The glycosphingolipids of human prostate tissue.

Neutral glycolipids and gangliosides from surgical samples of benign human prostate tissue were analyzed by chemical, enzymatic and immunostaining procedures. The neutral glycolipids consisted of ceramide mono-, di-, tri- and tetrahexosides of the globo series plus paragloboside. The monosialoganglioside fraction contained GM3 and GM1 plus multiple species of monosialylated lactosamine-containing structures, including sialyl-alpha-2----3paragloboside plus at least two compounds having a non-reducing terminal sialyl alpha 2----6Gal linkage. The disialoganglioside fraction contained GD3 as the major component plus GD1a, GD2 and GD1b. GT1b was the major trisialoganglioside.

Crystallization and purification of the enzyme anthranilate phosphoribosyl transferase.

Anthranilate phosphoribosyl transferase from the bacterium Hafnia alvei has been crystallized. This enzyme is one of a small number that constitute the biosynthetic pathway for tryptophan. Large cubic crystals were grown at 4 degrees C by dialyzing away the glycerol from a protein solution that included ammonium sulfate, polyethylene glycol and glycerol. The crystals were much more temperature stable and resistant to X-ray deterioration than a previous, similar crystal form that had included glycerol. The crystals belong to the space group I432, a = b = c = 189 A (1 A = 0.1 nm). The ratio of the monomer molecular weight, 37,000, to the volume of the unit cell suggests that there is one homodimer per asymmetric unit. The crystals diffracted to a resolution of 3.0 A at the Stanford Synchotron Radiation Laboratory X-ray source.

The presence and estrogen control of immunoreactive calbindin-D9k in the fallopian tube of the rat.

The present study was undertaken to localize and investigate the endocrine control of immunoreactive 9K calbindin-D9k in the fallopian tube (oviduct) of the rat. Rat fallopian tubes were excised with the uterus, immediately fixed by freeze-substitution, and processed for immunoperoxidase staining. Staining employed a rabbit antiserum against purified rat intestinal calbindin-D9k and the streptavidin-biotin technique. Calbindin-D9k immunoreactivity was localized to luminal epithelial cells of the fallopian tube of mature rats, with no staining observed in other tissue layers of the tube. Epithelial cells in both the isthmus and the ampulla were positive for calbindin-D9k. In weanling rats, which have little ovarian function but high levels of 1,25-dihydroxyvitamin D, no immunoreactive calbindin-D9k was observed in any part of the tube. However, after daily injections of estradiol (6 micrograms/day) for 3 days, intense staining was observed in the epithelial cells of the immature rat fallopian tube. Progesterone treatment (1 mg/day for 3 days) of immature rats had no effect on calbindin-D9k in fallopian tube. The lumen of the fallopian tube (oviduct) is the key location for fertilization, a process that requires a narrowly defined concentration of extracellular calcium. By analogy to the intestine, calbindin-D9k may play a role in the transcellular movement of calcium across the fallopian tube epithelium in the fallopian tube lumen.

Vitamin D-dependent calcium binding protein in rat uterus: differential effects of estrogen, tamoxifen, progesterone, and pregnancy on accumulation and cellular localization.

The present studies were undertaken to characterize the expression of calcium binding protein (CaBP or calbindin-D9k) in uterine tissues. Using immunohistochemical techniques, calbindin-D9k was localized to the uterine (luminal) epithelium of pregnant rats, but not present in the uterine epithelium of nonpregnant rats. Calbindin was found also in the uterine smooth muscle and endometrial stromal cells of pregnant animals. These latter localizations were reproduced in uteri of 21-day-old nonpregnant rats by administration of tamoxifen or physiological doses of estrogens. Estrogen and tamoxifen produced half-maximal increases of uterine calbindin at daily doses of 0.1 and 10 micrograms, respectively, and maximal responses at 0.3 and 40 micrograms/day. Testosterone and progesterone, at doses which increased the growth of the uterus, did not induce calbindin-D, and both hormones blocked estradiol's effect on uterine calbindin-D appearance. The epithelial localization of calbindin in pregnant uteri was not reproduced in nonpregnant animals by either estradiol (3 micrograms/day) or progesterone (1 mg/day). The localization of calbindin in uterine epithelium during pregnancy appears to be dependent upon an as yet unknown factor. In view of the large surface area of the luminal epithelium in pregnant animals, and the pregnancy-related expression of calbindin in these cells, we propose that uterine epithelium plays an important role in transport of calcium during pregnancy.

