Oncocytic lesions of the neuroendocrine system.

This paper reviews the pathologic features of lesions which are oncocytic and involve classic endocrine organs. The history of the oncocytic cell, its morphologic and ultrastructural features, and important immunohistochemical findings are reviewed. Oncocytic proliferations including non-neoplastic and neoplastic of the thyroid, parathyroid, adrenal (both cortex and medulla), and pituitary are described. Their clinical relevance, functional capacity and capability, and where appropriate, prognostic implications are discussed. Important and relevant molecular biological information is included where appropriate.

A rare, human prostate oncocyte cell originates from the prostatic carcinoma (DU145) cell line.

DU145 human prostate carcinoma cells are typically poorly differentiated and contain only scantily distributed organelles. However, among numerous tumor cells randomly examined by electron microscopy out of in vitro cultivation, a peculiar, rare oncocyte-like cell type has been observed whose nucleus appears to be of small dimension and with a cytoplasm almost entirely filled with often distorted mitochondria. A few small, dispersed lysosomal bodies, small cisterns of the endoplasmic reticulum and a few glycogen patches can be found among highly osmiophilic contrasted, cytosolic spaces filled by innumerable ribonucleoproteins. The excessive population of mitochondria may have arisen from a more populated tumor cell type wherein the altered mitochondria are found to appear burgeoning into a spherical-like size progeny crowding the tumor cells. Literature cited between 1950 and the present suggests that this rare, oncocytic, benign prostatic tumor cell type is likely appear epigenetically, stemming from an original secretory cell, which is confirmed by the origin of the cell line originally maintained as cell line out of a brain metastatic, adenocarcinoma niche.

[Connection of magnetic antisense probe with SK-Br-3 oncocyte mRNA nucleotide detected by high resolution atomic force microscope].

The present paper is aimed to detect superparamagnetic iron oxide labeled c-erbB2 oncogene antisense oligonucleotide probe (magnetic antisense probe) connected with SK-Br-3 oncocyte mRNA nucleotide by high resolution atomic force microscope (AFM). We transfected SK-Br-3 oncocyte with magnetic antisense probe, then observed the cells by AFM with high resolution and detected protein expression and magnetic resonance imagine (MRI). The high resolution AFM clearly showed the connection of the oligonucleotide remote end of magnetic antisense probe with the mRNA nucleotide of oncocyte. The expression of e-erbB2 protein in SK-Br3 cells were highly inhibited by using magnetic antisense probe. We then obtained the lowest signal to noise ratio (SNR) of SK-Br-3 oncocyte transfected with magnetic antisense probe by MRI (P<0.05). These experiments demonstrated that the high resolution AFM could be used to show the binding of magnetic antisense probe and SK-Br-3 mRNA of tumor cell nuclear.

Responses of parathyroid gland, C cells, and plasma calcium and inorganic phosphate levels in rat to sub-lethal heroin administration.

In order to record the effects of heroin on plasma calcium (Ca) and inorganic phosphate (Pi) levels as well as parathyroid gland and C cells, two sub-lethal doses (0.50 LD50 and 0.75 LD50) of the drug were administered intramuscularly in Rattus norvegicus for 30 days. Plasma Ca level of control rats ranged between 9.53 +/- 0.32 - 9.88 +/- 0.22 mg 100 ml(-1) while plasma Pi concentration fluctuated between 4.55 +/- 0.18 - 4.71 +/- 0.24 mg 100 ml(-1). Sub-lethal heroin administration induced progressive increase in plasma Ca level during the first seven days (p < 0.001), thereafter the level declined on day 15 and 30. However plasma Pi level of the heroin-treated rats registered increase with the peak value (p < 0.001) on day 30. The treatment elicited degenerative changes in parathyroid gland as evident by cytoplamic vacuolization, presence of more pycnotic nuclei and occurrence of patchy areas among the chief cells. Degenerative changes were also noticed in cristae of mitochondria, Golgi complex and endoplasmic reticulum. There was decrease in chromatin material in the nucleus and loss of hormone granules in the cytoplasm. Oxyphil cells of the heroin-treated rat depicted dilation of endoplasmic reticulum and damaged cristae. Sub-lethal heroin administration in the rat for 30 days induced dilation in endoplasmic reticulum and loss of secretory granules in C cells.

Application of atomic force microscopy in morphological observation of antisense probe labeled with magnetism.

