Oncocytic liver cell adenoma

A 46-year-old woman underwent right hepatic lobectomy for the removal of a solitary liver tumour from a non-cirrhotic liver. The macroscopic and light microscopic features were those of a liver cell adenoma but the cells appeared oncocytic. Electron microscopy confirmed the numerous mitochondria characteristic of oncocytes. The difficulty of distinguishing oncocytic liver cell adenoma from fibrolamellar hepatocellular carcinoma is discussed.     

Oncocytic meningioma. Case report

Among the histological variants of meningiomas the oncocytic subtype is rarely observed. Up-today, only six cases of oncocytic meningioma are described. This subtype of meningiomas shows an aggressive behavior and recurrences are more frequent. We describe a case of oncocytic meningioma in a 78-years-old woman. The patient had a history of breast cancer diagnosed 9 years before the brain biopsy; bilateral mastectomy and adjuvant chemotherapy was performed. She had a right frontal tumour measuring 3 cm in diameter. The patient is alive and well eleven months after surgery. The tumour was composed by large polygonal neoplastic cells with finely granular eosinophilic cytoplasm. Neoplastic cells were arranged in sheets and nests delimited by thin fibrous septa rich in vessels. Psammomatous bodies were also present. Mitoses were rare and necrosis was absent. Oncocytic differentiation was demonstrated by conventional histology and immunohistochemistry. Immunohistochemistry revealed a strong and diffuse positivity for antimitochondrial antiserum, vimentin and EMA; a focal reactivity for cytokeratin was observed. The rarity of oncocytic meningiomas is underlined with only six cases described in the world literature. The immunophenotypic profile and the differential diagnosis of the neoplasm is discussed and the concept of oncocytic meningioma as a distinct entity of tumour is emphasized.     

Cytokeratin 14 immunoreactivity distinguishes oncocytic tumour from its renal mimics: an immunohistochemical study of 63 cases

AIMS: The cytokeratin 14 (CK14) expression in oncocytomas or oncocytic tumours of various tissue origins has not been established. We have studied CK14 expression in 30 cases of oncocytic tumours of various tissue origins and 33 cases of renal cell carcinoma with overlapping features (mimics) by immunohistochemistry. METHODS AND RESULTS: Immunohistochemistry (ABC-HRP method) was performed for detection of CK14 in 30 cases of oncocytic tumour and 33 cases of renal mimics. To demonstrate CK14 specificity and sensitivity in oncocytic tumours, mES-13 (an anti-mitochondrial monoclonal antibody) immunohistochemistry was also performed in 20 of 30 cases on oncocytic tumour and all 33 cases of renal mimics. We found that all 30 cases of oncocytic tumour showed cytoplasmic CK14 positivity. All 20 cases of oncocytic tumour studied with mES-13 were positive. CK14 immunoreactivity was identified in only four cases of renal cell carcinoma (one conventional renal cell carcinoma with granular cytoplasm and three chromophobe renal cell carcinomas with eosinophilic cytoplasm). In contrast, all 33 cases of renal cell carcinoma were positive for mES-13 to varying degrees. CONCLUSION: The homogeneous, cytoplasmic, and granular CK14 immunoreactivity is sensitive and specific for oncocytic tumours, whereas CK14 immunoreactivity in renal mimics is light and sporadic with peripheral accentuation.     

Oncocytic metaplasia of the nasopharynx or extra-parotid Warthin's tumour?

A case of oncocytic metaplasia obstructing the Eustachian tube in an elderly patient is described. Histologically, it was similar to Warthin's tumour of the parotid gland. The lymphocytes were predominantly T cell, unlike those of Warthin's tumour which are predominantly B cell. It is proposed that oncocytic metaplasia represents an early stage in the evolution of Warthin's tumour.     

Pancreatic serous microcystic adenoma with extensive oncocytic change

Herein is reported a case of pancreatic serous microcystic adenoma with extensive oncocytic change in a 73-year-old woman. Histologically the tumor consisted of numerous small cysts, separated by thin or broad fibrous septa. These cysts were lined with uniform cells having abundant eosinophilic granular cytoplasm, which was negatively or weakly stained with PAS. Immunohistochemically, the cyst-lining cells were positive for cytokeratin (CK) 7, CK19, MUC1, MUC6, α-inhibin, and neuron-specific enolase (NSE), and negative for CK8, CK20, MUC2, and MUC5AC; these immunoprofiles coincide with those of serous microcystic adenoma. Immunostaining with anti-mitochondrial antibody showed dense granular positivity in the cytoplasm, which suggested an oncocytic phenotype. Thus, this case is considered a variant of serous microcystic adenoma characterized by extensive oncocytic change. To the authors' knowledge no similar case has been reported in the literature. It may pose problems in the differential diagnosis of the cystic pancreatic tumors with oncocytic change, but can be diagnosed on histology and immunohistochemistry.     

