Luminal Mucin Research Articles

Papillary (chromophil) renal cell carcinoma with mutinous secretion

We investigated the presence of mucin in a series of 20 papillary renal cell carcinomas. Acid mucin was present in three cases (15%), in which basophilic mucin secretion was evident with hematoxylin-eosin. This secretion reacted positively with Mayer's mucicarmine, Alcian blue and high-iron diamine, but was negative for PAS in all the cases, indicating the presence of sulphomucins. We describe two different types of mucin secretion: luminal and intracytoplasmic. The secretion was abundant, diffuse or extensive, luminal in two cases and intracellular in numerous scattered tumor cells in one case. All tumors were < 3 cm in diameter (low grade, stage I). In the three mucin-secreting papillary tumors mentioned above, the immunohistochemical and lectin studies indicate both a proximal and a distal tubular staining pattern. Mucinous secretion in these tumors can be ascribed either to modulation or direct metaplasia of the tumor epithelium. Mucin production, despite its low frequency, can be considered an additional feature of papillary renal cell carcinoma. Thus, the presence of luminal or intracytoplasmic mucin deposition does not exclude papillary renal cell carcinoma from the differential diagnosis in cases of intra- or extrarenal carcinomas.

Altered mucin expression is a field change that accompanies mucinous (colloid) breast carcinoma histogenesis

Mucinous carcinomas of the breast, so-called colloid carcinomas, exhibit better prognoses than their nonmucinous breast counterparts. This biological difference exhibited by mucinous breast carcinomas prompted us to examine the relationship of mucin expression to colloid carcinoma histogenesis. We studied 50 colloid carcinomas, 50 noncolioid cancers, and 50 normal breasts by hematoxylin-eosin (H&E) and Alcian blue staining, mucin immunohistochemistry, in situ hybridization with a battery of MUC riboprobes, and ancillary digital image analysis. We observed luminal mucin in normal ducts in 80% of colloid carcinomas compared with 10% of noncolloid carcinomas and 6% of normal breasts ( P < .01). In the cases of colloid carcinoma that showed mucin-filled ducts, luminal mucin was observed in 40% of the normal ducts and acini, 40% to 75% of the ducts involved by hyperplasia, atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), respectively, and in 50% of the co-incidental areas of cysts (mucoceles), adenosis, fibroadenoma, and intraductal papilloma ( P < .01). Immunohistochemistry showed that colloid carcinomas showed strong MUC2 cytoplasmic immunoreactivity and decreased MUC1 immunoreactivity compared with noncolloid carcinomas. In situ hybridization studies indicated fivefold increased MUC2 signals and twofold increased MUC5 signals within adjacent and remote normal epithelium in only the colloid carcinoma cases ( P < .01; P < .05). In these cases of colloid carcinoma, these increased MUC2 and MUC5 signals were also observed in areas of hyperplasia, ADH, DCIS, and invasive carcinoma. In contrast, the noncolloid carcinomas showed fivefold increased MUC1 signals but no increases in MUC2 or MUC5. In mixed colloid/noncolloid carcinomas, the colloid areas had identical mucin expression patterns as the pure colloid carcinomas, but there was a loss of MUC2 and MUC5 expression and a gain of MUC1 expression in the noncolloid areas that was therefore identical to the pattern observed in pure noncolloid carcinoma. In this study, we conclude that the altered expression of mucin so characteristic of colloid carcinoma is also a field change present in adjacent and remote normal breast epithelium.

