Fluctuating flank tumor in a young woman.
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Adult↗
Biomedical subjects
V A Memoli
Publications and source records attributed to V A Memoli.
Coagulation-cancer interaction in situ in renal cell carcinoma.
Fibrin was detected by immunospecific techniques associated with both intravascular and extravascular tumor deposits in renal cell carcinoma. In addition, coagulation factors VII and X were demonstrated in intercellular spaces within tumor tissue and adjacent to the surface of tumor cells. Scant accumulation of platelets on intravascular tumor masses was observed. These data suggest that tumor cells in renal cell carcinoma may induce fibrin formation locally by a factor VII-mediated (and thus tissue factor-initiated) pathway of blood coagulation. This mechanism may also account for the hypercoagulable state that exists with this tumor type. We postulate that local fibrin formation may contribute to the growth and spread of this particular type of cancer and that the course of renal cell carcinoma may be ameliorated by anticoagulant therapy.
Antibodies↗
Paragangliomas of the head and neck: ultrastructural and immunohistochemical analysis.
Eighteen head and neck paragangliomas were studied by light microscopy and light microscopic immunohistochemistry by the peroxidase technique for the presence of NSE (neuron-specific enolase), serotonin, and a battery of neuropeptides. Seven of these tumors were also studied by electron microscopy. All 18 cases demonstrated immunostaining for NSE; 10 of the 11 carotid body tumors had immunostaining for multiple hormones. Considering all 18 cases, the most frequently demonstrated hormonal substances were in order: serotonin, leu-enkephalin, gastrin, substance P, vasoactive intestinal polypeptide (VIP), somatostatin, bombesin, calcitonin, and alpha MSH. In several tumors, adjacent-step sections stained for different hormonal substances strongly suggested reactivity for more than one hormone in given tumor cells. By electron microscopy, all 7 cases studied displayed considerable heterogeneity of the neurosecretory granules with respect to size, shape, and electron density. This demonstrated that branchiomeric paragangliomas are capable of producing a spectrum of neuropeptides in addition to their known amine content. The presence of immunoreactive serotonin in most of these neoplasms was confirmed. In addition to these findings, neurofibrils within the substance of carotid body paragangliomas demonstrated immunoreactivity for somatostatin and a gastrinlike neuropeptide. The significance of the neuropeptides in these neoplasms and their possible presence and role in normal and hyperplastic paraganglia remain to be defined.
Carotid Body Tumor↗
Breast carcinomas with neuroendocrine differentiation.
Twenty-two breast carcinomas with membrane bound granules by electron microscopy were tested for the presence of neuron specific enolase (NSE), neuropeptides and serotonin by immunohistochemistry. By light microscopy the cases studied included infiltrating ductal carcinomas, intraductal carcinomas, apocrine carcinomas, infiltrating lobular carcinomas of both classical and alveolar types, mixed lobular/colloid carcinomas, carcinoid growth pattern and one unclassified carcinoma. Ten cases showed immunoreactivity for 1 or 2 neuropeptides in scattered cells whereas all cases were positively and rather diffusely stained with anti-NSE. Immunohistochemical staining at the ultrastructural level was carried out; the presence of neuropeptides could not be confirmed. Scattered granules were marked with gold particles when antiserum against casein was used. We conclude that neither argyrophilia, nor NSE immunoreactivity nor membrane bound granules seen by electron microscopy constitute at present sufficient evidence to designate a breast carcinoma as neuroendocrine. However, our study indicates that certain breast carcinomas of several types do include cells with neuroendocrine features demonstrable convincingly by light microscopic immunohistochemistry. We have no evidence that these breast carcinomas with neuroendocrine features behave differently from their counterparts lacking such features. The intriguing speculation is that neuropeptides produced by certain breast carcinomas may act as local modulators of tumor growth and differentiation.
Adult↗
Neuroendocrine neoplasms of the bronchopulmonary tract. A classification of the spectrum of carcinoid to small cell carcinoma and intervening variants.
