Extra-adrenal paraganglioma of the median nerve.

An extra-adrenal paraganglioma is an uncommon tumour that arises from the paraganglia associated with the autonomous nervous system. A paraganglioma arising in the sensory-somatic nervous system is extremely rare and clinically is easily confused with other neurogenic tumours. We describe a paraganglioma that arose in the median nerve of a 22-year-old woman.

Extra-adrenal retroperitoneal paraganglioma in a dog.

An extra-adrenal retroperitoneal paraganglioma was observed in a 10.5-year-old male Boxer dog. Additionally, the dog had an aortic base tumor, multiple thyroid adenomas, multiple testicular interstitial cell tumors, bilateral nodular adrenal cortical hyperplasia, and parathyroid gland hyperplasia. The hypothesis that the retroperitoneal mass represents a primary extra-adrenal paraganglioma rather than metastatic mass from the aortic body tumor is considered. Either primary or metastatic extra-adrenal retroperitoneal paragangliomas are rarely reported in dogs.

Pigmented paraganglioma of the kidney: a case report.

Paragangliomas are rare neoplasms arising from undifferentiated cells of the primitive neural crest. We report a case of a 57-year-old patient with renal pigmented paraganglioma that was an incidental finding. Histopathological examination showed typical morphology of paraganglioma, as well as the unusual feature of large amounts of pigment in the cytoplasm of the tumor cells which was confirmed by bleached Fontana-Masson. Electron microscopy showed abundant, pleomorphic electron-dense granules consistent with neuromelanin. The tumor cells were positive for CD56 and chromogranin A, negative for HMB-45. The unique morphologic appearance represents divergent differentiation from neural crest. To our knowledge, the present case represents the first example of pigmented paraganglioma of the kidney. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2017147293711495.

Ultrastructural characteristics of chemodectomas.

We present results of morphological study of chemodectoma samples obtained during surgery. Specific ultrastructural features and protein-synthesizing and proliferative activity of light and dark cells were demonstrated using data of electron radioautography.

[Electron-radioautographic study of parasympathetic paragangliomas (chemodectomas) of the neck]. / élektronno-radiograficheskoeissledovanie parasimpaticheskikh paragangliom (khemodectom) shei.

Chemodectomas, after the surgery, were studied in 7 patients. Morphologically their malignancy is proven on the basis of pronounced cell polymorphism, atypia, invasion of tumour cells through the vessel wall into their lumen. Besides rare mitoses, proliferative (DNA synthesis) and protein synthetic (RNA synthesis) activity in clear and dark cells was not observed in the presence of intensive biosynthetic processes in the stroma cells.

[Histological variants of parasympathetic paragangliomas (chemodectomas) of the neck and morphological variants of their malignancy]. / Gistologicheskie varianty parasimpaticheskikh paragangliom (khemodektom) shei i morfologicheskie kriterii ikh zlokachestvennosti.

Histotopograms of 28 chemodectomas have been studied. Principal microscopic features of malignancy are as follows: structural atypia (complete in solid or fibrous variants) or partial (alveolar chemodectoma) loss of alveolarity as the most important sign of organotypia; another sign of malignancy is cell cataplasia (cell and nuclear polymorphism, change in nuclear-cytoplasmic relationship in the direction of its increase, nuclear hyperchromatism, appearance of large ungly hyperploid nuclei, mitotic activity of tumour cells in one case. Incomplete angiogenesis characteristic for malignant tumours was also detected. Invasive growth in the majority of chemodectomas in the form of partial growth through the walls of great vessels and ubiquitous growth through the walls of small vessels were present in most chemodectomas. Thus, there is a basis to claim that the chemodectomas studied are malignant tumours although they are characterized by a slow (years) growth and slow progression.

Pulmonary meningothelial-like nodules: a genotypic comparison with meningiomas.

BACKGROUND: Minute pulmonary meningothelial-like nodules (MPMNs) are incidental interstitial pulmonary nodules. They share histologic, ultrastructural, and immunohistochemical features with meningiomas (MGs). DESIGN: Sixteen cases yielding 33 separate MPMNs and 10 cases of benign MG were studied. Immunohistochemical studies and mutational analyses were performed on microdissected tissue using 20 polymorphic microsatellite markers targeting 11 genomic regions in an effort to identify genetic similarities of MPMN and MG. RESULTS: A total of 96.6% of MPMNs stained positive for vimentin, 33.3% for epithelial membrane antigen, 3% for S-100, and all were negative for cytokeratin and synaptophysin. Loss of heterozygosity (LOH) was identified in 25% of single MPMN affecting 3 genomic loci. No solitary MPMN had more than 1 LOH event. Multiple LOHs were seen only in MPMN-omatosis syndrome, where 33.3% of MPMNs showed LOH affecting 7 genomic loci. MG showed the highest frequency of LOH with major events seen at 22q (60%), 14q (42.8%), and 1p (44.4%) that were not shared by MPMN. CONCLUSION: Isolated MPMN lacks mutational damage, consistent with a reactive origin. MPMN-omatosis syndrome might represent the transition between a reactive and neoplastic proliferation. MPMNs are different from MG based on the major molecular genetic events seen in their formation and progression.