PURPOSE: To explore the possibility of the c-erbB2 oncogene antisense probe labeled with superparamagnetic iron oxide (SPIO) nanoparticles as a target contrast agent for magnetic resonance (MR) imaging whose morphology was observed with atomic force microscopy (AFM), and its efficiency was examined by MR imaging. METHODS: The c-erbB2 oncogene antisense probe labeled with SPIO was synthesized by a chemical cross-linking approach. Its morphology was observed with AFM. RESULTS: The chemical constitution of c-erbB2 oncogene antisense probes can be observed with AFM. The molecular structure of probes is easily visualized under AFM. Probes with diameters of 25-40 nm are in order, follow uniformity and the arrangement rule, can be separated from each other, and appear as cubes with a rugged surface morphology. Strong, low signals of the probes in transfected cells were observed by MR cellular imaging. CONCLUSIONS: AFM is ideal for morphological observation and for analyzing the molecular structure of synthesized c-erbB2 oncogene antisense probes.

Papillary cystadenocarcinomas of salivary glands with oncocytic epithelial lining: report of 2 cases.

Papillary cystadenocarcinoma involving the salivary glands is rare, and there are only about 13 case reports and a single large series of 57 cases in the literature. We report 2 cases of this rare entity with emphasis on the diagnostic histomorphological features. The cases are also distinctive, in that they have an epithelial lining, which is oncocytic throughout. One of our cases was detected in an 8-year-old male child, which is itself a rarity.

Relationship between morphological development and sex hormone receptor expression of mammary glands with age in male rats.

The aim of this study is to investigate the changes with age on morphology and sex hormone receptor expression in the mammary glands of male Sprague-Dawley rats, focusing on male-specific cells, "oxyphilic cells", observed after sexual maturity. The mammary glands of male rats at 14, 21, 35, 50, 75 and 100 days old were examined by gross observation, microscopic observation using whole mount specimens, histological and immunohistochemical sections. Grossly, mammary glands showed brown color at 50-100 days old. In whole mount specimens, terminal end buds (TEBs) were observed at 14-50 days old and the number of TEBs was highest at 35 days old. Histologically, the male mammary glands contained small epithelial cells with scanty cytoplasm at 14-35 days old while ductal and lobular epithelial cells were changed into oxyphilic cells with abundant cytoplasm at 50-100 days old. Immunohistochemicaly, androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PgR) expressions were found in both mammary glands found at a young age and oxyphilic cells. In oxyphilic cells, AR expression was dominant compared to ER and PgR expressions and increased with age. From these results, the development at 50-100 days old might be strongly related to AR. Ultrastructural observation of oxyphilic cells confirmed a number of lipid droplets, deformed and/or enlarged mitochondria, lysosomes and peroxisomes in their cytoplasm.

Multifocal nodular oncocytic hyperplasia in parotid gland: a case report.

BACKGROUND: Multifocal nodular oncocytic hyperplasia (MNOH) is a rare lesion of the parotid gland. Fine needle aspiration cytology (FNAC) in MNOH has not been described previously to the best of our knowledge. CASE: A 55-year-old woman presented with a lump at the left angle of her mouth for 2 months. Local examination revealed a hard, nontender parotid mass. FNAC revealed clusters as well as discretely lying oncocytic cells. cells at places showed moderate nuclear pleomorphism. The features were consistent with a diagnosis of oncocytic neoplasm neoplasm; however, because of pleomorphism, a suspicion of carcinoma was offered. The patient underwent superficial parotidectomy, and histopathology examination revealed it to be multifocal nodular oncocytic hyperplasia. CONCLUSION: MNOH is a rare nonneoplastic salivary gland lesion and should be considered in the differential diagnosis of oncocytic neoplasm on FNAC.

Rectal adenocarcinoma with oncocytic features: possible relationship with preoperative chemoradiotherapy.

BACKGROUND: The introduction of preoperative chemoradiation into the treatment protocol of rectal adenocarcinomas has affected the microscopical morphology in subsequent resection specimens. The constellation of histopathological changes is varied and well documented. AIM: To describe oncocytic change in rectal cancers that have been treated with chemoradiation before surgery. METHODS: 7 of 54 patients with rectal cancer were identified with a history of chemoradiation, specifically directed to the rectal tumours in fractions of 4500-5000 cGy of radiation and 5-fluorouracil. The rectal tumours in five of these seven patients were composed of oncocytes that constituted 30-80% of the cancers. The patients were three men and two women aged 65-73 years, all with T3 N0 tumours. The intervals between chemoradiation and resection varied from 3 to 12 weeks. RESULTS: The tumour cells conformed to oncocytes morphologically (large size with abundant, granular eosinophilic cytoplasm, vesicular nuclei and prominent acidophilic nucleoli), immunohistochemically (positive for carcinoembryonic antigen, cytokeratin 20 and caudal type homeo box transcription factor 2, but negative for both chromogranin and synaptophysin) and ultrastructurally (large cells showing tight junctions, cytoplasmic engorgement by mitochondria and absence of neurosecretory granules). CONCLUSIONS: The changes in these cells differ from those described previously in endocrine cells encountered in pretreated rectal cancers. Oncocytic change in this particular clinical context occurs as a reflection of cytotoxic damage or cellular hypoxia induced by chemoradiation resulting in degeneration of the cell and the oncocytic phenotype. Oncocytic change may be an under-recognised histopathological change in rectal cancers receiving preoperative chemoradiation.

