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Biomedical subjects

G Mendelsohn

Publications and source records attributed to G Mendelsohn.

At least 37 records · Page 2Linked to original sources

Laminin immunostaining in hyperplastic, dysplastic, and neoplastic lesions of the endometrium and uterine cervix.

The distribution of basement membrane laminin was investigated in normal endometrium and cervix, as well as in a variety of non-neoplastic and neoplastic lesions of these tissues. Normal epithelial structures were surrounded by a generally intact basement membrane. Minor breaks in continuity and alterations of linearity were seen in association with inflammation and stromal fibrosis. Metaplasias, atypical hyperplasias, dysplasias, and in situ carcinomas characteristically rested on an essentially intact basement membrane, although minor disruptions were seen, occasionally in association with inflammation. Superficially and deeply invasive adenocarcinomas and squamous carcinomas exhibited impaired laminin production. In well differentiated carcinomas of the endometrium and cervix, an intact basement membrane was often seen around infiltrating glandular and squamous elements, although focal reduplications and small disruptions were seen in all cases. In high-grade carcinomas, considerable impairment of basement membrane integrity was seen, but immunostainable laminin was still evident, at least focally, in all cases. The findings confirm that endometrial and cervical carcinomas, even those of high histologic grade, are capable of basement membrane production.

Adenocarcinoma↗

Elaboration of nonsomatostatin peptides containing the amino-terminal portion of prosomatostatin in a somatostatin-secreting human medullary thyroid carcinoma cell line.

We identified a system, the TT human medullary thyroid carcinoma cell line which contained 74.5 +/- 26.0 ng (mean +/- SD) immunoreactive SRIH/mg protein, for studying the products of SRIH gene expression. The close homology between man and rat for the entire proSRIH and complete homology for a portion of the amino terminus (proSRIH-NTP) permitted the application of a RIA directed toward the amino terminus of rat proSRIH. Immunohistochemical studies of the human TT cell line showed that SRIH and proSRIH-NTP immunoreactivities were present in the same cells. RIA of gel filtration fractions showed that the major cellular proSRIH-NTP-containing species lack SRIH and had an apparent mol wt of 8000. A 10,000-dalton SRIH-containing species coeluting with proSRIH-NTP immunoreactivity, putative proSRIH, also was found. Similar species were found in culture medium. The major cellular and secreted form of SRIH immunoreactivity had a mol wt of 1600 (SRIH). High pressure liquid chromatography revealed that both cellular and secreted 8000-dalton proSRIH-NTP-containing material consisted of a major and several minor species. None of the species contained SRIH. The precise structure of these proSRIH-NTP-containing species and their physiological roles are not known. The fact that proSRIH-NTP-containing species are secreted suggests that they may be functional. Since the processing of proSRIH and consequently the final products appear to be tissue specific, alterations in the relative presence of different forms might reflect specific pathological processes.

Carcinoma↗

Divergent differentiation in neoplasms. Pathologic, biologic, and clinical considerations.

In this rather brief review, we have illustrated and discussed selected examples of dual or multiple differentiation within certain neoplasms. In so doing, we have attempted to present those cases which highlight common diagnostic problems and which have important biologic and clinical implications. We have shown how tumors arising in many organs such as the lung, gastrointestinal tract, and thyroid can simultaneously manifest combined endocrine-nonendocrine differentiation, and we have addressed this phenomenon in relation to the "parent cell of origin" theory. We have emphasized that while many tumors do in fact resemble the tissues in which they arise, the possession of a particular phenotype, such as endocrine, does not necessarily imply that the tumor in question was derived from an endocrine progenitor cell. To reinforce the concept that the histomorphologic, biochemical, and functional properties of tumor cells reflect ongoing differentiation events rather than a static situation, we have presented examples of tumors in which changes in phenotype have been observed during the course of disease, e.g., small cell carcinomas of the lung and prostate, as well as tumors in which divergent differentiation reflects similar lines of differentiation occurring in normal tissues, e.g., certain neurogenic tumors. Finally we have considered important clinical implications of mixed differentiation and changing phenotype and their impact on the pathologist.

Carcinoid Tumor↗

Pancreatic carcinoma with duct, endocrine, and acinar differentiation. A histologic, immunocytochemical, and ultrastructural study.

An unusual case of pancreatic carcinoma with components of poorly differentiated adenocarcinoma and islet cell tumor is reported. Histologic, immunocytochemical, and ultrastructural evidence of ductal, endocrine, and exocrine (acinar) differentiation is presented. The implications with regard to endocrine cell differentiation and the histogenesis of pancreatic neoplasms are discussed.

Adenocarcinoma↗

Papillary adenocarcinomas of the prostate. An immunohistochemical study.

