Prediction of malignant behavior of pheochromocytomas and paragangliomas using immunohistochemical techniques

Pheochromocytomas and paragangliomas arise from the adrenal glands and extraadrenal paraganglia, respectively. Malignant behavior of these tumors is uncommon and is, in part, dependent on their sites of origin, such as extraadrenal location. Morphologic criteria for malignancy of pheochromocytoma and paragangliomas have not been clearly defined. In this study, to clarify the histologic features that distinguish the benign from malignant pheochromocytomas and paragangliomas, we examined metastatic and nonmetastatic tumors using immunohistochemical techniques. A total of eight cases, five pheochromocytomas from the adrenal glands (four benign and one malignant tumor) and three paragangliomas with invasion or metastasis, were studied. The markers used in this study were chromogranin A, synaptophysin, NCAM (CD56), SNAP25, neuron-specific enolase, S-100 protein, and MIB-1. Our results suggest that MIB-1 immunostaining is a useful adjunct marker to predict malignant behavior in these tumors.     

Epithelioid sarcoma. An immunohistochemical study

The immunohistochemical findings in 14 epithelioid sarcomas, neoplasms of uncertain histogenesis, indicate that they react with antibodies against cytokeratin, epithelial membrane antigen, and vimentin. All cases were nonreactive for leukocyte common antigen, myoglobin, and Factor VIII-related antigen. These results point to the fact that epithelioid sarcoma expresses phenotypic characteristics more often associated with epithelioid neoplasms, rather than the mesenchymal profile of most soft tissue sarcomas. One explanation for this observation is that epithelioid sarcoma is in fact a carcinoma originating in the deep soft tissues. On the other hand, the pluripotential mesoderm has a known embryonic capacity to differentiate into epithelium and, therefore, it is plausible that epithelioid sarcoma is a mesenchymally derived neoplasm. Aside from histogenetic considerations, epithelioid sarcoma may be confused with a number of other neoplastic and granulomatous processes. Differential immunohistochemical stains are useful in selected instances wherein light and electron microscopic findings are diagnostically equivocal.     

Mesenchymal chondrosarcoma. An immunohistochemical study

Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle-specific actin, cytokeratin, and epithelial membrane antigen, and the avidin-biotin-peroxidase complex (ABC) method. The small cells of mesenchymal chondrosarcoma failed to express S100 protein, whereas all components of the tumors (small cells, lacunar chondroblasts, and chondroid matrix) stained for Leu-7 antigen in six cases. Neuron-specific enolase was identified in the small cells of four cases and in the lacunar cells of seven. None contained desmin, actin, cytokeratin, epithelial membrane antigen, or synaptophysin. The immunophenotype of mesenchymal chondrosarcoma resembled that of embryonic cartilage and thus did not contradict the premise that this tumor was the neoplastic counterpart of fetal chondroid tissues. However, immunohistologic studies are not overly helpful in the differential diagnosis between mesenchymal chondrosarcoma and other small round cell lesions.     

Glomus tumours. An immunohistochemical study

The histological and immunohistochemical features of 20 glomus tumours (glomangiomas) were studied retrospectively in routinely processed material. The tumours came from 18 patients (9 women and 9 men, aged 25 to 80 years); two were recurring lesions. Twelve were classified as solid glomus tumours, eight as glomangiomas. Small nerve fibres were present in all except one. A variable number of mast cells were found in the stroma. The glomus tumour cells were negative when stained for Neuron-Specific Enolase, Glial Fibrillic Acidic Protein, S-100 Protein, Chromogranin, or with the Ulex Europaeus Lectin type 1. Conversely, all were found to be positive for Actin, Myosin, and Vimentin. Four exhibited an equivocal reaction for Desmin, the rest were negative. This immunohistochemical profile is in accordance with the findings of other investigators and can be helpful in differential diagnosis. It also shows the glomus cell to be related to smooth muscle cells and pericytes. The majority of these lesions are probably hamartomas, but a few may be true neoplasms.     