Estrogen inhibits calbindin-D28k expression in mouse uterus.

The cellular localization and hormonal controls of calbindin-D9k expression in the rodent reproductive tract have suggested new functions for this protein. The present studies were undertaken to extend the earlier studies of calbindin-D9k to the related protein, calbindin-D28k. Immunohistochemical studies revealed that calbindin-D28k was absent from female rat reproductive tissues, but was abundantly expressed in immature mouse uterus and oviduct. Immunoreactivity was restricted to the endometrial and glandular epithelium of the uterus and the oviductal epithelium. Neither 1,25-dihydroxyvitamin D- nor strontium-containing diets (to blunt 1,25-dihydroxyvitamin D production) affected expression of calbindin-D28k. Uterine, but not oviductal, calbindin-D28k decreased markedly at sexual maturity; this pattern persisted in pregnant mice and was reproduced in immature mice by the administration of estradiol (3 micrograms/day for 3 days). RNA extraction and Northern analyses demonstrated that estrogen markedly decreased calbindin-D28k mRNA abundance in the uterus, but not in the oviduct. These findings suggest that estrogen affects mammalian calbindin-D28k expression and represent a rare example of estrogen-induced down-regulation of gene expression.

Effects of rat adrenal homogenate on induction of atherosclerosis in cholesterol-fed rabbits.

Virgin male Sprague-Dawley rats are resistant to atheroma formation. An adrenal homogenate from such rats delayed the increase in serum cholesterol concentrations in cholesterol-fed New Zealand white rabbits. More importantly, aortic atherosclerosis was markedly reduced when compared to a similar population fed cholesterol without adrenal homogenate for 14 weeks. The nature of the active constituent in this homogenate and its mode of action are unknown.

Plasmacytoid monomorphic adenoma of salivary glands. Absence of myogenous differentiation and comparison to spindle cell myoepithelioma.

The immunohistochemical and ultrastructural features of two salivary gland monomorphic adenomas composed of plasmacytoid cells (so-called plasmacytoid myoepitheliomas) were studied to determine if the plasmacytoid cells contained detectable evidence of myogenous differentiation. The results were compared with the immunohistochemical profile of three salivary gland myoepitheliomas of spindle-cell type. The plasmacytoid tumors were each immunoreactive for vimentin, cytokeratin, S100 protein, and glial fibrillary acidic protein (GFAP). They were negative for muscle-specific actin (MSA), smooth-muscle actin (SMA), and desmin. Conversely, two of three spindle-cell myoepitheliomas were immunoreactive for MSA and SMA, in addition to vimentin, cytokeratin, and S100 protein. One tumor also contained focal positivity for desmin and GFAP, and a single spindle-cell tumor was vimentin-positive only. Ultrastructurally, plasmacytoid cells were characterized by focal desmosomes, basal lamina, and abundant intermediate cytoplasmic filaments. Dense bodies typical of smooth-muscle cells and actin-sized filaments were absent. Immunohistochemically and ultra-structurally, the plasmacytoid cells lack any evidence of myogenous differentiation and should not be considered a subtype of myoepithelioma.

Colorectal carcinoma in the first three decades of life.

Sixteen cases of colorectal adenocarcinoma in patients 30 years of age and younger were treated at the University of Virginia Medical Center between 1957 and 1977. Ten patients (63%) were black, and seven patients (44%) were black females. The high incidence of this tumor in young blacks in our patient population appears to be a recent development, becoming clinically manifested since 1965. Pain was the major presenting symptom, and bleeding was a constant finding in the patients with rectosigmoid lesions. Eighty-six percent had metastases at the time of diagnosis despite a short duration of symptoms. Five-year survival in 11 patients with mucinous adenocarcinoma was 18%, while the three patients with well-differentiated glandular carcinoma had a 5-year survival of 33%. Material was unavailable for histologic review in two cases. Fourteen of 16 patients eventually died of their carcinoma, and one patient died of malignant lymphoma. Additional factors which correlated with length of survival were resectability, extent of bowel wall invasion, and the presence of lymph node capsular invasion. Nodal capsular invasion is an especially sensitive marker for short-term survival and has not been previously reported in colonic tumors.

Olfactory neuroblastoma. A clinicopathologic study of 21 cases.