Five cases of papillary adenocarcinomas of the prostate were studied for prostate-specific acid phosphatase, using the immunoperoxidase method, to determine the origin and histogenesis of these uncommon tumors. All five cases were prostatic-acid-phosphatase positive, whereas four cases showed in situ carcinoma involving large periurethral ducts. Positive immunohistochemical localization of prostate-specific acid phosphatase is useful in identifying papillary carcinoma of true prostatic origin and distinguishing them from prostatic-acid-phosphatase-negative carcinomas which may include tumors arising from periurethral glands or metaplastic urethral mucosa.

Acid Phosphatase↗

Pregnancy-specific beta-1 glycoprotein (SP-1) in breast carcinoma. Pathologic and clinical considerations.

Ectopic production of placental proteins by a variety of nontrophoblastic epithelial tumors is well recognized. Pregnancy-specific beta-1 glycoprotein (SP-1), a recently described placental protein, has been detected both in the serum and tumors of patients with breast carcinoma. To assess the significance of SP-1 in breast carcinoma, we stained 139 cases of primary breast carcinoma for SP-1 using the immunoperoxidase technique. Overall, 55 (40%) of breast cancers were positive for SP-1; focal positivity was also noted in normal breast epithelium and fibrocystic disease. Both intraductal (32%) and infiltrating duct (43%) carcinomas were more often positive than either in situ (5%) or infiltrating (26%) lobular carcinomas. SP-1 positivity in tumors of infiltrating duct morphology less than 3 cm in diameter, correlated highly (P less than 0.01) with the presence of axillary lymph node metastases. The presence of SP-1 in normal breast epithelium and fibrocystic disease and the low rate of positivity in lobular carcinoma casts doubt on the usefulness of SP-1 as a tumor marker. However, these findings suggest that immunopositivity for SP-1 in small infiltrating duct carcinomas may be an indicator of poor prognosis.

Breast Neoplasms↗

Squamous carcinoma of the foot arising in association with long-standing verrucous hyperplasia in a patient with congenital lymphedema.

A patient is reported with congenital lymphedema who developed a squamous cell carcinoma on his affected foot. Parallels are drawn between the development of a squamous cell carcinoma with condylomatous and spindle cell features arising in a setting of long-standing verrucous hyperplasia, as seen in this patient, and the well-recognized phenomenon of angiosarcoma occurring in areas of lymphangiomatous proliferation in patients with chronic lymphedema. The importance of a random genetic mutation occurring in hyperplastic tissue in an immunologically privileged site is discussed. Additional consideration is given, in the current case, to the possibility of viral oncogenesis and the role of ulceration as a promoter factor.

Carcinoma, Squamous Cell↗

Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease.

The distribution of carcinoembryonic antigen (CEA) and its relationship to calcitonin in early, localized, and disseminated (virulent) medullary thyroid carcinoma (MTC) have been studied using immunoperoxidase methods. Carcinoembryonic antigen can be demonstrated within C-cells through all stages of progression of MTC. In early disease (C-cell hyperplasia and microscopic carcinoma), CEA, and calcitonin have a similar distribution, being present in virtually every cell. Likewise, calcitonin and CEA have a similar, homogeneous distribution among cells in gross medullary carcinoma confined to the thyroid region. In both primary and metastatic tumors from patients with virulent, disseminated disease there is an inverse relationship between calcitonin and CEA distribution such that CEA expression is retained and frequently present in the greatest amounts in cells which have poor or absent staining for calcitonin, and present in the least amounts where cellular staining for calcitonin is greatest. It is postulated that in MTC expression of CEA (a marker for early epithelial differentiation), in the face of loss of calcitonin (a marker for terminal differentiation/cellular maturity), may reflect a degree of maturation block in tumors from patients with aggressive disease.

Calcitonin↗

The histogenesis of small cell carcinoma of the prostate. An immunohistochemical study.

Small cell carcinomas of the prostate are rare. A few reported cases have manifested morphologic and functional neuroendocrine characteristics, and it has been suggested that these tumors are derived from the argentaffinic/argyrophilic cells normally present in the prostate. The authors have recently studied three cases of primary prostatic small cell carcinoma in which the small cell component developed during the course of progression of "regular" prostatic adenocarcinoma, and reflected a terminal aggressive phase of the disease. Immunoperoxidase staining for prostate-specific acid phosphatase (PSAP) showed positivity in the adenocarcinoma but absence in the small cell component of each tumor. The association of small cell carcinoma with prostatic adenocarcinoma indicates that in considering the histogenesis of prostatic small cell carcinoma, a specific neuroendocrine cell of origin need not be implicated.

Acid Phosphatase↗

Intracellular Escherichia coli in urinary malakoplakia: a reservoir of infection and its therapeutic implications.