Capillary hemangioblastoma. An immunohistochemical study

Previous studies using immunohistochemical methods to determine the presence of glial fibrillary acidic protein (GFAP) and Factor VIII-related antigen (FVIIIR:Ag) in stromal cells of capillary hemangioblastomas have yielded conflicting results with respect to the possible astrocytic and endothelial origins of these cells. This study included Ulex europaeus I lectin (UEAI), a more sensitive marker of endothelial cells. Antibodies were also used as markers of pericytes and a variety of markers were employed to identify different populations of histiocytes. Results of this investigation indicate that FVIIIR:Ag and UEAI are limited only to endothelial cells, and that GFAP is present in entrapped astrocytes only. Positivity of stromal cells was found with some of the histiocytic markers, but the authors were unable to conclude that these cells have a histiocytic origin. It was concluded that currently there is no evidence that stromal cells are derived from endothelial, pericytic, or astrocytic cells-their origin remains uncertain.     

An immunohistochemical study of branchial cysts.

Twenty five specimens of branchial cyst from the same number of patients have been examined. On staining with haematoxylin and eosin a consistent finding was that the mural lymphoid follicles were always aligned with their mantle zones towards the luminal epithelium. With conventional staining lymphatic sinuses were noted in 17 of the specimens, but with immunohistochemical staining these structures were apparent in 23 cysts. Their frequent occurrence in branchial cysts supports the theory that these lesions are derived from epithelial inclusions in lymph nodes. Immunohistochemical techniques for a range of other markers, using polyclonal and monoclonal antisera, showed a distribution of lymphoid and non-lymphoid tissue elements, as seen in lymph nodes and, for example, palatine tonsils. The lining luminal epithelium also shared many features in common with the crypt epithelium of tonsils.     

动脉粥样硬化病变的免疫组织化学研究

Cellular composition of 31 cases of human atherosclerotic lesion was studied by immunohistochemical technique. Specimens were taken from the thoracic and abdominal aortas of necrosis. Four monoclonal antibodies were used to identify cell types. Monocytes/macrophages reacting with anti-Leu-M1 or anti-alpha-1-ACT were found in early lesions and some activated areas such as the peripheral region of bottom of atheromatous plagues of the advanced lesions. Some foamy cells also showed positive to alpha-1-ACT. In addition T lymphocytes reacting with anti-UCHL-1 were detected in the early lesions and some activated areas of advanced plaques, and both types of cells were more common in the early than in the advanced lesions. Other types of leukocytes were scanty in both early and advanced atheromatous lesions. In conclusion, the presence of a variable number of monocytes/macrophages and T lymphocytes in human atherosclerotic lesion may represent a cell-mediated immune response which may be very important in the initiation and progression of atherosclerotic lesion.     

An immunohistochemical study of feline myocardial fibrosis

The aim of the present study was to investigate the pathology of feline myocardial fibrosis. The hearts from 40 cats with myocardial fibrosis were compared with the hearts from 25 normal cats. Clinical data were available in 11 cases. Hearts with myocardial fibrosis were hypomotile and there were hyperechoic areas in the ventricular wall on echocardiography. The presence of myocardial fibrosis was correlated significantly with hypertrophy of the ventricles, atrial dilation and angiosclerosis. Immunohistochemical studies demonstrated that normal feline cardiomyocytes expressed matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, tissue inhibitor of matrix metalloproteinase (TIMP)-2 and transforming growth factor (TGF)-β2. Fibroblasts in normal hearts expressed only TIMP-2. In the hearts with myocardial fibrosis, expression of MMP-2, TIMP-3 and TGF-β2 by cardiomyocytes was significantly increased, but TIMP-2 expression was diminished. Fibroblasts in the affected hearts showed expression of MMP-14 in several cases. These findings suggest that a complex fibrotic remodelling of the feline myocardium occurs in this disease and that cardiomyocytes are involved in this process.     

A comparative immunohistochemical study of spontaneous and chemically induced pheochromocytomas in B6C3F1 mice

Spontaneously occurring and chemically induced pheochromocytomas are rare in mice. That the mouse pheochromocytoma is a more appropriate animal model than that of the rat for study of human medullary adrenal tumors has been suggested. The expression of phenylethanolamine-N-methyltransferase (PNMT), the enzyme responsible for production of epinephrine from norepinephrine, is common to both mouse and human pheochromocytomas. This investigation assessed the expression of the immunohistochemical markers PNMT, tyrosine hydroxylase (TH), and chromogranin A (CGA) in spontaneously occurring and chemically induced pheochromocytomas in the B6C3F1 mouse. Spontaneous tumors were derived from control animals from 10 different studies and the pheochromocytomas from treated groups from 4 different studies. All tumors were positive for maximal TH expression. A highly significant difference in PNMT expression (p<0.01) occurred between spontaneously occurring pheochromocytomas classified as benign or “malignant” by the criteria of toxicologic pathology. Chemically induced tumors showed intermediate PNMT staining. A marked reduction in CGA expression occurred in pheochromocytomas induced by technical grade pentachlorophenol, compared to the other three chemicals and the spontaneously occurring tumors. These findings suggest that immunohistochemistry is a reliable tool in investigating the functional capabilities of pheochromocytomas in mice. PNMT expression is a tightly regulated component of the chromaffin cell phenotype and appears to be readily lost in mouse pheochromocytomas, particularly those with aggressive characteristics.     