Diagnosis of “Suspicious for Malignancy” in Prostate Biopsies: Predictive Value for Cancer

Objectives. Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for but not diagnostic of malignancy. The predictive value of ASAP for cancer has not been studied in a large series. Methods. To determine the reproducibility and clinical significance of ASAP in a large urologic reference laboratory, we retrospectively studied 295 patients with ASAP diagnosed from 1991 to 1995. Each patient had at least one follow-up biopsy. Mean patient age was 68.0 years (range 40 to 89). Numerous clinical and histologic features were assessed to determine their predictive value for malignancy on subsequent biopsy. Results. Adenocarcinoma was identified on follow-up biopsy in 125 patients (42%), with a median follow-up of 5.7 months (range 0.1 to 43). Gleason score varied from 4 to 9 (mean 6.2). Cumulative detection of 125 cancers was 90% after second biopsy and 99% after third biopsy. Serum prostate-specific antigen, digital rectal examination result, and patient age were not predictive of cancer on follow-up biopsy. Likewise, the number of biopsy cores and histologic findings including number of acini per focus of ASAP, number of foci of ASAP, degree of nuclear and nucleolar enlargement, and presence of luminal pink granular secretions, mucin, or crystalloids were not predictive of cancer. Stratifying our level of suspicion into three categories (favor benign, uncertain, and favor carcinoma) did not differentially predict subsequent cancer (44%, 44%, and 41% of patients, respectively; P = 0.86) nor the percentage of tissue involved by cancer. No clinical or pathologic feature affected the likelihood of subsequent cancer. In 39% of patients, cancer was only contralateral to or in a different sextant site from the initial ASAP site. Conclusions. The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. Sampling should include multiple sites in the prostate.

Oral human spasmolytic polypeptide protects against aspirin-induced gastric injury in rats.

Spasmolytic polypeptide (SP) is a member of the trefoil peptide family; gut peptides that participate in the protection and repair of the gastric mucosa. Previous studies have failed to agree on the mode of action of human SP (hSP). We investigated the effect of orally administered human SP on the protection and repair of rat gastric mucosa in an established in vivo model of damage induced by the non-steroidal anti-inflammatory drug aspirin (ASA). The integrity of the gastric mucosa was quantified in four ways: the temporal change in transmucosal potential difference (PD), area of macroscopic damage by planimetry, relative area of microscopic damage by histological morphometry, and the number of deep erosions per centimetre of mucosa sectioned. Human SP (200 micromol/L) administered orally before, or in combination with ASA significantly reduced the fall in PD, the area of microscopic damage, and the number of deep erosions (P < 0.05). The area of macroscopic damage was significantly reduced only in rats where hSP (200 micromol/L) was given in conjunction with ASA (P < 0.05). Human spasmolytic polypeptide (70 or 200 micromol/L) administered after ASA failed to hasten the re-establishment of PD or stimulate the repair of the gastric mucosa in the 90 min following injury (P > 0.05, compared with ASA alone). We conclude that hSP prevents gastric mucosal damage by its topical actions, probably by a rapid interaction with luminal mucins or epithelial cells, but fails to stimulate early restitution in the injured gastric mucosa.

Atypical small acinar proliferation suspicious for malignancy in prostate needle biopsies: clinical significance in 33 cases.

Prostate needle biopsies occasionally contain an atypical small acinar proliferation (ASAP) that is suspicious for, but not diagnostic of, adenocarcinoma. The histologic features and clinical significance of this finding are unexplored. We evaluated 33 cases of ASAP with at least one follow-up needle biopsy seen at Mayo Clinic from 1993 to 1996. Numerous histologic and clinical features were assessed to determine their predictive value for adenocarcinoma on subsequent biopsy. Mean patient age was 61.6 years (range 45-72). Adenocarcinoma was identified on follow-up biopsy in 15 of 33 patients (45%), with a median follow-up of 9 months (range 1-27). Gleason score varied from 4 to 7 (mean 5.9). Two patients (6%) had subsequent diagnoses of ASAP after one and three repeat biopsies. Digital rectal examination, serum prostate-specific antigen, and a variety of histologic findings were not predictive of cancer on follow-up biopsy. These histologic findings included number of biopsy cores (mean 5.5), number of acini per focus of ASAP (mean 7.9), number of foci (mean one), variation in acinar size, nuclear enlargement (none, 12% of cases; mild, 45%; moderate, 33%; severe, 10%), nucleolar enlargement (none, 27%; mild, 46%; moderate, 27%), luminal mucin (39%), crystalloids (6%), focal chronic inflammation (64%), adjacent atrophy (100%), and adjacent high-grade prostatic intraepithelial neoplasia (PIN) (42%). Stratification of suspicion in cases of ASAP without PIN into three categories ("favor benign, uncertain, and favor carcinoma") was somewhat predictive of subsequent cancer (20%, 25%, and 60% of cases with subsequent cancer, respectively), but the results were not significant. The high predictive value of ASAP for subsequent adenocarcinoma warrants repeat biopsy. No single clinical or pathologic feature appeared to increase the likelihood of subsequent cancer.