Diagnostic usefulness of sustentacular cells in paragangliomas: immunocytochemical and ultrastructural investigation.

Neuroendocrine tumors may derive either from neuroectoderm or endoderm. Both may present with a similar histologic pattern known as "Zellballen" regardless of their histogenetic origin, making it difficult to separate the two different histogenetic entities in certain cases. To evaluate the usefulness of sustentacular cells in the recognition of tumors of paraganglionic origin, the authors analyzed immunohistochemical and ultrastructural characteristics of 25 paragangliomas and 19 pulmonary and 10 small intestinal carcinoids. Sustentacular cells with characteristic dendritic features, strong immunoreactivity for S-100 protein, and agranular cytoplasm by electron microscopy were found consistently in the paragangliomas and not found in typical carcinoid tumors, except for four examples of spindle cell carcinoid of the lung. The presence of sustentacular cells in tumors with "Zellballen" pattern therefore denotes paraganglionic origin.

Paraganglioma: an unusual tumour of the parathyroid gland.

A case of paraganglioma arising within a parathyroid gland is reported. The lesion was an incidental finding in a block dissection of neck performed for squamous carcinoma of the pharynx. A well-circumscribed lesion, exhibiting the characteristic pathological features of a paraganglioma, was embedded within the right inferior parathyroid gland. Due to its location, the chief histological differential diagnosis was an unusual variant of parathyroid adenoma. Immunohistochemistry and electron microscopy assisted in reaching a diagnosis. This, as far as we are aware, is the first reported case of a paraganglioma of the parathyroid gland.

Melanotic paraganglioma of the posterior mediastinum.

A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour recurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a "zellballen" pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.

Diagnostic immunoelectron microscopy in surgical pathology: assessment of various tissue fixation and processing protocols.

We have investigated various tissue fixation and embedding protocols in an effort to allow expanded use of immunoelectron microscopy in diagnostic surgical pathology. A sample of normal human small bowel mucosa was processed using seven different methods for subsequent postembedding localization of chromogranin A. In addition, several archival cases of neuroendocrine tumors previously fixed and routinely embedded for electron microscopy, stored in formalin, or snap-frozen were retrieved and variously processed for chromogranin A localization at the ultrastructural level. Precise localization of chromogranin A in dense core granules was achieved with protein A-gold on sections from all of the processing methods. The methods included retrieval into mild fixative of previously formalin-fixed or snap-frozen tissues followed by embedding in Lowicryl K4M (Polysciences Ltd., Eppelheim, Germany). Thus, tissue processed without foresight of the need for immunoelectron microscopic localization can be successfully used. Since embedding of tissues in Lowicryl K4M has been shown to preserve a variety of antigens, it may prove to be a superior resin for use in diagnostic immunoelectron microscopy.

Aorticopulmonary paraganglioma (aortic body tumor): report of a case.

A case of aorticopulmonary paraganglioma in a 57-year-old man is described. The tumor comprised nests of uniform cells in a fibrovascular stroma. Electron microscopy revealed abundant neurosecretory granules, and S-100 protein staining demonstrated scattered sustentacular cells at the periphery of typical zellballen. The findings in this case correlated with those of studies on the prognosis for extraadrenal paragangliomas.

So-called minute chemodectoma of the lung. An electron microscopic and immunohistochemical study.

So-called minute pulmonary chemodectoma is a curious, small lung tumour found mainly in women. The nature and origin of the proliferating cells are still obscure. In the first report on the tumour, the component cells were described as resembling chemoreceptor cells and the tumour was named chemodectoma. However, electron microscopic studies of the tumour have revealed no evidence of neuronal characteristics and have shown a close resemblance to meningothelial cells. In this study, the electron microscopic findings were similar to those previously reported but in one of the two cases, tumour cells were filled with abundant cytofilaments, giving them an occasional dense, patch-like appearance. Immunostaining for myosin and vimentin was positive in all tumour cells, but epithelial membrane antigen staining was not seen. These findings indicate that the tumour might have its origin from muscle cells.

[Morphology and histogenesis of paraganglioma]. / Morfologiia i gistogenez paragangliomy.

Histological and ultrastructural studies were performed to examine 6 paragangliomas of various sites: carotid glomus, aortic body, sympathetic chain, and stomach. Five of the tumors in question had a histological structure typical of a paraganglioma. The gastric tumor was distinguished by being similar to a pheochromocytoma. With regard to the degree of infiltrative growth, the paragangliomas of the sympathetic chain and stomach were regarded as malignant. The ultrastructures of the paragangliomas examined were found to be of the same type. In all the neoplasms, tumor cells had signs of neuroendocrine and neurogenous differentiations that were characteristic of the ultrastructural organization of postganglionic neurons in the autonomic nervous system. The neurogenous differentiation was evidenced by cytoplasmic portions that are structurally similar to rough-surface endoplasmic reticulum, which is pertaining to Nissl's bodies; neurofilaments that form concentric structures containing neuroendocrine granules such as fibrous or Pick's bodies; intracytoplasmic cilia; specialized cytoplasmic processes of two types: axons and dendrites; partially reduced intercellular contacts, such as axosomatic and axodendritic synapses; sustentacular cells (sustenocytes). In the neoplasms evaluated as malignant, the neurogenous differential signs were more pronounced by reducing the number of neurosecretory granules, which might, apparently, serve as an ultrastructural criterion for establishing the degree of paraganglioma malignancy.