The clinicopathologic features of 21 olfactory neuroblastomas are reviewed with emphasis on variables of potential diagnostic or prognostic value. The patients ranged in age from 9 to 66 years (median: 49 years); 57% were women. At the time of diagnosis, one tumor was Kadish stage A, 11 were stage B, and nine were stage C. Nineteen patients had extensive surgical resections, but in six instances these were considered incomplete. Six patients (29%) developed local recurrences and eight (38%) had metastases. Ten patients (48%) were alive and free of disease from 10 to 239 months (median: 58 months) after diagnosis. Seven (33%) died of tumor, with a duration of survival ranging from 1 to 142 months (median: 27 months). A fibrillary intercytoplasmic back-ground was the most useful diagnostic feature microscopically and was present, at least focally, in 18 of 21 tumors. A silver stain for neuronal processes was helpful when fibrils could not be seen on hematoxylin- and eosin-stained sections. Homer-Wright rosettes, when present, also aided in diagnosis but were well formed in only six tumors. The only clinical feature that correlated with prognosis was whether the neoplasm had been completely excised at initial presentation. Tumor necrosis was the only histologic feature correlating with prognosis, but neither association was statistically significant. Metastases, clinical stage, mitotic rate, and nuclear pleomorphism showed no relationship to survival in this series.

Verruca vulgaris of the larynx: a distinctive lesion of probable viral origin confused with verrucous carcinoma.

Two adult males had superficial, keratotic vocal cord lesions. One was diagnosed as verrucous carcinoma, prompting a hemilaryngectomy. The other was interpreted as a squamous papilloma and was treated by local excision. Both patients are disease-free 7 years and 18 months, respectively, following surgery. The histologic features of both lesions are identical to those of cutaneous verruca vulgaris, and immunoperoxidase staining for human papilloma virus was positive in one case. Laryngeal verruca vulgaris has not been previously described and in the past may have been misdiagnosed as verrucous carcinoma, leading to unnecessary surgery. The histologic features of laryngeal verruca vulgaris are presented and its distinction from other cytologically bland, keratotic lesions of the larynx is discussed.

Unusual adenomatous polyps in juvenile polyposis coli.

A 14-year-old boy had an ileocolectomy for juvenile polyposis coli. Twenty-five years later he developed peculiar adenomatous polyps in his rectum. The polyps had irregularly shaped glands lined by cells with stratified, atypical nuclei. Some glands were distended with mucus, but otherwise the polyps did not resemble juvenile polyps. Two other types of polyps associated with juvenile polyposis coli and often designated as adenomatous polyps are illustrated. A solitary juvenile polyp with foci of hyperplastic and adenomatous change is also depicted, and the association of juvenile polyps with colonic neoplasia is reviewed.

Histiocytoid (epithelioid) hemangioma of the testis. The so-called vascular variant of "adenomatoid tumor".

Adenomatoid tumors are well-recognized neoplasms generally considered to be of mesothelial derivation. We describe an unusual vascular neoplasm that arose in the testis of a 29-year-old and resembled an adenomatoid tumor by light microscopy. An orchiectomy was performed, and the patient is alive and disease-free 3 years later. The 2-cm tumor was composed of small tubules lined by mesothelial-like cells with uniform, vesicular nuclei. However, some lumina contained erythrocytes, and immunohistochemically, the luminal cells reacted with antibodies to vimentin, Factor VIII-related antigen, and Ulex europaeus I lectin but not cytokeratin or epithelial membrane antigen. A cuff of muscle-specific actin-positive cells surrounded the luminal cell layer. This adenomatoid-like vascular neoplasm is more properly interpreted as a histiocytoid (epithelioid) hemangioma. Although some authors have considered microscopically similar lesions to represent a vascular variant of adenomatoid tumor, we prefer to reserve the term "adenomatoid tumor" for microscopically appropriate proliferations that have mesothelial features.

Middle ear adenoma. A cytologically uniform neoplasm displaying a variety of architectural patterns.