Effects of dietary fibers on gastrointestinal mucin in rats

Gastrointestinal mucin is believed to contribute to the intestinal diffusion barrier for nutrients. This study quantitated the effects of feeding three dietary fibers on gastrointestinal mucin production. Male Wistar rats (150–175 g) were fed, ad libitum , a diet containing 10 or 20% cellulose, psyllium, or rice bran or a control diet containing no fiber. After 4 weeks, the stomachs, small intestines, and colons were removed, and surface luminal mucin and tissue mucin were collected. Specimens were homogenized, the homogenates were centrifuged, and the supernatants were assayed for mucin by an enzyme-linked immunosorbent assay (ELISA) technique. The results of the dietary fiber feeding showed that levels of luminal and total (luminal plus tissue) gastric mucin were significantly higher in rats fed 20% psyllium than in rats fed the control diet. There were no significant differences in the levels of small intestinal mucin among groups. Colonic luminal and total mucin levels, however, were significantly increased in rats fed 10% psyllium compared with those of rats fed the control diet. The increase in colonic mucin levels was later confirmed by periodic acid Schiff (PAS) staining. It was observed that large amounts of mucus may have been lost in the feces of rats fed a diet containing 20% psyllium, and smaller amounts in the feces of those fed 10% psyllium. Reduced absorption of cholesterol and fatty acid was found previously in psyllium-fed rats. Thus, increases in gastric and colonic mucin levels caused by psyllium treatment may protect these organs as well as alter nutrient absorption.

Primary mucoepidermoid carcinoma of the thyroid gland: A report of six cases and a review of the literature of a follicular epithelial-derived tumor

Primary mucoepidermoid carcinomas of the thyroid gland are uncommon tumors of low-grade malignant potential. We report six cases of thyroid mucoepidermoid carcinoma, four occurred in women and two in men with an age range of 29 to 57 (median, 46 years). The clinical presentation was that of a painless mass. Radiographic studies showed a single, solid, “cold” nodule in either the right or left lobe, or isolated to the isthmus. There was no history of a mucoepidermoid carcinoma developing in more typical locations (eg, salivary gland) in any of the patients. Histologically, the tumors were characterized by an intimate admixture of squamoid/epidermoid cells and mucocytes. The tumors were delineated but not encapsulated with prominent cyst formation and a variable amount of associated fibrosis. The squamoid component showed horny pearl formation, individual cell keratinization and/or the presence of intercellular bridges. Intracytoplasmic and luminal epithelial mucin was observed in all cases. In three of the cases a prominent eosinophilic cellular infiltrate was intimately identified within the neoplastic proliferation. One other case was noteworthy for the presence of ciliated epithelium. In all of the cases the uninvolved thyroid tissue showed the presence of lymphocytic thyroiditis. Rare foci of squamous metaplasia were observed in two of the cases. A microscopic focus of thyroid papillary carcinoma was observed adjacent to the mucoepidermoid carcinoma in one case. Immunohistochemical evaluation of the mucoepidermoid carcinoma showed the following antigenic profile: cytokeratin (five of five), CAM 5.2 (four of four), thyroglobulin (five of six), calcitonin (none of six), chromogranin (none of six), polyclonal carcinoembryonic antigen (four of four), and monoclonal carcinoembryonic antigen (none of five). Surgical excision was the treatment of choice. All of the patients reported are alive without disease (recurrence or metastasis) over periods ranging from 1 to 15 years. Based on our findings, we believe that these tumors are of low-grade malignant potential and originate from thyroid follicular epithelial cells rather than from solid cell nests of the ultimobranchial body.

