Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Background:  Oncocytic lesions, particularly frequent in the salivary glands, are characterized by cells with an atypical accumulation of mitochondria. This accumulation has been recognized as a compensatory mechanism to intrinsic functional defects of these organelles, resulting in energy production impairment and increased generation of reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂). Peroxiredoxin I (Prx I) is a H₂O₂ scavenging protein and the expression of its yeast homolog was reported to be influenced by mitochondrial function.
Methods:  In this study, we evaluated Prx I expression in oncocytic lesions of salivary glands by immunohistochemistry.
Results:  Our results showed that Prx I is overexpressed in oncocytes regardless of the salivary gland lesion where they appear.
Conclusions:  These results suggest that Prx I expression in oncocytes is related to its ability to decompose mitochondrial-derived H₂O₂ and that it could provide to the cells a protective role in an environment that, by continuously producing potential DNA-damaging ROS, predisposes to genome instability and cellular transformation.     

Oncocytic versus mitochondrion‐rich follicular thyroid tumours: should we make a difference?

Aims: To separate true oncocytic neoplasms from mitochondrion‐rich non‐oncocytic lesions based on the intracellular relationship between major cell organelles, and to establish the diagnostic and clinical relevance of this distinction. Methods and results: Tissue samples from 276 follicular adenomas, 194 follicular carcinomas, 162 normal thyroids and 296 non‐neoplastic lesions were classified as conventional, mitochondrion‐rich or oncocytic based on the immunohistochemically assessed quantity and intracellular distribution of mitochondria and endoplasmic reticulum (ER) and nuclear position. Pathological and clinical features were compared among the groups. In oncocytes, densely packed mitochondria resulted in homogeneous immunolabelling of basal cytoplasmic regions, whereas ER and the nuclei were typically displaced to the apical position. This aberrant organelle distribution was not observed in non‐oncocytes, which allowed reliable distinction between oncocytic and mitochondrion‐rich lesions. Clinically, mitochondrial increase in non‐oncocytic lesions was associated with neoplasia, malignancy and higher cancer recurrence rates. Similar correlation, albeit less pronounced, was observed within the oncocytic tumour group. By contrast, oncocytic change per se was not associated with neoplasia, malignancy or cancer aggressiveness. Conclusions: True oncocytic neoplasms can be distinguished from mitochondrion‐rich non‐oncocytic tumours based on aberrant distribution of all major cell organelles. This distinction has immediate clinical relevance and should be implemented in practice.     

Identification of oncocytic lesions of salivary glands by anti-mitochondrial immunohistochemistry

 

Aims:

To evaluate the immunohistochemistry using an anti-mitochondria antibody in the investigation of various oncocytic lesions of the salivary glands.  

Methods and results:

Ten cases of adenolymphoma (Warthin's tumour) and one case each of benign oncocytoma and oncocytic carcinoma of the salivary glands were examined. Normal salivary glands were also tested. They were investigated immunohistochemically using mouse monoclonal antibody against human mitochondria. In normal salivary glands, epithelial cells of the striated ducts showed a thick linear immunoreactivity, which corresponded well to the intracytoplasmic distribution pattern of mitochondria. In addition, a small number of swollen epithelial cells showing an intense, finely granular immunoreactivity in the cytoplasm were scattered in the ductal system and acini ('oncocytic metaplasia'). Almost all neoplastic cells involved in adenolymphoma, benign oncocytoma, and oncocytic carcinoma showed an intense, finely granular immunoreactivity in the cytoplasm.  

Conclusions:

Immunohistochemistry using the anti-mitochondria antibody proved to be a highly sensitive and specific method for light microscopic identification of mitochondria and superior to routine H & E or PTAH stain especially in the detection of isolated oncocytic cells.     

嗜酸细胞乳头状肾细胞癌3例报道并文献复习

目的:探讨嗜酸细胞乳头状肾细胞癌(OPRCC)的临床病理学特点。方法:对3例OPRCC进行光镜观察、免疫组织化学标记及荧光原位杂交检测并复习相关文献。结果:3例OPRCC中,2例男性,1例女性,年龄分别为41、45、65岁。3例均为体检发现肾肿块,例1及例2肿块位于肾下极,例3位于肾中上级,与周围肾组织分界清楚,长径分别为3.0、3.5及4.5 cm,瘤细胞细胞质丰富,嗜酸性,核Fuhrman分级2~3级,瘤细胞排列呈乳头状,乳头内见泡沫细胞聚集。免疫表型3例瘤细胞vimentin、CK7、CD10、AMACR、EMA、CK均阳性,而TFE3、CD15、CD117、RCC、E-cadherin等均阴性。荧光原位杂交检测显示3例瘤细胞均有7、17号染色体扩增。结论:OPRCC是肾细胞癌的罕见亚型,免疫表型及分子遗传学与1型乳头状肾细胞癌相似。应与嗜酸细胞瘤、嫌色性肾细胞癌、Xp11.2易位肾细胞癌等相鉴别。     

ONCOCYTES OF THE THYROID: A NEUTRAL RED DYE UPTAKE STUDY

Oncocytosis and oncocytomas have attracted attention because on the one hand there have been reports of the favourable prognosis and generally benign nature of oncocytic tumours, while on the other hand, Hurthle cell change in thyroid neoplasms have been reported to be correlated with aggressive biological behaviour and a significantly worse clinical course. Presently, there appear to be two schools of thought on the significance of oncocytosis: (i) a process where there is redifferentiation of cells with involvement in the pathogenesis of cancer; and (ii) a compensatory process for ‘functional exhaustion’ of the cell. Many aspects of oncocytosis seem unclear. In this study, transmission electron microscopy is used to demonstrate the presence of thyroid oncocytes in the hemithyroidectomy specimen of a patient with focal lymphocytic thyroiditis. Tissue sections from this specimen did not display preferential uptake of neutral red dye, a distinctive characteristic of M-phase cancer cells which was previously reported. The findings seem to suggest that oncocytes are not cells with distinctive proliferative potentials. If that were the case, then oncogenesis or cancer cell progression and oncocytosis may not be convergent processes.     