Eighty-one primary pulmonary neuroendocrine neoplasms were assessed by the classification of Gould and associates. The neuroendocrine features of these tumors were studied by a combination of conventional light microscopy, electron microscopy, and immunohistochemical staining for hormonal substances and neuron-specific enolase. In each case, clinical follow-up was obtained to test the prognostic value of this new pathological classification. This study indicated that bronchial carcinoids are very low-grade neuroendocrine neoplasms that are locally invasive and only occasionally metastasize late in their course. Well-differentiated neuroendocrine carcinomas are relatively low-grade carcinomas that either present with or subsequently develop nodal or distant metastases in 73% of patients. Intermediate cell neuroendocrine carcinomas are highly aggressive tumors often mistakenly called "large cell undifferentiated carcinoma." Their clinical course is comparable to that of small cell neuroendocrine carcinomas, which has a mean survival of 9 months. The different clinical courses of these tumors demonstrate the predictive value of the proposed classification. It appears particularly valuable to identify well-differentiated neuroendocrine carcinoma as a low-grade carcinoma, distinct from true bronchial carcinoids. This classification may resolve some discrepancies regarding the therapy for and prognosis of "carcinoids" and their presumed variants.
Biopsy↗
Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. I. Carcinoids.
Twenty-five strictly defined bronchopulmonary carcinoids were studied by light microscopic immunohistochemistry by the peroxidase technique for NSE (neuron-specific enolase), serotonin, and a broad spectrum of neuropeptides. Eighteen cases were also studied by electron microscopy. Twenty-three of the twenty-five cases showed immunostaining for NSE; 24 cases displayed immunostaining for at least two of the hormones tested for; the single case that failed to show hormonal immuno-reactivity was however positive for NSE and had granules by electron microscopy. Serotonin was the most frequently demonstrated hormone followed by bombesin, vasoactive intestinal peptide, gastrin, leu-enkephalin , alpha-melanocyte stimulating hormone, somatostatin, substance P, and calcitonin. In several cases, adjacent-step sections stained for different hormones strongly indicated immunoreactivity for more than one hormone in single neoplastic cells. By electron microscopy, all 18 cases studied showed generally abundant neurosecretory granules, which, however, displayed considerable heterogeneity in their size, shape, and density. Twelve of these eighteen cases displayed evidence of squamous differentiation and 10 showed characteristic exocrine lumina. The capability of single neuroendocrine tumors and single neuroendocrine tumor cells to produce more than one immunoreactive hormone is hereby amply confirmed; these broad capabilities are certainly reflected in the heterogeneous granule populations seen by electron microscopy. The synchronous presence of squamous and exocrine features in broncho-pulmonary carcinoids indicates that they too are capable of multidirectional differentiation, which should not detract from their being regarded basically as well-differentiated neuroendocrine neoplasms. The clinical significance of strictly defining bronchial carcinoids is underscored by the fact that of 25 cases followed for 2-13 years, only one developed metastases 9 years postoperatively.
Bronchial Neoplasms↗
Immunohistochemical and ultrastructural analysis of bronchopulmonary neuroendocrine neoplasms. II. Well-differentiated neuroendocrine carcinomas.
We have attempted to characterize a group of bronchopulmonary neoplasms that share certain structural features with true carcinoids but appear distinctly more pleomorphic and behave far more aggressively. In reviewing our files from 1973 to 1982, 11 such neoplasms were identified; the original diagnoses were "atypical bronchial carcinoid" (3 cases), "malignant carcinoid" (1 case), "bronchial carcinoid" (3 cases), "peripheral carcinoid" (2 cases), and "peripheral oat cell carcinoma" (2 cases). Of the 11 neoplasms, 5 were central and 6 were peripherally located. At presentation, 7 patients had lymph node metastases and 1 had a distant metastasis. No patient had a conventionally defined hormonal syndrome; however, 2 patients had a history of episodic flushing, one of which was associated with diarrhea. All cases were studied by light microscopy and light microscopic immunohistochemistry for NSE (neuron-specific enolase), serotonin, and broad-spectrum neuropeptides. Five cases were studied by electron microscopy. By light microscopy, the tumors were composed of solid clusters of polygonal to fusiform cells in an evident organoid arrangement. Foci of glandular and/or squamous differentiation were seen in 7 cases. Pleomorphism was moderate and mitoses were readily found. Focal necrosis was seen. By immunohistochemistry, 10 cases expressed NSE immunoreactivity. All cases demonstrated hormonal immunoreactivity; in 9 cases, immunoreactivity for more than one hormone was observed. The hormones most frequently expressed were serotonin, bombesin, gastrin, leu-enkephalin, and ACTH. By electron microscopy, all cases studied contained heterogeneous populations of neurosecretory granules; the latter, however, were not abundant and tended to aggregate either in the basal pole of the cells or, more frequently, interlacing "dendritelike" cytoplasmic processes. Aggregates of intermediate filaments were frequently seen. Basal lamina deposition was seen but gaps and larger areas of discontinuity were frequent. We believe that these neoplasms constitute a distinct pathologic entity for which the term "well-differentiated neuroendocrine carcinoma" has been proposed. Clinically, these tumors merit special attention since they are demonstrably more aggressive than true carcinoids but are distinctly less malignant than the intermediate or small cell variants of neuroendocrine carcinoma.