Urinary malakoplakia may pursue an aggressive clinical course with persistent infection, despite seemingly appropriate antibiotic therapy. The authors studied seven adult females with urinary malakoplakia. Specific immunocytochemical staining demonstrated intracellular Escherichia coli in malakoplakia tissue in four patients. In two of the four patients, the bacteria were present despite antibiotic-induced sterile urines at time of biopsy. Cessation of therapy consistently lead to recurrent bacteriuria in these patients. In one such patient, the intracellular bacilli were confirmed as E. coli by culture of crushed malakoplakia tissue and electron microscopic study; the organisms were a routine E. coli strain susceptible to multiple previously administered antibiotics. Only sequential treatment with bethanechol chloride and trimethoprim-sulfamethoxazole, however, eliminated the infection; all three drugs are thought to be capable of enhancing intracellular killing of bacteria. Conventional antibiotic therapy failed to halt progression of disease in other malakoplakia patients. The data indicate that intracellular bacteria may serve as a reservoir of persistent/recurrent infection in urinary malakoplakia. Optimal therapy should include therapeutic agents that may control intracellular organisms.

Adult↗

Factor VIII related antigen and glial fibrillary acidic protein immunoreactivity in the differential diagnosis of central nervous system hemangioblastomas.

Nineteen hemangioblastomas, nine angioblastic meningiomas, ten metastases to the brain (including five renal cell carcinomas), and five primary renal cell carcinomas were studied using the immunoperoxidase method for Factor VIII related antigen and glial fibrillary acidic protein (GFAP). All tumor types showed Factor VIII immunoreactivity confined to endothelial cells. Factor VIII immunostaining revealed a distinct, though probably nondiagnostic, vascular pattern for hemangioblastomas as compared with metastatic carcinomas and angioblastic meningiomas. Most of the hemangioblastomas and metastases showed numerous GFAP-reactive cells with unequivocal astrocytic morphology primarily at the interface with brain parenchyma but also occasionally deep within the tumor. Within metastases these cells often were associated with penetrating fibrovascular septa. In a minority of hemangioblastomas and metastatic carcinomas there were rare GFAP immunoreactive cells that were indistinguishable from stromal or metastatic tumor cells, respectively. Angioblastic meningiomas showed no GFAP reactivity. It is concluded that the presence of GFAP-reactive cells alone is not helpful in differentiating between hemangioblastomas and intra-axial lesions. The lack of stromal cell immunoreactivity in angioblastic meningiomas and the rare staining of stromal cells in hemangioblastomas, seen also in central nervous system (CNS) metastases, suggest that except for the endothelial cells lining vessels, these primary CNS lesions are not antigenically closely related to either endothelial cells or astroglia. Furthermore, in the evaluation of tumors within the CNS, the significance of rare GFAP-positive tumor cells must be interpreted with caution.

Cerebellar Neoplasms↗

Familial ganglioneuromatous polyposis of the large bowel. Report of a family with associated juvenile polyposis.

The unique familial occurrence of polypoid intestinal ganglioneuromatosis of the large bowel is reported. The lesions affected a 38-year-old father and three children aged 14, 12, and 10 years. In these cases, extensive diffuse and polypoid proliferation of nerve fibers and ganglion cells within the colonic mucosa was associated with pronounced epithelial changes resembling juvenile polyposis. None of the patients had any clinical evidence of the mucosal neuroma syndrome or Von Recklinghausen's neurofibromatosis, conditions in which intestinal ganglioneuromatosis can occur. The question of whether the juvenile-type polyps are hamartomatous or whether they represent a reactive process is addressed.

Adolescent↗

Signet-cell-simulating microfollicular adenoma of the thyroid.

A rare microfollicular adenoma of the thyroid gland with mucinous signet-cell features is described. Mucin stains demonstrate the presence of neutral mucin within some tumor cells. Immunohistochemical staining for thyroglobulin demonstrates strong thyroglobulin positivity within virtually all tumor cells, confirming the follicular-cell nature of the tumor. This tumor is contrasted with other, previously reported mucin-producing tumors of the thyroid.

Adenoma↗

Human medullary thyroid carcinoma in culture provides a model relating growth dynamics, endocrine cell differentiation, and tumor progression.