In situ oncocytic change in association with multiple renal cell adenocarcinomas

We report a case of in situ oncocytic change in association with two low-grade renal cell adenocarcinomas and one contralateral low-grade oncocytic adenocarcinoma. The in situ oncocytic change showed abundant cytoplasmic mitochondria confirmed by ultrastructural examination and phosphotungstic acid-hemotoxylin staining. In addition, this in situ oncocytic change expressed cytokeratin CAM 5.2 in the absence of cytokeratin AE1/AE3, as reported in oncocytic renal cell adenocarcinomas. Further study of in situ oncocytic change identified in kidneys resected for adenocarcinomas with regard to follow-up and management of the contralateral kidney seems indicated.     

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.     

Papillary cystic type of acinic cell carcinoma of parotid: fine needle aspiration cytological features of a high grade variant with oncocytic metaplasia

A 60-year-old female developed a right parotid swelling six months after surgery for intra-oral squamous cell carcinoma. Fine needle aspiration (FNA) cytological smears showed dissociated large and small pleomorphic tumour cells with abundant mitoses and oncocytic features. A cytological diagnosis of parotid acinic cell carcinoma (ACC) was made. Histological study of the subtotal parotidectomy specimen showed a papillary cystic variety of acinic cell carcinoma (ACC-PCV). FNA cytological features in this case of ACC-PCV differs from the two previously reported cases in that it showed prominent oncocytic and high grade features and absence of papillary pattern in the cytological smears. ACC-PCV is an uncommon tumour and knowledge of its varied FNA cytological features is important for the diagnosis of this neoplasm.     

Some histological remarks on the fibrolamellar carcinoma of the liver

Investigations on five fibrolamellar carcinomas of the liver suggest that this tumor originates from purely epithelial proliferations, while the ensuing fibrous growth leading to lamellar formations is but a secondary event. Nevertheless, progressing fibrosis has a considerable influence on cell shape as the surrounded cell complexes are quasi immured, and their supply and transport procedures impaired. Its influence further evokes a compensatory increase of mitochondria so that, in advanced cases, these cells may be mistaken for genuine oncocytes, although the appraisal of an oncocytic tumor is not confirmed. At this point only, increased amount of fibrinogen-containing (endoplasmic) vacuoles and PAS positive globuli are interpreted as phenomena of cellular retention, and so is the accumulation of unexcretable copper. Ultimately, this fibrous incarceration will cause cell death, destruction and depletion resulting in abundant scarring especially in the center of the focus, without, however, signalling any close relationship with focal nodular hyperplasia. Excess fiber formation exerts a proliferation-inhibiting effect resulting in slower growth and consequently, in the more favorable prognosis of this tumor of distinctive and well-characterized morphology.     

Adrenocortical oncocytoma.

The histopathology and ultrastructural features of an adrenocortical oncocytoma are reported. The tumour was discovered incidentally during investigation for hypertension in a 72 year old female. Oncocytic tumours of the adrenal cortex are rare, with only 20 examples described in English language reports. Most have been non-functioning and benign, like the present example. Molecular studies may help assess the significance of oncocytic change in the pathogenesis and behaviour of oncocytic neoplasms.     

Oncocytic glomus tumour: a new variant

A new variant of glomus tumour characterized by oncocytic change is reported. The light and electron microscopy and immunohistological findings are described. This is the first reported case of an oncocytoma of non-epithelial origin.     

Malignant epithelioid haemangioendothelioma of the liver: a clinicopathological and histochemical study of 12 cases

We describe the clinicopathological findings in 12 cases of hepatic epithelioid haemangioendothelioma in order to identify diagnostic and prognostic features of this unusual vascular neoplasm. Three main tumour patterns were observed histologically: (1) a peripheral pattern with neoplastic cells scattered between fairly normal liver cell plates; (2) a cellular pattern showing a confusing admixture of pleomorphic tumour cells and atrophied hepatocytes set in a small amount of fibrous stroma; and (3) a scarred pattern with sparse tumour cells in a dense fibrous matrix. There were two types of vascular invasion: tuft-like intravascular proliferations of epithelioid cells and fibro-thrombotic venous occlusions. Awareness of these different aspects is important, as they are variably sampled by biopsy needles. The clinical course in this series was less favourable than that previously reported. Eight patients have died, in six instances of liver failure within 4-41 months of diagnosis. Extensive involvement of both lobes of the liver heralds imminent hepatic failure. The slow growth of metastases may justify liver transplantation in order to prolong life.     

Adrenocortical oncocytoma: Case report with immunocytochemical and ultrastructural study

Summary An adrenocortical oncocytic neoplasm was detected incidentally in a 58-year-old man. The tumour weighted 315 g, showing haemorrhagic areas and broad fibrous bands. It was composed exclusively of large eosinophilic cells packed with mitochondria showing flat and infrequent tubulovesicular cristae and regression of steroid-related organelles. Occasional annulate lamellae and mitochondrial osmiophilic inclusions were present. Vimentin was diffusely expressed, whereas AE1/AE3 cytokeratin was detected in half of the cells; a focal punctate pattern of staining was exclusively observed for cytokeratin peptides 8 and 18. The patient had no evidence of disease 21 months after surgery.     