Seven patients with middle ear adenomas (MEA) are presented. MEA are cytologically stereotyped neoplasms with a spectrum of architectural patterns. All tumors were composed of uniform, round, or ovoid cells that resembled normal middle ear epithelium. The histologic patterns varied from tumor to tumor and within a single lesion. Broad sheets of tightly packed cells were commonly present, but glandular and cribriform areas were also frequent. Complex, interdigitating trabeculae, rows of individual cells, and dissociated cells were sometimes seen. Grimelius argyrophil stains were focally positive in three of five stained tumors, but Churukian-Schenk argyrophil preparations demonstrated only rare positive cells in two of these cases. Lysozyme was demonstrable immunohistochemically in each tumor. Lysozyme is present in normal middle ear epithelium and may be a useful marker for MEA, since the tumor is apparently derived from these cells. The clinical features of the seven cases that we report are combined with 44 MEA from the literature. MEA seldom recurs after excision and very rarely invades bone. No patient died of disease. The clinical and histologic distinction of these tumors from plasmacytoma, paraganglioma, ceruminoma, carcinoid tumor, and papillary carcinoma is discussed.

Histologic classification of sinonasal intestinal-type adenocarcinoma.

Kleinsasser and Schroeder recently described a histologic classification system for woodworker-associated, intestinal-type adenocarcinomas of the sinonasal region. To determine if their approach is easily applied and prognostically meaningful for both woodworker-associated and sporadic intestinal-type adenocarcinomas in the sinonasal region, we analyzed 15 such cases. The 12 men and three women ranged in age from 37 to 75 years. Only four were woodworkers. All tumors arose in the nasal cavity or paranasal sinuses. The three authors independently classified the tumors with unanimous agreement in 11 (73%) of 15 cases. Disagreements were resolved by group review and consensus. Ten tumors were papillary tubular cylinder cell type; these were subdivided into grades I (four cases) and II (six cases) on the basis of cytologic atypia. Three tumors were alveolar goblet cell type; one tumor was signet-ring type; and one had a mixed pattern. Median survivals were papillary tubular I, 9 years; papillary tubular II, 3 years; and alveolar goblet cell, 7 years. It is concluded that this classification system is easy to apply, reproducible, and appears to identify a group of sinonasal intestinal-type adenocarcinomas (papillary tubular I) with a prolonged survival.

Uterine intravascular menstrual endometrium simulating malignancy.

Intravascular menstrual endometrium, a rare finding in hysterectomy specimens, can pose clinically critical differential diagnostic problems. We describe a 28-year-old female with cervical dysplasia and numerous foci of menstrual endometrium in the parametrial blood vessels of her subsequent hysterectomy specimen. Histologically, the intravascular tissue consisted of small spindled stromal cells, larger cuboidal epithelial cells, or both components in close association. Immunohistochemically, the small spindled cells were vimentin positive and the larger cuboidal cells stained with epithelial markers. Distinction of intravascular menstrual endometrium from intravascular malignancies such as carcinoma, sarcoma, or lymphoma may be difficult, especially at the time of frozen-section diagnosis. Awareness of this process, attention to its cytologically bland, usually biphasic appearance, knowledge of the menstrual status, and application of appropriate immunohistochemical markers will allow distinction from neoplasia.

An immunohistochemical study of normal endometrial stroma and endometrial stromal neoplasms. Evidence for smooth muscle differentiation.

To determine the immunohistochemical staining profile of endometrial stromal cells, we analyzed a series of formalin-fixed, paraffin-embedded normal endometrial tissues, stromal nodules, and stromal sarcomas for immunoreactivity with a panel of eight antibodies. Normal proliferative-phase (five cases) and secretory-phase (five cases) endometrial stromal cells showed the following immunopositivity: vimentin 10 of 10, muscle-specific actin (MSA) 10 of 10, alpha-smooth muscle actin (alpha sm) 10 of 10, desmin nine of 10, cytokeratin (AE1/AE3 and CAM 5.2) zero of 10, epithelial membrane antigen (EMA) zero of 10, and S-100 protein zero of 10. Antibodies to vimentin, MSA, and alpha sm stained a greater number of proliferative-phase stromal cells as compared with secretory-phase cells. Only rare stromal cells were immunoreactive for desmin, except for one case in which predecidual cells were diffusely positive. Both endometrial stromal nodules reacted with antibodies to MSA, alpha sm, and desmin, and one was vimentin positive. Each was unreactive for epithelial markers and S-100 protein. The 12 endometrial stromal sarcomas had the following immunopositivity: vimentin 11 of 12, MSA 10 of 12, alpha sm 10 of 12, desmin seven of 12, AE1/AE3 one of 12, CAM 5.2 two of 12, EMA zero of 12, and S-100 protein zero of 12. The antibodies to MSA and alpha sm usually stained a greater number of cells than did the desmin antibody. Three stromal sarcomas had sex cord-like areas, one of which exhibited focal CAM 5.2 positivity. These immunohistochemical findings for normal and neoplastic endometrial stromal cells indicate smooth muscle differentiation and are similar to those of smooth muscle neoplasms and myofibroblastic cells.