Adult↗
Glial fibrillary acidic protein (GFAP) immunoreactivity in peripheral nerve sheath tumors.
A spectrum of 24 benign and malignant nerve sheath tumors and 10 non-neural spindle-cell tumors were studied by light microscopy for the presence of glial fibrillary acidic protein (GFAP) immunoreactivity by the peroxidase-antiperoxidase (PAP) technique. In 8 cases, these results were compared to their electron microscopic appearances. Seventy percent (7 of 10) of benign schwannomas and 50% (4 of 8) of benign neurofibromas demonstrated focal to diffuse GFAP immunoreactivity. None of the malignant nerve sheath tumors nor any of the non-neural spindle-cell neoplasms contained demonstrable GFAP immunoreactivity. Similarly, no GFAP immunoreactivity could be detected in Schwann cells in normal peripheral nerves. The solitary benign schwannoma available for electron microscopic study demonstrated diffuse and abundant cytoplasmic intermediate filaments, and this tumor displayed diffuse and intense GFAP immunoreactivity. Two benign neurofibromas showed a more variable content of intermediate filaments ultrastructurally, and their GFAP immunoreactivity was variable. All five malignant nerve sheath tumors studied by electron microscopy displayed a variable complement of intermediate filaments; however, none of these tumors possessed GFAP immunoreactivity, suggesting that these intermediate filaments are either members of a different class of intermediate filaments or may perhaps represent "altered" GFAP not recognized by these antisera.
Cytoskeleton↗
Pheochromocytoma producing immunoreactive ACTH with Cushing's syndrome.
A 42-year-old female with clinical and endocrine indications of Cushing's syndrome, as well as periodic hypertension and increased urinary catecholamines and their metabolites, benefitted from removal of a pheochromocytoma. Adrenocortical hyperplasia was present. Electron microscopy showed catecholamine-type granules in the tumor cells; in addition, immunoreactive ACTH, leu-enkephalin, somatostatin, and serotonin were identified. Such studies were performed for the first time in this unusual condition.
Adrenal Gland Neoplasms↗
The biological implications of bronchial tumors.
Seventy-six consecutively resected primary pulmonary tumors were assessed first by routine light microscopy and subsequently by electron microscopy and immunohistochemical staining techniques to precisely identify features of differentiation. In 66% of the cases, this assessment provided information that modified or revised the histologic diagnosis provided by light microscopy alone. The following conclusions were reached: (1) The term "large cell undifferentiated carcinoma" has been applied to a heterogenous group of tumors, most of which have ultrastructural and immunohistochemical features of differentiation not identifiable by routine light microscopy. (2) Forty percent of the tumors previously called "large cell undifferentiated carcinoma" have predominantly neuroendocrine differentiation and appear to have a clinical course comparable to that of small cell neuroendocrine carcinoma. (3) The majority of pulmonary carcinomas (especially those previously called "poorly differentiated" or "undifferentiated") may simultaneously demonstrate more than one pattern of differentiation when studied by electron microscopy and immunohistochemistry. (4) The frequency of neuroendocrine neoplasms of the lung, as determined by these and previous studies, is considerably greater than suspected on the basis of light microscopic studies alone. These comprise a clinical and morphologic spectrum ranging from bronchial carcinoid to small cell carcinoma, all of which have immunohistochemically demonstrable hormone production, although paraneoplastic hormonal syndromes are manifested in only a small minority of cases.
