were also studied, as well as gastric intestinal metaplasia.     

A study of vesical adenocarcinoma, intestinal metaplasia and related lesions using mucin histochemistry

Biopsy and autopsy material from the urinary bladder was studied using PAS and PAS-D techniques to identify glycogen and neutral mucins, the alcian blue/high iron diamine method to distinguish sialo- and sulphamucins and the PB/KOH/PAS technique to localize O-acylated sialomucins. All of 10 examples of normal urothelium and both of two cases of transitional carcinoma in situ contained glycogen, but no mucin. Other lesions displayed one of two patterns of mucin production: the extracellular mucin seen focally in 17 cases of cystitis cystica consisted of sialo- and/or neutral mucins only, a pattern also displayed by mucins produced in 10 of 13 examples of transitional cell carcinomas and by three of nine tumours purely or in part adenocarcinomas. The intracellular mucins expressed in five of the 17 cases of cystitis glandularis and in all of eight cases of frank intestinal metaplasia with goblet cells displayed a colonic phenotype, with production of O-acylated sialomucins. A similar profile was expressed by six adenocarcinomas and this included tumours likely to be of vesical and also of urachal origin. It is concluded that identification of O-acylated mucins cannot distinguish between primary bladder tumours and metastases from a colonic primary, or between carcinomas of vesical and urachal origin.     

正常胃肠道上皮粘液性质及其显示方法

应用组织化学方法包括PAS,AB/PAS,HID/AB,OR/AB,PAPS,mPAS,PB/KOH/PAS,PAT/KOH/PAS,PATB/KOH/PAS观察正常胃肠道粘膜分泌粘液的成分.对各种组织化学方法进行了比较,并对国内尚无报告的新方法进行了介绍.在正常胃粘膜表面上皮及胃窦腺体以分泌中性粘液为主.小肠主要分泌氮乙酰化唾液酸粘液,大肠上皮分泌以硫酸粘液及氧乙酰化唾液酸粘液为主.     

Mucin histochemistry of cystitis glandularis and primary adenocarcinoma of the urinary bladder

We describe the histochemical properties of mucin in three cases of cystitis glandularis affecting the urinary bladder. Of particular importance is the positive staining reaction that was obtained with the periodate borohydride/potassium hydroxide/PAS (PB/KOH/PAS) technique, indicating the presence of O-acetylated sialic acids. This reaction has been regarded as unique to the epithelial mucins in the normal terminal ileum and large intestine. Therefore, cystitis glandularis represents a true mucous metaplasia of large intestinal type. A case of primary adenovillous carcinoma of the bladder associated with cystitis glandularis also produced O-acetylated sialomucin, whereas a primary adenocarcinoma of urachal origin did not. The demonstration of O-acetylated sialic acid producing glandular epithelium in the bladder cannot be assumed to represent a metastasis from a colorectal cancer. The PB/KOH/PAS staining technique may provide a means of distinguishing between primary adenovillous and primary urachal carcinoma of the bladder.     

HISTOCHEMICAL DEMONSTRATION OF COLONIC TYPE MUCIN IN GLANDULAR METAPLASIA and ADENOCARCINOMA OF THE HUMAN URINARY BLADDER

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.     

Histochemical demonstration of colonic type mucin in glandular metaplasia and adenocarcinoma of the human urinary bladder

Mucin in normal, metaplastic and neoplastic tissue specimens of the human urinary bladder was examined histochemically by the periodic acid-borohydride/potassium hydroxide/periodic acid-Schiff (PB/KOH/PAS) reaction and paradoxical concanavalin A (Con A) staining, both of which have been reported to detect mucins that are specific for the lower gastrointestinal tract. Normal mucosa, Brunn's nest, squamous metaplasia, transitional cell carcinoma, and squamous cell carcinoma produced only small amount of mucin and were negative for both PB/KOH/PAS and labile class III by Con A staining. However, several sections of mucin-producing metaplastic bladder lesions and many samples of adenocarcinoma arising from vesical mucosa and urachus contained PB/KOH/PAS-positive and/or labile class III mucin. Thus the colonic type mucin appeared in some materials of both benign and malignant mucin-producing lesions of the urinary bladder. The findings would be related to the embryogenesis of this organ.     