Lobular capillary hemangioma: the underlying lesion of pyogenic granuloma. A study of 73 cases from the oral and nasal mucous membranes.

Pyogenic granuloma (PG) has a diagnostic, lobular arrangement of capillaries at its base. The lobules consist of discrete clusters of endothelial cells, and the lumina vary from indistinct to prominent. The superficial portions of the lesion may undergo secondary, nonspecific changes including stromal edema, capillary dilation, inflammation, and a granulation tissue reaction. PG has often been equated with these inflammatory changes but objective diagnostic criteria have not been presented. To avoid confusion and focus on the intrinsic nature of PG we suggest the accurate, descriptive term, lobular capillary hemangioma (LCH). A review of 639 vascular lesions of the oral cavity and upper respiratory tract yielded 73 cases with the characteristic features of LCH. The lip was the most common site (38%), followed by the nose (29%), oral mucosa (18%), and tongue (15%). LCH usually presents as a spontaneous, painless, bleeding mass. There is a predilection for males less than 18 years old, females in the reproductive years, and an equal sex distribution beyond 40 years of age. No examples of LCH were found in 68 vascular lesions from the larynx or trachea.

Aggressive papillary tumor of middle ear/temporal bone and adnexal papillary cystadenoma. Manifestations of von Hippel-Lindau disease.

The occurrence of an aggressive papillary middle ear/temporal bone tumor (APMET) and a benign adnexal papillary tumor of probable mesonephric origin (APMO) in a patient with von Hippel-Lindau disease (VHL) is reported. Histologically, both tumors were identical to papillary cystadenomas of the epididymis and broad ligament of probable mesonephric derivation. A comprehensive literature review showed that including the current case, seven of 46 (15%) documented cases of APMET and four of four (100%) cases of APMO arose in patients with VHL. Given an estimated minimum birth incidence of 1/36,000, a one-sample test of binomial proportion using the exact method establishes that the association of APMET and APMO with VHL is highly significant (p = 1.4 x 10(-24) and 1 x 10(-18), respectively). The data indicate that APMET and APMO may represent major visceral manifestations of VHL. Accordingly, in the presence of one of these tumors strong consideration should be given to the diagnosis of VHL, given either the presence of another major component of VHL or documentation of VHL in at least one consanguineous relative.

Intraarticular synovial sarcoma.

A 43-year-old man presented with decreased range of motion in his left knee and a painful medial joint mass that was grossly visible. Arthroscopy demonstrated a mobile, flat mass 3 cm in diameter in the knee joint that seemed to be loosely tethered to the synovium. The mass was excised, and light microscopic examination demonstrated a biphasic synovial sarcoma. There was no transition with the attached normal synovium. Immunohistochemically, the epithelial component was intensely positive for epithelial membrane antigen and cytokeratins (CAM 5.2 and AE 1/AE 3), and the spindle cell component was focally positive for these markers. The patient has no evidence of disease 9 years after only local excision. Although the term synovial sarcoma suggests a relationship to normal synovium, only rarely has truly intraarticular disease been reported.

Small-cell undifferentiated carcinoma of the colon. A clinicopathological study of five cases and their association with colonic adenomas.

Colonic small-cell undifferentiated carcinoma (SCUC) is an extremely aggressive neoplasm. We describe five patients with colonic SCUC and review five additional, well-documented cases. The longest known duration of survival is 14 months and all patients with follow-up of this duration have died of disease. Regional lymph nodes are invariably involved at the time of diagnosis and when distant metastases were present, the liver was always affected. Four of our cases of SCUC arose in association with colonic adenomas and in two of these the SCUC component was confined to the superficial submucosa. Yet, both produced regional metastases and one had massive hepatic involvement. Ultrastructurally, colonic SCUC exhibits divergent, predominantly neuroendocrine differentiation. The ultrastructural features and association with colonic adenomas suggest an endodermal rather than neuroectodermal derivation.