Neural mediation of cholera toxin-induced mucin secretion in the rat small intestine

We examined the role of enteric nerves in cholera toxin (CT)-induced mucin secretion in proximal and distal regions of rat small intestine. Stimulation of intestinal loops with 120 micrograms (1.5 mumol) CT using an in vitro open-loop model resulted in an approximately four-fold increase in luminal mucin content over unstimulated controls in both regions of the gut. Prior treatment of loops with tetrodotoxin had no effect on the amount of mucin released in response to CT. However, permanent destruction of primary sensory afferent nerves by neonatal treatment of rats with capsaicin reduced the mucin response to CT to baseline levels in both regions. In normal animals, atropine resulted in approximately 40% inhibition of mucin secretion in both the proximal and distal small intestine. The atropine-sensitive secretory response appears to be a component of the capsaicin-sensitive response. These results suggest that choleraic mucin secretion is mediated primarily by a capsaicin-sensitive neurogenic pathway involving local activation of sensory nerves, which may then elicit mucin secretion through interaction with cholinergic nerves.

Simple mucin-type Tn and sialosyl-Tn carbohydrate antigens in salivary gland carcinomas

Neoplastic transformation is associated frequently with changes in the glycosylation process. Simple mucin-type glycosylation in cancer cells has been found to be characterized by incomplete synthesis with precursor accumulation, leading to the exposure of the structures Tn and sialosyl-Tn, which are normally cryptic in human cells and secretions, including saliva and salivary glands. Paraffin sections from 50 salivary gland carcinomas of different histologic types were investigated with immunohistologic studies and a panel of monoclonal antibodies with well-defined specificity for Tn and sialosyl-Tn. Tn and sialosyl-Tn antigens were expressed in the cytoplasm of glandular differentiated cells; in the luminal membranes and mucinous content of the glandular differentiated areas in almost all mucoepidermoid carcinomas and adenocarcinomas; and in carcinoma in pleomorphic adenoma, when the malignant component was an adenocarcinoma. In contrast, acinic cell carcinomas and adenoid cystic carcinomas expressed only minimal amounts of Tn and sialosyl-Tn, and the staining was seen only in relation to the luminal membrane and mucin of a few glandular structures. Mucin-type Tn and sialosyl-Tn may be regarded as markers of a glandular differentiation pattern in salivary gland carcinomas. The cellular location of the antigen-antibody complex indicates that they are synthesized and secreted from the tumor cells into saliva or serum.

Sclerosing Adenosis of the Prostate Gland

Eleven cases of sclerosing adenosis of the prostate gland, a recently reported uncommon pseudoneoplastic lesion with characteristic histological, histochemical, and immunohistochemical features, are described. The well-circumscribed cellular lesions were composed of variably sized and shaped, often compressed, glands and small clusters of epithelial cells embedded in a cellular, often myxoid stroma. Mild cytologic atypia was occasionally present, and one case had moderate cytologic atypia. A distinct basement membrane often surrounded the glands and clusters. Luminal acid mucin was typically present. Keratin-positive basal cells were present in the glands and as spindle cells in the stroma. The basal cells were also immunoreactive for S-100 and muscle-specific actin, suggesting myoepithelial differentiation. Clinical follow-up has shown no evidence of prostatic carcinoma. The available evidence suggests that sclerosing adenosis of the prostate gland is a benign lesion with distinctive features that should enable it to be distinguished from prostatic adenocarcinoma.