[Clinico-morphologic and electron microscopic characteristics of chemodectoma of the neck]. / Kliniko-morfologicheskaia i élektronno-mikroskopicheskaia kharakteristika khemodektomy shei.

Chemodectoma of the neck is one of the rare tumors occurring in man. The paper presents an observation of cervical chemodectoma found in a patient aged 31 years. For preoperative differential diagnosis, carotid angiography, ultrasound and radioisotopic examinations were used, which allowed the tumor located at the bifurcation of the left carotid artery to be diagnosed. The material taken during the surgery was histologically and electron microscopically examined to verify benign chemodectoma (an alveolar variant).

Minute pulmonary meningothelial-like nodules. A clinicopathologic study of so-called minute pulmonary chemodectoma.

The clinicopathologic features of 23 so-called minute pulmonary chemodectomas from nine patients are presented. Eight patients were women and one was a man; age range was 34-75 years (mean, 61). Two specimens were surgical resections and seven were autopsies (incidence, one per 60 autopsies). There was no association with a specific disease process or pathologic condition. Grossly, the lesions were 1-3 mm, tan to yellow, pleural or parenchymal nodules. Six of nine cases had multiple lesions; upper lobes were more often involved. Microscopically, characteristic cell nests expanded alveolar septa. Larger lesions were connected by intervening collagen, often imparting a stellate configuration. Smaller lesions had closely apposed nests with mildly thickened alveolar septa. The nodules were strongly reactive for epithelial membrane antigen (12 of 14) and vimentin (10 of 14), and were uniformly negative for cytokeratin, S-100, neuron-specific enolase, and actin. Ultrastructurally, complex interdigitating cell processes were connected by desmosomes. Occasional cytoplasmic filaments were seen. These nodules lack neuroendocrine features, differ from mesothelium, and strongly resemble meningothelial cells. A more accurate term for these lesions is minute meningothelial-like nodules. Their relationship to larger, solitary pulmonary meningiomas is unclear.

Extraadrenal paragangliomas. An immunocytochemical and ultrastructural report.

Although the majority of extraadrenal paragangliomas are nonfunctional, some of these tumors are associated with hormone production and clinical symptoms, notably hypertension. The authors have investigated 22 paragangliomas, five of which were diagnosed as clinically functional in a light microscopic immunocytochemical and electron microscopic study (nine cases). Histologically, all the paragangliomas exhibited similar features, with a "Zellballen" pattern of polygonal cells. All 22 cases were strongly immunoreactive to protein gene product 9.5 (PGP 9.5) antisera and moderately reactive to antineuron-specific enolase (NSE) sera. Ten cases (five functional) were focally immunoreactive to antichromogranin sera. Seven cases (four functional) were immunoreactive to neuropeptide Y and enkephalin antisera, and six (five functional) to tyrosine hydroxylase antisera. The clinically functional tumors expressed at least two of the antigens, enkephalin, neuropeptide Y, or tyrosine hydroxylase, whereas none of the 17 nonfunctional possessed more than one of these. Electron microscopic study revealed cells from all the nine cases studied to contain secretory granules. Granule sizes ranged from 100 to 280 nm and the morphologic examination of the secretory granules generally showed a dense core with a membrane-bound halo of variable size. Secretory granules were observed in the five functional cases and these were larger (220-280 nm) than those seen in the nonfunctional tumor cells (100-180 nm). Also, tumor cells from the functional cases contained numerous dilated mitochondrial profiles.

[Ultrastructure of chemodectomas of the neck]. / Ul'trastruktura khemodektom shei.

Two types of cells (dark and clear) with secretory granules in the cytoplasm were identified in these tumors. No specific ultrastructural features that would distinguish tumors differing in the degree of maturity were noted in the cells.

Aortic body tumour with adjacent ectopic thyroid tissue in a dog.

A 12-year-old neutered male Husky dog had a neoplasm at the base of the heart which did not invade surrounding tissues. Microscopically, the neoplasm was composed of nests and sheets of polyhedral cells subdivided into lobules by trabeculae of fine fibrovascular stroma. Adjacent to the neoplasm was a rim of ectopic thyroid tissue that appeared histologically normal. The possible differential diagnoses for the neoplasm were aortic body tumour, ectopic thyroid tumour and ectopic parathyroid tumour; the ultrastructural characteristics revealed it to be an aortic body tumour.