Primary adenocarcinomas of the human urinary bladder: Histochemical,immunological and ultrastructural studies

Summary Neoplastic and non-neoplastic tissue specimens from ten patients with primary adenocarcinoma of the urinary bladder were examined. Most of these tumors were associated with either foci of transitional cell carcinoma and/or with glandular metaplasia of the bladder epithelium. The mucin produced by the neoplastic cells was PAS, alcian blue, mucicarmine, PB/KOH/PAS, and RPB/KOH/PAS-positive. ABH isoantigens of these tumors were not always deleted. Ultrastructurally, the neoplastic cells resembled goblet cells. Their plasma membrane had numerous microvilli with prominent glycocalyx. Proliferation and attenuation of tight junctions were noted. The gap junctions were few and small. Two types of desmosomes were found. The ultrastructural features of the neoplastic cells were attributed in part to the malignant transformation and in part to the direction of their differentiation. We have not observed any distinctive morphologic, histochemical, immunologic or ultrastructural features that might be diagnostic for these adenocarcinomas.This study was supported by the Institute of International Education, New York; the Charlton Fund, Tufts University School of Medicine; and Grants#CA-15776 and CA 23776 from the National Cancer Institute     

PAS-positive lymphatic cells in angioimmunoblastic lymphadenopathy

Summary Cytological preparations have been investigated with the PAS-reaction in 8 cases of angioimmunoblastic lymphadenopathy, 7 of which were malignant, including 2 cases of plasmoblastic sarcoma. The two sarcoma cases showed intensely PAS-positive tumor cells similar to those known from acute leukemias and malignant lymphomas. Two cases of malignant angioimmunoblastic lymphadenopathy disclosed very many, two more such cases only occasionally positive cells. One malignant case only was completely negative. Some positive cells were found in the case that appeared benign. The PAS reaction is recommended as a diagnostic aid in angioimmunoblastic lymphadenopathy.     

Significance of mucin stain in differentiating benign and malignant lesions of prostate

In an attempt to assess the significance of mucin stains in benign and malignant lesions of prostate, 200 prostatic biopsies in the department of Pathology, Pt. B.D. Sharma PGIMS, Rohtak were studied. All the biopsies were subjected to PAS and alcian blue staining along with H&E stain. Neutral mucin (PAS positive) was more frequently observed in benign prostatic lesions (93.3%) as compared to carcinoma (36%) while acid mucin (AB positive) was found more in carcinoma prostate (68%) as compared to benign prostatic lesions (16%). The positivity for acid mucin was more in well differentiating tumour decreasing significantly in high grade malignancies. With both types of mucin, luminal positivity was slightly more as compared to cytoplasmic positivity.     

A new histochemical technique of use in the interpretation and diagnosis of adenocarcinoma and villous lesions in the large intestine.

The periodic acid-thionin Schiff/potassium hydroxide/periodic acid-Schiff (PAT/KOH/PAS) procedure has been used to investigate the histochemical staining characteristics of the mucins found in adenocarcinoma and villous lesions of the large intestine. The 46 blocks examined represented 58 lesions from 37 patients, all of whom had had resections for carcinoma of the colon. tin sharp contrast to normal colon, none of the adenocarcinomas stained red with the PAT/KOH/PAS. With two exceptions the poorly and moderately differentiated adenocarcinomas stained blue, whereas of the well differentiated lesions half were blue and half purple. The malignant villous lesions demonstrated the same trends, although a larger percentage were purple. None of the benign lesions stained blue. It is suggested that malignancy in the colon is accompanied by an increase in blue staining in the PAT/KOH/PAS technique and that such staining may be of value in the interpretation of highly atypical adenoma where it might identify the onset of malignancy. This change in staining indicates a distinct alteration in the chemistry of the mucins which we interpret as a reduction in the degree of side chain O-acylation of their constituent sialic acids.     