Lectin Histochemistry of Ovarian Mucinous Cystadenomas

The lectin histochemistry of ovarian mucinous cystadenoma was studied using a panel of lectins comprising Triticum vulgaris, Lotus tetragonolobus, Arachis hypogaea, Griffonia simplicifolia I, concanavalin A, and Dolichus biflorus. All 23 cases examined in this study stained extensively with T. vulgaris. Of all the lectins, D. biflorus was the least reactive. Concanavalin A stained mainly the perinuclear zone, whereas the other lectins frequently stained the cytoplasm, glycocalyx, and extracellular luminal mucin. This pattern of lectin reactivity resembles endocervical more than intestinal epithelium and suggests that ovarian mucinous cystadenomas are of müllerian nature. The lack of difference in lectin reactivity between cystadenomas with and without goblet/Paneth cells supports a common histogenetic origin of both groups.

Differential Staining of Mucin Granules from Epoxy Resin Sections by a Phosphotungstic Acid-Methyl Green Procedure

After treatment of epoxy resin semithin sections from glutaraldehyde fixed rat large intestine with 5% aqueous phosphotungstic acid (PTA), staining with unpurified 0.2% solutions of methyl green at 60 C for 5 min produces a color differentiation between mucin granules of goblet cells. Some mucin granules and the glycocalyx appear deep green while the remaining granules, luminal mucin and collagen fibers are pink. The known contamination of unpurified methyl green with crystal violet seems to be responsible for the pink staining reaction of the latter structures, which also present an orange-red fluorescence under green exciting light. Electron microscopic observations show selective contrast of mucin granules which appear with a different amount of PTA deposits. This procedure is useful to reveal the heterogeneity of mucin granules in light and electron microscopy.

Intra-abdominal calcification in a fetus with cytomegalovirus infection, mimicking meconium peritonitis on ultrasound

An autopsy case is presented of a fetus with Ultra-sound (US) diagnosis of intra-abdominal calcification. Histology revealed typical Cytomegalic inclusions in nuclei and cytoplasm. A routine US detected abnormalities at 16 weeks. There was growth retardation, echogenic gut, ascites without hydrops and (paradoxically) oligohydramnios. Chromosomal analysis was normal. Meconium peritonitis was suspected. Still birth occurred at 32 weeks. At post-mortem there was no evidence of meconium peritonitis. Histology revealed cytomegalic inclusions in kidney, lung and intestinal mucosa. Numerous calco-spherites were present in luminal mucin. The features of cystic fibrosis were lacking. It appears from this case that Cytomegalovirus infection can cause changes mimicking meconium peritonitis on US.

Alterations in rat intestinal mucin patterns following luminal infusion of acetylsalicylic acid and prostaglandin derivatives

The secretion of gastrointestinal mucin and/or the formation of mucoid caps have been implicated in cytoprotective or repair mechanisms related to mucosal injury models. In this study, rats were treated with acetylsalicylic acid (ASA) or prostaglandins (PG), and their effects on the synthesis and secretion of small intestinal mucin were examined. A newly developed polyclonal antibody to rat intestinal mucin was used for immunoassay of rat intestinal luminal and tissue mucin. The mucin antigen source was obtained by vacuum aspiration of luminal mucus. A high-molecular-weight glycoprotein (2 x 10(6) Da) fraction injected into rabbits produced a primary mucin antibody. A sensitive and quantitative enzyme-linked immunosorbent assay (ELISA) was developed that yielded a highly reproducible and linear response with mucin aliquots containing 0-20 ng of protein/ml. Incorporation of the plasma tracers ([3H]glucose and [35S]sodium sulfate) into mucin derived from hexadecyltrimethylammonium bromide precipitation after treatment with ASA (100 mg/kg body wt) decreased, although administration of dimethylprostaglandin E2 (100 micrograms/kg body wt) significantly increased the specific tracer incorporation values for the sialomucin and sulfomucin indices in luminal mucin fractions. The immunoassay data pattern for the ELISA technique was virtually identical to the results of the radiolabeled tracer method obtained for the same pharmacologic treatments. These experiments demonstrate that the estimation of synthesized mucin (tissue source) or secreted mucin (luminal source) as determined by the ELISA technique is similar to that obtained by the time-consuming and labor-intensive tracer incorporation methodology.