Chromophobe renal cell carcinoma with microcystic and adenomatous arrangement and pigmentation--a diagnostic pitfall. Morphological, immunohistochemical, ultrastructural and molecular genetic report of 20 cases.

We present clinical, morphological, immunohistochemical, ultrastructural and molecular genetic features of 20 cases of a peculiar form of chromophobe renal cell carcinoma (CRCC) with morphology differing from that of conventional CRCC. Microscopically, the typical features of the tumors were microcystic arrangement and formation of adenomatous structures. Microcystic areas were composed of smaller eosinophilic and bigger pale cells having cytological appearance typical of conventional CRCC. Cytological features of the adenomatous structures were mostly different from those of conventional CRCC. They had a typical columnar arrangement with nuclei positioned at the base of the glandular structures and a small amount of a deeply eosinophilic cytoplasm often endowed with brush border facing the lumen of the glands. In addition, all the tumors showed a brown pigmentation. The pigmentation was located mostly extracellularly, where it formed pools of heavy deposits. Microscopic calcifications present in all cases formed psammoma bodies or else the calcifications were more extensive and amorphous in shape. Ultrastructurally, the cells showed features characteristic of CRCC: typical cytoplasmic vesicles were 100-700 nm in size and mitochondria had tubulovesicular, lamellar or circular cristae. Some tumor cells contained dark, variously sized electron-dense pigment granules. Neither melanosomes nor membrane-bound neurosecretory granules were seen. Using fluorescence in-situ hybridization probes for chromosomes 1, 2, 6, 10, 13, 17 and 21, the tumors revealed massive loss of tested chromosomes typical for conventional CRCC. Monosomy of chromosomes 1, 2, 6, 10, 13 and 21 was found in 100, 36, 91, 82, 82, 82 and 64% of cases, respectively. None of the cases showed mutation of exons 9, 11, 13 and 17 of the c-kit gene. The important feature of pigmented microcystic chromophobe renal cell carcinoma is a relatively benign biological behavior and the absence of distant metastases and sarcomatoid transformation.

Spinal adrenal cortical adenoma with oncocytic features: report of the first intramedullary case and review of the literature.

Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent surgical intervention. A well-circumscribed, approximately 3 x 2 cm, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS.

Oncocytic metaplasia of canine palatine ductal epithelium.

Oncocytic metaplasia of palatine gland ducts was demonstrated by light and electron microscopy in seven out of 54 dogs. Oncocytes were recognized as distinct swollen epithelial cells with bright eosinophilic cytoplasm, small dark nuclei and scattered microvilli at the luminal surface. Their cytoplasm contained numerous tightly packed mitochondria, which varied in size and shape. Some oncocytes formed nodular hyperplastic foci that were easily recognized by low-power light microscopy. Oncocytic metaplasia appears to be a common incidental finding in palatine ductal epithelium of older dogs.

Oncocitoma nasofaríngeo como causa de disfunción tubárica / Nasopharyngeal oncocytoma as a cause of Eustachian tube dysfunction

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Oncocytes, oxyphils, Hürthle, and Askanazy cells: morphological and molecular features of oncocytic thyroid nodules.

Our understanding of oncocytic change in thyroid nodules is evaluated in light of the recent progress in understanding the mitochondrial DNA, its mutations, and somatic mutations that affect mitochondrial function. These changes are largely unrelated to the genetic events that result in proliferation and neoplastic transformation of thyroid follicular epithelial cells. The criteria for diagnosing lesions that are composed predominantly of oncocytic cells are the same as those applied to follicular lesions that do not contain oncocytic cells, including follicular variant papillary carcinomas, based on nuclear morphology, immunohistochemical profiles, and molecular markers.

Primary oncocytic carcinoma of the salivary glands: a clinicopathologic and immunohistochemical study of 12 cases.