Adenocarcinoma↗
Diagnosis of human tumors. Case 4: Neuroendocrine carcinoma of lung, intermediate size cell type.
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Aged↗
Diagnosis of human tumors. Case 5: Metastatic paraganglioma in lung (primary in left carotid body).
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Adult↗
Neuroendocrine cells and neuroendocrine neoplasms of the lung.
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APUD Cells↗
Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms.
The dispersed neuroendocrine (NE) system is represented in the bronchopulmonary tract by the solitary neuroendocrine cells and the neuroepithelial bodies (NEBs). Immunohistochemically, neuron-specific enolase, serotonin, bombesin, and calcitonin are demonstrable in both components, whereas leu-enkephalin is demonstrable only in solitary NE cells. The precise function of and interplay between these two components under physiologic and pathologic conditions are not entirely clear. Current indications are that NEBs act as intrapulmonary chemoreceptors sensitive to hypoxia and hypercapnia, whereas solitary NE cells may have a paracrine, regulatory function. Even less clear is the possible role of solitary NE cells and NEBs in the processes associated with intrauterine and neonatal pulmonary growth and maturation. Various experimental manipulations have resulted in proliferation of solitary NE cells and NEBs. Of particular interest is the apparently selective proliferative effect on NEBs shown by several nitroso compounds. Diethylnitrosamine administration to hamsters for several weeks results in an increase in the number of NEBs and an increase in the number of cells per NEB. These hyperplastic NEBs express the same immunoreactive hormones as their normal counterparts. However, when NEB cells from diethylnitrosamine-treated hamsters are cultured in vitro a notable proportion of the resulting endocrine cells express ACTH immunoreactivity. Interestingly, the neoplasms that eventually develop in these hamsters are not comprised of NE cells. Studies on human bronchi from specimens resected for various types of neoplasms and for bronchiectasis with and without associated chronic obstructive pulmonary disease have revealed frequent hyperplasias of solitary NE cells and NEBs. In about 10% of the specimens, dysplastic aggregates of solitary NE cells and NEBs are found. Unexpected "microcarcinoids" and tumorlets are also seen. The mildly and moderately hyperplastic solitary NE cells and NEBs tend to express the hormones indigenous to the bronchi, whereas in the severely hyperplastic and dysplastic cells, "ectopic" hormones may also be expressed; the latter include predominantly ACTH and vasoactive intestinal polypeptide. A distinct hyperplasia of NEBs has been found in the lungs from individuals living at altitudes ranging from 3400 to 4300 meters; these changes may represent an adaptive response to chronic hypoxia parallel to the hyperplastic carotid paraganglia that may be found in the same type of population. Bronchopulmonary NE neoplasms comprise a spectrum that includes typical carcinoids, well-differentiated NE carcinomas, and NE carcinomas of intermediate and small cell types. Typical carcinoids are predominantly central, display little if any pleomorphism, are richly granulated by electron microscopy, and by immunohistochemistry express predominantly, although not exclusively, hormones indigenous to their site of origin.(ABSTRACT TRUNCATED AT 400 WORDS)
APUD Cells↗
Selective emergence of differentiated chondrocytes during serum-free culture of cells derived from fetal rat calvaria.