An immunohistochemical study of canine nasal aspergillosis

In this study, histochemistry and immunohistochemistry were used to characterize the phenotype and distribution of leucocytes in the distal nasal mucosa of 15 dogs with nasal aspergillosis. The most consistent histopathological finding was a severe, predominantly lymphoplasmacytic, inflammatory infiltration of the lamina propria. Fungal hyphae were not observed to invade the mucosa but were found at the mucosal surface and within material collected from the nasal cavity. The main immunohistochemical findings were (1) a predominance of IgG(+) plasma cells over IgA(+) and IgM(+) plasma cells, (2) significant numbers of macrophages and dendritic cells expressing MHC class II molecules, (3) macrophages and neutrophils expressing L1 antigen and (4) a mixture of CD4(+) and CD8(+) T cells. These findings are consistent with a dominant Th1-regulated cell-mediated immune response. The nature of the inflammatory infiltrate and the lack of invasiveness of the mucosa by the fungus, together with the clinical course of the disease and the apparent immunocompetence of the affected dogs, suggest that canine nasal aspergillosis resembles the chronic erosive non-invasive fungal sinusitis described in human patients.     

Parachordoma: An ultrastructural and immunohistochemical study

A case of parachordoma of the left calf in a 19-year-old Chinese female is reported. The tumour showed multinodular growth pattern and consisted of round or oval tumour cells with abundant eosinophilic cytoplasm and myxoid matrix. Tumour cells formed small nests and sometimes showed concentric arrangement. Physaliferous-like cells and undifferentiated spindle cells were occasionally observed among the cell nests. The myxoid matrix was positive for high-iron diamine stain, indicating the presence of chondroitin 4- and 6- sulphates and keratan sulphate. Ultrastructurally, well-developed rough endoplasmic reticulum, abundant intermediate filaments, microvillous cytoplasmic processes, pinocytic vesicles, and desmosome-like junctional structures were found. Tumour cells were positive for S-100 protein and vimentin, but negative for cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, and desmin. These results are consistent with the definition of parachordoma as a soft tissue neoplasm consisting of cells with histology and ultrastructure similar to those of chordoma cells but with immunohistochemistry similar to that of chondroid tumour cells.     

Urinary bladder paragangliomas. An immunohistochemical study

The immunohistochemical characteristics of three cases of urinary bladder paragangliomas are presented. These are compared with similar studies on paragangliomas from other anatomic sites and the clinical and pathologic implications are discussed.     

An immunohistochemical study of Warthin-Finkeldey cells in measles

An autopsy case of an 18 month old male infant with measles infection Is reported. An autopsy revealed generalized lym-phadenopathy, splenomegaly and hyperplastic thymus. Histologically, there were many Warthin-Finkeldey cells (WFC) in hyperplastic lymphoid tissues. Although viral particles and inclusions were not detected electronmicroscopicaliy, the infection of measles virus was detected in WFC by immunofluorescent technique using anti-measles antibody. Warthin-Finkeldey cells were morphologically and immu-nohistochemically divided into two groups. The first type was WFC appearing in the germinal centers of lymphoid tissue, revealing many large nuclei and B cell markers. The second type was WFC appearing in the interfollicular areas and thymus, showing many small hyperchromatlc nuclei and T cell markers. The data indicate that there might be a morphologic and immunophenotypic heterogeneity in WFC.     

Chordoma. An immunohistochemical study of 20 cases

Twenty chordomas from 20 patients, including 17 nonchondroid and three chondroid types, were studied with a variety of antibodies directed against cytokeratin (AE-1/3), epithelial membrane antigen, carcinoembryonic antigen, S100 protein, vimentin, alpha 1-antichymotrypsin, and lysozyme. All 17 nonchondroid chordomas stained for cytokeratin, and most (16) stained for epithelial membrane antigen. In contrast, two chondroid chordomas failed to stain for either cytokeratin or epithelial membrane antigen, while one of them did stain for both antigens. Sixteen of the 20 chordomas (80%) stained for S100 protein, including all three chondroid chordomas. Vimentin was found in six (30%), and alpha 1-antichymotrypsin in 16 chordomas (80%). Carcinoembryonic antigen and lysozyme were each found in two specimens (10%). While these findings basically agree with the immunohistochemical studies of other investigators, there are a few discrepancies. Most significant is the lack of epithelial markers in two of three chondroid chordomas located at the base of the skull. Possible reasons for the discrepancies are discussed.     