CD133 marks for colorectal adenocarcinoma

CD133, a marker which has been advocated to mark colorectal carcinoma "stem or tumour initiating cells" is amongst the frequently studied markers in colorectal cancer. A study was conducted at the Department of Pathology, University of Malaya Medical Centre to determine the expression of CD133 in 56 archived, formalin-fixed, paraffin-embedded colorectal adenocarcinoma in comparison with adjacent benign colorectal epithelium by immunohistochemical staining for CD133 expression. CD133 immunopositivity was determined as staining at the glandular luminal surface or in the intraluminal debris. Expression was semiquantitated for (1) proportion of CD133 immunopositivity in the malignant or adjacent benign colorectal epithelium and (2) intensity of staining. The final score of CD133 immunopositivity was arbitrarily taken as proportion of CD133 immunopositivity multiplied by intensity of staining in both the malignant and adjacent benign colorectal epithelium. CD133 expression was observed in significantly increased frequency in 49 (87.5%) colorectal adenocarcinoma compared with 15 (26.8%) of the adjacent benign colorectal epithelium (p<0.05). In terms of immunopositivity score (proportion of CD133 immunopositivity multiplied by intensity of staining), colorectal adenocarcinoma had a mean arbitrary score of 8.5 which was significantly higher than the mean immunopositivity score of 0.5 of the adjacent benign colorectal epithelium (p<0.05). In addition, the maximum immunopositivity score for the adjacent benign colorectal epithelium was 4, while 38 (67.9%) of colorectal adenocarcinoma had scores >4. This study shows that CD133 is able to mark colorectal adenocarcinoma but it is still unclear at this juncture whether CD133 is indeed a marker for colorectal adenocarcinoma "stem cells".     

MUCOUS SUBSTANCE and ENZYME HISTOCHEMISTRY OF NON-NEOPLASTIC and NEOPLASTIC GASTRIC EPITHELIUM IN MAN

On a consecutive series of 100 cases of gastric carcinoma, htstochemi-cal investigation of mucous material and 7 kinds of enzymes, including dehydrogenases, phosphatases, and lysosomal enzymes was performed. Mucous membrane of twenty stomachs resected for ulcer served as control. Histologically, thirty of the carcinomas were well-differentiated, 47 moderately differentiated, and 23 undifferentiated adenocarcinomas. A combination of histochemical reaction of two enzymes, alkaline phosphatase and aminopeptidase was found to be characteristic for the intestinal epithelium, both benign and malignant. Thus, carcinomas consisting of malignant epithelium fulfilling these characteristics could be classified as of intestinal epithelial type, and the others as of non-intestinal epithelial type. Correlation of tubular structural differentiation of carcinoma and this histochemical differentiation was examined: 14 of 30 (46.7%) morphologically well differentiated, 20 of 47 (42.6%) moderately differentiated, and 10 of 23 (43.5%) undifferentiated adenocarcinomas were classified histochemically in the intestinal epithelial type. There is, apparently, no direct correlation between the enzymatic characteristics and the morphological tubular "differentiation". It is apparent that the diffuse type of LAUREN¹⁶ is not "non-intestinal".     

Intracellular J chains in lymphoproliferative diseases

Summary The presence of J or joining chains has been studied in formolparaffin tissue sections from various lymphoproliferative diseases. The percentages of J chain positivity in 56 cases of multiple myeloma, in 41 of immunocytic malignant lymphoma and 35 of immunoblastic malignant lymphoma were 58.9, 70.7 and 37.1%, respectively. The ratio of chain types of the monotypic Ig-s was the lowest in multiple myeloma, intermediate in immunocytic and highest in immunoblastic malignant lymphoma (ml). In 8 cases (one local immature plasmocytoma, one non-secretory multiple myeloma, one immunocytic, 4 immunoblastic and one centroblastic malignant lymphoma), only J chains were present in the tumour cells - J chain disease. A significant difference in survival of J chain positive (26.8 months) and negative (17.7 months) multiple myeloma cases was observed. Myeloma kidney lesions were slightly more frequent in J chain negative cases. In lymphoproliferative disease J chain seems to be associated with early events of Ig synthesis. On the other hand, in two cases with biclonal Ig-s, the IgM positive immunoblastic ml cells and inclusions and the IgA positive multiple myeloma cells and inclusions were J chain positive. The IgG positive cells in both tumours and the IgG positive inclusions in the immunoblastic tumour were negative for J chains.     