We used an unique model, human medullary thyroid carcinoma (MTC) in culture (the TT line), to study features of neuroendocrine-related biochemistry in relationship to growth, differentiation, and tumor progression. Tumor tissues from patients with virulent MTC contain a very heterogeneous distribution of cells staining for calcitonin (CT) and have a high ratio of intracellular L-dopa decarboxylase activity (DDC) to CT. We found, in a culture line of MTC derived from a patient with virulent disease, that the degree of the inverse relationship between DDC and CT and the heterogeneous cellular distribution of CT probably relate to the rate of cellular growth and the biochemical set of individual cell clones. During exponential growth of the parent TT cell line, intracellular DDC and CT varied. DDC increased by 70% and CT decreased by 40%. Single time-point measurements in 54 cell clones or highly enriched cell populations revealed a more dramatic variability for CT (15-fold) than for DDC (5-fold). During growth of the clones having the highest and lowest CT measurements, respectively, inverse dynamics between DDC and CT were again found. However, each clone maintained a distinct range of CT during the entire growth curve, with a 2- to 4-fold difference in CT between the two clones throughout. In the low producing CT clone, ratios between DDC and CT rose to greater than 1.0 during growth, a very high value found before this study only in MTC tissues from patients with virulent disease. Immunohistochemical staining for CT of parent cells and clones grown on embryonic chick skin revealed increased cellular heterogeneity for CT distribution during growth. The TT line provides a powerful tool to study neuroendocrine related biochemical events in relationship to growth, differentiation, and tumor progression in MTC. Our in vitro findings in the TT line well explain observations made previously in patients. We conclude that: (1) DDC, a neural property of MTC, is an early differentiation marker as compared to CT and that the differentiation status of MTC cells varies inversely with cell growth rate; and (2) in patients with MTC, the virulence of the tumor probably varies inversely with differentiation status. The inverse ratio of DDC to CT is probably determined in MTC by the proportion of rapidly growing cells and numbers of cell clones which have a poor ability for maturation.

Calcitonin↗

The distribution of carcinoembryonic antigen in breast carcinoma. Diagnostic and prognostic implications.

Carcinoembryonic antigen (CEA) has been shown to be a useful tumor marker in patients with breast carcinoma. The unlabeled antibody immunoperoxidase technique was used to localize CEA in 93 cases of primary breast carcinoma, 15 cases of atypical duct papillomatosis, and 4 cases of duct papilloma. Normal breast epithelium and breast epithelium in fibrocystic disease did not stain positively for CEA. Twenty-four of 27 (88%) intraductal carcinomas, and 47 of 69 (68%) infiltrating duct carcinomas were CEA positive. In contrast, only 5 of 21 (23%) in situ lobular carcinomas and 8 of 24 (33%) infiltrating lobular carcinomas were positive for CEA. All 15 cases of atypical epithelial papillomatosis were negative, whereas 1 of the 4 cases of duct papilloma exhibited microscopic foci of weak CEA positivity. There was a trend for infiltrating duct carcinomas, 3 cm in diameter or smaller, staining strongly positive for CEA, to be associated with synchronous axillary lymph node metastases (P = 0.09). Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region and even from cell to cell. Positive immunohistochemical staining for CEA may play an adjunctive role in discriminating intraductal carcinoma from atypical papillary ductal proliferations.

Breast Neoplasms↗

Intraocular lymphomas. Natural history based on a clinicopathologic study of eight cases and review of the literature.

Eight patients with intraocular lymphoma were studied; all were middle-aged or elderly, usually presenting with a unilateral visual deficit. All patients also had an extraocular lymphoma with either systemic (2) or isolated central nervous system (CNS) involvement (6). When ocular symptoms preceded CNS symptoms, they presented from 11 months to 10 years earlier. Intraocular lymphoma tended to affect the eye ipsilateral to the CNS tumor either exclusively or initially, and to the greatest degree histologically. Histologic examination of intervening optic pathways revealed extension of intraocular tumor across the optic nerve into orbital leptomeninges in 3 cases. Corresponding CNS tumors showed prominent leptomeningeal involvement. All intraocular and extraocular tumors showed diffuse growth patterns with histiocytic (large cell), poorly differentiated lymphocytic or mixed lymphocytic-histiocytic subtypes. CNS tumors were detected only after onset of neurologic symptoms, and were almost always fatal, although CNS irradiation prolonged survival for years in some cases. Our data suggest that the peculiar link between intraocular and CNS lymphomas may reflect both multicentric and metastatic disease processes. The prompt recognition of intraocular lymphomas as a harbinger of extraocular tumor may prove valuable in earlier recognition and treatment of the disease.

Aged↗

Analysis of cell surface proteins delineates a differentiation pathway linking endocrine and nonendocrine human lung cancers.

We have previously determined that the cell surface protein phenotype distinguishes human small cell lung carcinoma (SCC), a neoplasm with endocrine properties, from non-SCC in culture. We now demonstrate that cloned cell cultures of human large cell undifferentiated lung carcinoma, established directly from a patient with mixed SCC and non-SCC, simultaneously express surface proteins characteristic of SCC and non-SCC lung cancer cells. Hence, SCC and a form of large cell carcinoma appear linked through a continuum of differentiation events that: (i) may explain clinically important transitions that occur between the major types of human lung cancer and (ii) provide evidence for a common cellular origin of endocrine and nonendocrine cells in the bronchial mucosa.

Amine Oxidase (Copper-Containing)↗