The C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours

Carriers of the C allele of the common C825T polymorphism in the GNB3 gene of the G protein have been associated with the development of follicular thyroid adenomas. Since the C allele of this polymorphism is related to a lower signalling capacity, it was speculated whether the C825T polymorphism may play a particular role in oncocytic thyroid tumours, which are recognized for their reduced ability to synthesize thyroid-specific proteins and hormones, although they possess an intact thyroid-stimulating hormone receptor-adenylyl cyclase system. Using pyrosequencing, both the genotype distribution and the allele frequency of the C825T polymorphism were investigated in a series of 104 patients with oncocytic thyroid tumours of follicular cell origin [58 adenomas, 41 follicular thyroid carcinomas (FTCs), and five papillary thyroid carcinomas (PTCs)]; the results were compared with those obtained from 321 age and gender-matched healthy blood donors and a series of 327 non-oncocytic thyroid tumours of follicular cell origin (119 adenomas, 80 FTCs, and 186 PTCs). Analysis of the genotype distribution (comparing oncocytic with non-oncocytic tumours of the present series) revealed a significantly increased odds ratio (OR) for CC versus TT (OR = 4.22; p = 0.011) and CC versus CT (OR = 1.62; p = 0.049) carriers to develop an oncocytic thyroid tumour; ORs to develop an oncocytic thyroid tumour were also increased comparing the genotype distribution between the group of oncocytic tumours and healthy controls for CC versus TT (OR = 3.73; p = 0.017) and CC versus all T carriers (OR = 1.56; p = 0.034). Oncocytic thyroid tumours as a group showed a statistically significant increase of the C-allele frequency when compared with all non-oncocytic tumours (p = 0.0039) as well as healthy blood donors (p = 0.017). The results strongly suggest that the C allele of the GNB3 C825T polymorphism of the G protein beta3-subunit is associated with an increased risk for the development of oncocytic thyroid tumours. This polymorphism may thus be considered a (co)factor favouring the development of oncocytic thyroid tumours, although the biological mechanism(s) underlying this association remain obscure.     

Oncocytic myoepithelioma and pleomorphic adenoma of the salivary glands

 Twenty oncocytic myoepitheliomas (MEs) and pleomorphic adenomas (PAs) were composed of interlacing fascicles of swollen spindle-shaped or/and epithelioid oncocytic myoepithelial cells showing intense finely granular immunoreactivity with anti-mitochondrial antibody. Focal vacuolation of the cytoplasm of oncocytic myoepithelial cells and their gradual transition into sebaceous metaplasia were observed in 3 cases. Another unusual feature found in 5 cases was the presence of slit-like adenomatoid spaces lined with double-layered oncocytic myoepithelium closely resembling Warthin’s tumour. The nuclei of oncocytic cells were characterized by enlargement, hyperchromasia and polymorphism, which should not be confused with malignancy. Oncocytic change in myoepithelial cells in MEs and PAs can cause pitfalls in the differential diagnosis of salivary gland tumours. We describe some unusual histological features associated with onococytic metaplasia in benign myoepithelial cell-derived salivary gland tumours, hoping to help to avoid the overdiagnosis of malignancy. Received: 24 September 1998 / Accepted: 31 January 1999     

Fibrolamellar carcinoma of the liver: the malignant counterpart of focal nodular hyperplasia with oncocytic change

A case of fibrolamellar carcinoma (FLC) in a noncirrhotic liver of a 20-year-old man is described. Gross features and the presence, among the tumor cells, of bile ducts, of thick-walled blood vessels and nerves, and, ultrastructurally, of myofibroblast-like cells are the most significant findings, suggesting that FLC is the malignant counterpart of focal nodular hyperplasia with oncocytic change. Histochemical and immunohistochemical methods demonstrate the presence inside the oncocytic tumor cells of copper, copper-binding protein, and alpha 1 antitrypsin. The pathogenesis and the significance of these findings then are discussed and related to the restricted capacity of oncocytic cells to fulfill normal cellular function.     

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.     

Poorly differentiated oncocytic thyroid carcinoma--diagnostic implications and outcome

Dettmer M, Schmitt A, Steinert H, Moch H, Komminoth P & Perren A
(2012) Histopathology  60, 1045–1051 Poorly differentiated oncocytic thyroid carcinoma – diagnostic implications and outcome Aims: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. Methods and results: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan–Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour‐specific survival but no difference for relapse‐free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. Conclusions: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities.     

Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms

Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.     

Systemic mastocytosis following a malignant ovarian germ cell tumour

Cases of mediastinal germ cell tumours associated with haematological disorders (two cases of systemic mastocytosis included) have been reported previously. This combination is more frequent than would be expected by chance alone. We report the case of a 30-year-old woman, who presented with a systemic mastocytosis following a malignant ovarian germ cell tumour which was treated by chemo- and radiotherapy. The patient predominantly complained of skeletal pains, which led to an erroneous radiological diagnosis of fibrous dysplasia for years. An aggressive variant of systemic mastocytosis was diagnosed on bone marrow examination. Systemic mastocytosis was confirmed by splenectomy, liver biopsy and finally autopsy. The present case is unique because of the ovarian location of the germ cell tumour. We suggest our observation could be related to the broad group of haematological malignancies associated with germ cell tumours.