Oncocytic carcinoma (OC) of salivary gland origin is an extremely rare proliferation of malignant oncocytes with adenocarcinomatous architectural phenotypes, including infiltrative qualities. To help clarify the clinicopathologic and prognostic features of this tumor group, herein, we report 12 OC cases arising from the salivary glands, together with follow-up data and immunohistochemical observations. There were 10 males and 2 females with an age range of 41 to 86 years (median age: 61.3 years). Most occurred in the parotid gland (10/12) with one in the palate and one in the retromolar gland. The tumors were unencapsulated and often invaded into the nearby gland, lymphatic tissues and nerves. The neoplastic cells had eosinophilic granular cytoplasm and round vesicular nuclei with prominent red nucleoli. Ultrastructural study, PTAH, and immunohistochemistry staining confirmed the presence of numerous mitochondria in the cytoplasm of oncocytes. Cellular atypia and pleomorphism varied in the current series. Double nuclei and mitoses were observed in some cases, while one case that showed mild cellular pleomorphism but had local invasion following local recurrence was also identified as an OC. Of the 11 cases with follow-up information, 7 cases had local recurrence. Regional or distant metastases were found in 6 and 4 cases, respectively. Five-year disease-specific survivals were 54.9%. In summary, OC of salivary gland origin is a high-grade tumor, often with local recurrence, regional or distant metastasis, diagnosis of which based on a combination of clinical and histopathological features. Immunohistochemistry for mitochondria is considered as a practical and helpful adjuvant diagnosis. Complete surgical excision is the treatment of choice while the role of radiotherapy or chemotherapy is controversial, and careful follow-up is necessary.

Preparation and quality test of superparamagnetic iron oxide labeled antisense oligodeoxynucleotide probe: a preliminary study.

Molecular imaging of tumor antisense gene techniques have been applied to the study of magnetic resonance (MR) gene imaging associated with malignant tumors. In this study, we designed, synthesized, and tested a novel molecular probe, in which the antisense oligodeoxynucleotide (ASODN) was labeled with superparamagnetic iron oxide (SPIO), and its efficiency was examined by in vitro MR imaging after SK-Br-3 mammary carcinoma cell lines (oncocytes) transfection. The SPIO-labeled ASODN probe was prepared through SPIO conjugated to ASODN using a chemical cross linking method. Its morphology and size were detected by atomic force microscope, size distribution were detected by laser granulometer, the conjugating rate and biological activity were determined by high performance liquid chromatography, and the stability was determined by polyacrylamide gel electrophoresis. After that, the probes were transfected into the SK-Br-3 oncocytes, cellular iron uptake was analyzed qualitatively at light and electron microscopy and was quantified at atomic absorption spectrometry, and the signal change of the transfected cells was observed and measured using MR imaging. The morphology of the SPIO-labeled ASODN probe was mostly spherical with well-distributed scattering, and the diameters were between 25 and 40 nm (95%) by atomic force microscope and laser granulometer, the conjugating rate of the probe was 99%. Moreover, this probe kept its activity under physiological conditions and could conjugate with antisense oligodeoxynucleotide. In addition, light microscopy revealed an intracellular uptake of iron oxides in the cytosol and electron microscopic studies revealed a lysosomal deposition of iron oxides in the transfected SK-Br-3 oncocytes by antisense probes, some of them gathered stacks, and the iron content of the group of transfected SK-Br-3 oncocytes by antisense probe is significantly higher (18.37 +/- 0.42 pg) than other contrast groups, the MR imaging showed that transfected SK-Br-3 oncocytes by antisense probe had the lowest signal of all. The SPIO-labeled ASODN probe shows unique features including well-distributed spherical morphology, high conjugating rate and loading efficiency, and the signal intensity of SPIO-labeled ASODN-transfected SK-Br-3 oncocytes is reduced in MR imaging. These results indicate that the SPIO-labeled ASODN probe is potentially useful as a MR targeting contrast enhancing agent to specifically diagnose tumors which had over-expression of the c-erbB2 oncogene at an early stage.

Sarcomatoid acquired cystic disease-associated renal cell carcinoma.

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.

Bilateral oncocytic malignant melanoma in axillary lymph nodes without evidence of an extranodal primary.

A malignant melanoma was diagnosed in an axillary lymph node of a 49-year-old man. The tumor was examined by electron microscopy and was found to be composed of large oncocytic cells, filled with abundant mitochondria. No primary tumor could be identified on the skin or within internal organs. Approximately 2 years after the initial diagnosis, the patient presented with malignant melanoma in an axillary lymph node on the contralateral side. The second tumor also expressed the same oncocytic phenotype, favoring the common origin of both tumors. These data illustrate that oncocytic melanomas may retain their oncocytic phenotype during metastatic dissemination.