Alteration of Gastrointestinal Mucin by Fiber Feeding in Rats

Alterations in gastrointestinal mucin induced by dietary fiber may affect nutrient bioavailability, cytoprotection of the mucosa or other aspects of gastrointestinal function. To allow quantitative study of gastrointestinal mucin, a polyclonal antibody to the mucin of the rat small intestine was produced by injecting rabbits with a high-molecular-weight subfraction (MW 2 x 10(6)) of purified mucin glycoprotein derived from rat intestinal mucin. An enzyme-linked immunosorbent assay was developed and used for the mucin assay. Three groups of male Wistar rats consumed 5% guar gum, 5% citrus fiber or a fiber-free control diet ad libitum for 4 wk. After an overnight fast, luminal and tissue mucin antibody reactivities were determined in the rat stomach, colon and small intestine. In all groups, total (luminal and tissue) mucin reactivity was greater in the small intestine than in the colon or stomach. The group fed 5% citrus fiber had significantly greater mucin reactivity in luminal samples from stomach and intestine than did the fiber-free control group. Fiber-induced increments in gastrointestinal mucin production or availability may be responsible for several reported consequences of fiber feeding, such as more rapid transit times and delayed or impaired nutrient absorption.

Ovarian endometrioid carcinomas resembling sex cord-stromal tumors. A clinicopathological analysis of 13 cases.

Thirteen endometrioid carcinomas of the ovary with predominant patterns resembling those of sex cord-stromal tumors are reported. Eight of these neoplasms had been misinterpreted by the referring pathologists as sex cord-stromal tumors, almost always of the Sertoli-Leydig cell type. The latter diagnosis was suggested by a predominance of small tubular glands or winding, elongated solid tubular structures. In four cases, the presence of luteinized cells in the tumor stroma contributed to the misinterpretation. Each specimen, however, had one or more features establishing its endometrioid nature, including large tubular glands resembling those of the typical endometrioid adenocarcinoma, foci of squamous differentiation, luminal mucin accumulation, and adenofibromatous components. Two tumors were bilateral. The age range of the patients (from 58 to 86 years) differed markedly from that of patients with Sertoli-Leydig cell tumors, who are generally much younger, as did the associated clinical manifestations, which were those of ovarian cancer in general. No androgenic effects were observed and estrogenic manifestations were evident in only one of the cases.

Clinical Significance of Mucin Extravasation in Breast Core Biopsy Specimens

Mucin extravasation (ME) refers to the presence of mucin pools in the breast parenchyma, usually resulting from ruptured ducts distended with luminal mucin. Extravasated mucin is usually seen along with cystically dilated mucin filled ducts or mucocele like lesions (MLL) of the breast. MLL is a rare lesion that may be associated with a continuum of benignity to invasive mucinous carcinoma. The purpose of this study was to document the spectrum of lesions that can be associated with ME in breast cores and to correlate with the histology in subsequent surgical excision. Thirty-seven cases with ME on image guided core biopsies were reviewed from our departmental files, and their radiologic histologic findings were noted. Twenty-six of them of them underwent subsequent open biopsies which forms the basis of this study. It was noticed that columner cell lesion (CCL) associated with mucocele like lesion (MLL) as an important finding in relation with atypia. This finding was significant regardless of their presence in calcified or non-calcified cores and also a very good statistical correlation was seen between the quantitative presence of CCL in the core and excisional biopsy diagnosis. This are support the need for excision biopsy for the cases presenting with ME in their cores. In addition, a multidisciplinary approach should also be taken for cases presenting with ME, MLL and CCL altogether in breast core biopsies even in absence of obvious cytological atypia. Key Words: Mucin ExtravasationL Columnan Cell Lesion (CCL); Mucocele Like Lesion (MLL); Fibrocystic Change (FCC); Atypical Ductal Hyperplasia (ADH); Ductal Carcinoma in Situ (DCIS) DOI: 10.3329/akmmcj.v2i1.7466 Anwer Khan Modern Medical College Journal 2011; 2(1): 15-21