An ultrastructural and immunohistochemical study of central neurocytoma

A case of central neurocytoma was studied by electron microscopic and immunohistochemical methods. Immunohistochemical examinations showed the tumor cells to be positive for neuron-specific enolase, sporadically positive for synaptophysin, and negative for glial fibrillary acidic protein. The Ki-67 (MIB-1) positive index value for the tumor cells was a low 1.5%. Ultrastructurally, thin cytoplasmic processes of tumor cells showed differentiation to neuronal cells containing parallel bundles of microtubules and abortive synapses with dense core vesicles and/or clear vesicles. Microvessels composed of endothelial cells without fenestrations and tight junctions in the endothelial clefts appeared in fibrillary stromas as revealed by light microscopy. Neurosecretory granules in thin cell processes may have been secreted around microvessels.     

Meningiomas. An immunohistochemical study of 50 cases

Fifty formalin-fixed, paraffin-embedded meningiomas were studied with a panel of ten antibodies directed against epithelial antigens, intermediate filaments, and neuroectodermal antigens. Twenty-five (50%) of these were stained with monoclonal antibodies (MoAb) to epithelial membrane antigen (EMA), 12 (24%) with keratin antibodies, 9 (18%) for vimentin, and 4 (8%) for S100 protein. Monoclonal antibodies to Leu-7, desmin, neurofilament 200 kDa, and glial fibrillary acidic protein (GFAP) all failed to stain any of the 50 neoplasms. Overall, 34 (68%) meningiomas stained with one or more antibodies. Sixteen (32%) failed to stain at all. The dual epithelial and mesenchymal nature of meningiomas is supported in this study. Applications to diagnostic surgical pathology and histogenetic implications are discussed.     

Prostatic origin of tumors. An immunohistochemical study

An immunoperoxidase technic was used to localize prostatic acid phosphatase in a variety of primary and metastatic neoplasms. The aim was to explore the histogenesis of tumors affecting the prostate gland and to demonstrate the prostatic origin of metastases in various sites. A highly specific antiserum to prostatic acid phosphatase was raised in rabbits, and the peroxidase-antiperoxidase procedure was carried out on formalin-fixed paraffin-embedded routine pathology material. All specimens from the 37 cases of known primary and metastatic prostatic carcinomas stained positively for prostatic acid phosphatase, regardless of their histologic differentiation. None of the specimens from the 44 cases of proven nonprostatic primary and metastatic tumors stained positively for prostatic specific acid phosphatase. The data suggest that demonstration of prostatic acid phosphatase by the immunoperoxidase technic is a practical, sensitive, and specific test for the prostatic origin of an otherwise unclassifiable primary or metastatic neoplasm.     

Nasal glioma: An immunohistochemical and ultrastructural study

A case of a 14 month old Japanese female infant presenting with nasal glioma Is reported. The tumor had been noticed at the nasal radix since birth and had slowly and progressively enlarged. There was no communication between the tumor and the cranial cavity on radiological examination. The tumor was macroscopically anchored to the nasal septum by a fibrous stalk, and histologically consisted of nests or trabeculae of either polygonal or spindle cells with plump eosinophilic cytoplasm and oval nuclei, separated by vascular-rich connective tissue intermingled with multinu-cleated giant cells. These tumor cells were immunohisto-chemically positive for glial fibrillary acidic protein as well as for S-100 protein and vimentin. An electron microscopic examination revealed collagen fibers and basal lamina between the tumor cells and the fibroblasts. Tumor cells possessed abundant intermediate filaments, which showed occasional Rosenthal fiber-like structures, in their cytoplasm and processes. A few oligodendrocytes and cilia of 9 micro-tubule doublets either with or without 2 central microtubules were also noted. These clinicopathological findings suggested that this tumor was once an encephalo(meningo)cele, which probably degenerated as a result of the loss of intracranial communication and then appeared to be isolated from the intracranial tissue.