原发性胆汁性肝硬化肝内小胆管的超微病理学研究

本文对4例原发性胆汁性肝硬化肝穿组织肝内小胆管进行了光镜和电镜观察。结果显示,肝内间隔和小叶间胆管上皮主要呈现三种变化,一少部分上皮细胞呈再生特征;大部分细胞则呈退行性变化;间隔胆管内还有为数甚少,以胞浆内充满大量线粒体为特征的嗜酸性细胞出现。上述变化提示,在致病因子作用下,肝内小胆管上皮同时存在损伤与修复再生过程,本研究首次在肝内间隔胆管内发现的嗜酸性细胞,对进一步阐明本病的发病机制具有一定意义。     

Ultrastructural Analysis of Apocrine Carcinoma of the Human Breast

A case report with ultrastructural analysis of an apocrine carcinoma of the breast is presented. The key finding with electron microscopy is numerous large mitochondria with abundant incomplete cristae. The ultrastructure of this tumor is compared to the ultrastructure of apocrine cells in the skin, oncocytes, and apocrine metaplastic cells of the breast. The apocrine carcinoma cells have some of the features of typical metaplastic breast epithelium and some features of oncocytes. Their exact origin remains open to speculation.     

Oncocytic papillary neoplasms of the biliary tract: a clinicopathological, mucin core and Wnt pathway protein analysis of four cases

AIMS: Oncocytic change in papillary neoplasms of the biliary tract is a very uncommon finding with little known about pathogenesis, immunophenotype and prognosis, especially in comparison to similar lesions in the pancreatic ductal system. We report four cases of oncocytic biliary intraductal papillary neoplasms (IPNs), highlighting the clinicopathological characteristics of these tumours, the immunohistochemical profile with regard to Wnt pathway proteins and mucin core protein (MUC) status, and compare these findings with the oncocytic variant of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS: Four cases of oncocytic IPN of the extrapancreatic, biliary tree (two with accompanying invasive carcinomas) were examined for mucin profiles and Wnt signalling proteins. The cases were stained for: beta-catenin, c-myc, glutathione synthase kinase (GSK), E-cadherin, cyclin D1, and adenomatous polyposis coli (APC), and MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B and MUC6, using standard immunohistochemistry. RESULTS: The cases occurred in three males and one female, ranging in age from 59 to 81 years. The lesions caused obstructive symptoms related to the biliary tree as well as non-specific abdominal symptoms. Typically, cystic lesions were noted grossly. All four of the IPNs were composed of distinctive oncocytic cells. The invasive carcinomas accompanying two of the cases were also composed of oncocytes. None of the cases showed aberrant expression of the Wnt signalling proteins, although cyclin D1 was markedly over-expressed in all four cases. Three of four cases showed the following mucin profile: MUC3, MUC4, MUC5AC, MUC5B and MUC6 positive. CONCLUSIONS: The Wnt pathway proteins (especially beta-catenin and E-cadherin) are expressed normally in oncocytic variants of intraductal papillary neoplasms of the biliary tree, and the mucin profile is similar to their counterparts in the pancreas.     

Fine‐needle aspiration biopsy of recurrent oncocytic carcinoma of parotid gland

A 65‐year‐old man presented with a right cheek mass. His past history was significant for resection of primary oncoctyic carcinoma of the right parotid gland 5 years ago. Fine‐needle aspiration biopsy of the right cheek mass was performed and demonstrated oncocytic cells without significant cytologic atypia. On the basis of the past history and comparison of the histology of previously resected specimen, the cytologic impression was consistent with recurrent oncocytic carcinoma of the salivary gland. The cytologic differential diagnosis should include other primary salivary gland neoplasms and metastatic disease. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Oncocytic lipoadenoma of the parotid gland: a report of a new case and review of the literature

Oncocytic lipoadenoma is a rare salivary gland tumour composed of adipose tissue and oncocytic epithelial cells in varied proportions. This tumour is still not included in the current WHO classification of salivary gland neoplasms. We herein report a further case of oncocytic lipoadenoma originating in the parotid gland of a 55-year-old woman. The tumour presented as a slowly growing asymptomatic left-sided parotid gland mass. The resected tumour measured 2.7 cm in maximum diameter and was composed of oncocytoma-like epithelial component admixed with mature adipocytes that made up 10% of the whole mass. Foci of sebaceous differentiation were seen. This rare variant of lipomatous salivary gland tumours is in need of more recognition and should be distinguished from other fat-containing salivary gland lesions, particularly lipomatous pleomorphic adenoma and myoepithelioma.