Light and electron microscopy of parathyroid carcinoma

Summary The morphology of three cases of parathyroid carcinoma is described, including the electron microscope findings in two of these cases. The clinical and morphologic points for the tentative diagnosis of parathyroid carcinoma are discussed. The malignancy of a parathyroid tumour is proved by lymphogenic or hematogenic metastases, by histological evidence of tumour infiltration into the surrounding tissues (including macroscopic adherence and sometimes vocal cord paralysis), and by cytologic evidence of mitoses. Nuclear atypism is often present but is neither a necessary nor an adequate proof of malignancy, because it is also seen in benign adenomas and in hyperplastic parathyroids. The ultrastructure of the carcinoma cells was also characterized by nuclear atypism and mitoses. In one carcinoma, the contents of cytoplasmic organelles varied in different cells, indicating various endocrine activity of the tumour cells. In another parathyroid carcinoma with low endocrine activity, copious cytoplasmic organelles and many secretory granules were found. There seem to be three possible causes of non-functioning parathyroid carcinomas: 1. lack of hormone synthesis, 2. impairment of cellular hormone secretion, 3. synthesis of a pathologic protein with defective endocrine activity.Supported by DFG, Sonderforschungsbereich 34 Endokrinologie.     

Immunohistochemical localization of HCG and its subunits in testicular germ cell tumours

Summary Native hCG and its and subunits have been localized by immunocytochemistry in 45 testicular germ cell tumours of the testis.Positivity was found for the three molecules in areas with trophoblastic differentiation or in syncytial-like giant cells present in some seminomas. Isolated positivity of hCG was demonstrated in isolated cells usually found in areas of entodermal differentiation of immature malignant teratomas, and probably of neuro-endocrine function.This finding points to genomic derepression in tumour cells and probably also indicates a variability in subunit synthesis and a defect in subunit recombination.Supported by GRANT n^o 3.4530.81 of FRSM and by the FONDS CANCEROLOGIQUE of C.G.E.R.     

A histochemical comparison of the O-acylated sialic acids of the epithelial mucins in ulcerative colitis, Crohn''s disease, and normal controls.

Two histochemical techniques, the PAT/KOH/PAS and the PBT/KOH/PAS, were used to investigate the side chain O-acyl substitution patterns of the sialic acids of the colonic epithelial mucins in cases of ulcerative colitis and Crohn's disease. In both diseases there was, as compared to normal, a reduction in the proportion of sialic acids O-acylated at C7C8, the reduction being greater in ulcerative colitis. Further, there appeared to be an association between the severity of the disease and the reduction in the staining of O-acylated sialic acids. This relationship was more marked in ulcerative colitis. In some cases of both diseases there was evidence for epithelial mucins containing predominantly C7-substituted sialic acids. This study has confirmed our previous conclusion that, in Crohn's disease of the terminal ileum, the disease is associated with an increase in the proportion of sialic acids bearing side chain substituents.     

Effects of PAF and PAF antagonists on the shape of venous endothelial cellsin vitro

Three platelet-activating factor (PAF) antagonists were tested for their ability to prevent or reduce PAF-induced shape changes of large vein endothelial cellsin vitro. BN52021 had a significant protective action at concentrations of 1 M and 0.1 M, but at 100 M had a damaging effect of its own. CV3988 (0.1 M and 1 M) and L652, 731 (20 M) did not reduce the responses to PAF, and at higher concentrations (CV3988 10 M and 100 M, L652, 731 100 M) both compounds alone caused significant changes of shape. BN52021 (0.1 M) was also effective against leukotriene (LT) C₄, at 1 M against bradykinin and LTE₄, and at 10 M against LTD₄ and the calcium ionophore A23187. BN52021 (10 M) was ineffective against shape changes induced by histamine, prostaglandin (PG) E₂ and lysophosphatidylcholine (LPC). Neither indomethacin (100 M) nor verapamil (20 M) altered the response to PAF.Using electron spin resonance (ESR) spectrometry it was shown that the damaging effects of LPC and CV3988 may be due partly to their detergent properties. It is suggested that the mechanism by which PAF alters the shape of large vein endothelial cells is primarily receptor mediated.