Cells dispersed from the chondrocranial portions of fetal rat calvaria proliferated and performed specialized functions during primary culture in a chemically defined medium. Mature cultures were typified by multilayered clusters of redifferentiating cartilage cells. Flattened cells that lacked distinguishing features occupied areas between the clusters. Alkaline phosphate-enriched, ultrastructurally typical chondrocytes within the clusters were encased in a dense extracellular matrix that stained prominently for chondroitin sulfate proteoglycans. This matrix contained fibrils measuring 19 nm in diameter, which were associated with proteoglycan granules that preferentially bound ruthenium red. A progressive increase in the number of cells indicated the proliferation of certain elements in the primary culture. The cells in primary culture were biochemically as well as morphologically heterogeneous since they were found to synthesize type I and type II collagens. Homogeneous populations of redifferentiated chondrocytes were recovered as floating cells and were shown to express the chondrocyte phenotype in secondary culture. Subcultured cells synthesized type II collagen and its precursors almost exclusively and incorporated 35SO4 into proteoglycan monomer and aggregates to a greater degree than the cells in primary culture. The pattern of proteoglycan monomer and aggregate labeling resembled that of intact cartilage segments and bovine articular chondrocytes. Skin fibroblasts harvested from the same rat fetuses failed to proliferate when maintained under identical conditions. Hence, exogenous hormones, growth factors, and protein are not required for chondrocyte growth and maturation.
Animals↗
Synthesis of cartilage matrix by mammalian chondrocytes in vitro. I. Isolation, culture characteristics, and morphology.
We describe the isolation and the ultrastructural characteristics of adult bovine articular chondrocytes in vitro. Slices of bovine articular cartilage undergo sequential digestions with pronase and collagenase in order to release cells. Chondrocytes are plated at high density (1 x 10(5) cells/cm2) in culture dishes or roller bottles with Ham's F-12 medium, supplemented with 10% fetal bovine serum. Before culture, chondrocytes are freed of surrounding territorial matrix. Within the first few days of culture they re-establish a territorial matrix. As time progresses, chondrocytes synthesize both territorial and extraterritorial matrices. The matrices are rich in collagen fibrils and ruthenium red-positive proteoglycans. These features are most apparent in mass roller cultures in which aggregates of cells and matrix appear as long streaks and nodules. This morphology reveals an organization of chondrocytes and their matrices that is similar to that of the parent articular cartilage in vivo.
Animals↗
Synthesis of cartilage matrix by mammalian chondrocytes in vitro. II. Maintenance of collagen and proteoglycan phenotype.
The in vitro phenotype of bovine articular chondrocytes is described. Chondrocytes plated at high density in roller-bottle and dish cultures were maintained in vitro. The major matrix macromolecules, collagen and proteoglycan, synthesized by these cells were characterized during the course of the culture period. The chondrocytes synthesized mainly Type II collagen, which was found predominantly in the cell-associated matrix. The media contained a mixture of Type II and Type III collagens. Type I collagen was detectable in neither the medium nor the cell-associated matrix. The proteoglycan monomers found in media and cell-associated matrix had the same hydrodynamic sizes as monomers synthesized by cartilage slices or those extracted from adult articular cartilage. The majority of proteoglycans synthesized by the cells were found in high molecular weight aggregates which were readily recovered from the media and were extractable from cell-associated matrix with low ionic strength buffers. The results demonstrate the long-term in vitro phenotypic stability of the bovine articular chondrocytes. The advantages of the in vitro system as a model for studying the effects of external agents, such as drugs and vitamins, are discussed.
Animals↗
Neuroendocrine differentiation in basal cell carcinomas.
Ten consecutive cases of basal cell carcinomas were reviewed. Nine of these displayed the typical histology of basal cell carcinoma, the other case was composed of small spindle to ovoid cells with scant cytoplasm and a high mitotic rate, resembling an "oat cell" carcinoma. These were studied using the immunoperoxidase technique for tissue localization of calcitonin, insulin, glucagon, somatostatin, ACTH, gastrin and nerve growth factor. Three cases were negative for all hormones tested. Three cases were focally positive for a single hormone; one each for calcitonin, somatostatin, and ACTH. Two cases were focally positive for ACTH and somatostatin and two cases were focally positive for calcitonin, somatostatin and ACTH. None of the other hormones displayed activity. The positive staining was eliminated after absorption by the specific antigen. This immunohistochemical study illustrated neuroendocrine differentiation in basal cell carcinomas as has previously been suggested by the Grimelius stain and electron microscopy. Thus, as demonstrated in other epithelial neoplasms, basal cell carcinoma may also display neuroendocrine differentiation. This illustrates the potential multidirectional differentiation in neoplastic epithelial cells.
Adrenocorticotropic Hormone↗