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Bronchopulmonary carcinoids are low-grade tumors for which the standard treatment is surgical resection. We retrospectively evaluated the surgical outcomes. Thirteen patients underwent surgical resection for them at our institution between January 2005 and December 2016. We collected their clinicopathologic data to evaluate surgical outcomes. The 13 patients comprised seven men and six women. Complete resection was performed in all cases. All the tumors were typical carcinoids, including one oncocytic carcinoid which showed highest fluorodeoxyglucose (FDG) uptake (SUVmax 45.7). The 5-year overall survival rates were 100%. The only patient with oncocytic carcinoid developed recurrence of liver metastasis 49 months after the primary lung resection. The metastasis showed low FDG uptake (SUVmax 2.8) and its histology was typical carcinoid and not oncocytic carcinoid. Surgical outcomes in our patients were favorable. In oncocytic carcinoid, metastatic site may have a radiologic and histologic appearance different from the primary tumor.

Abundant calcifications and clear-cell change may occur in oncocytic thyroid adenoma (OTA). We aimed to report the features of a case of OTA peculiar by the presence of extensive calcifications and of a clear-cell component. The OTA was detected on a right thyroid lobectomy specimen. Clear-cell change was observed in 15%-20% of the cells. Numerous, focally confluent psammomatoid calcifications, resulting in macrocalcifications, were identified. The nodule cells, uni- or multinucleated oncocytes, including those with clear cytoplasm, expressed heterogeneously TTF1, S100 protein, Bcl2, CD10, as well as CD138 and CD56. Lipid-droplet markers adipophilin and TIP47 were also expressed. In conclusion, we report a rare type of OTA, peculiar by the presence of numerous psammomatoid calcifications and of macrocalcification and by the presence of clear-cell change. Heterogeneity in membrane CD56 and/or CD138 expression as well as cytoplasmic heterogeneity of Bcl2 and lipid-droplet marker TIP47 might be relevant for calcification and clear-cell change, requiring further investigation.

Objective The Italian reporting system for thyroid cytology classifies indeterminate lesions as TIR3A (low risk) or TIR3B (high risk) and is meant to provide practical guidance rather than a detailed consideration of morphological features. We aimed to assess which cytological features have the most diagnostic value and whether they are effective in classifying nodules as either TIR3A or TIR3B and in predicting histological outcomes. Methods Thyroid fine-needle aspirates from 111 indeterminate nodules were reviewed blinded to clinical information, TIR3A/TIR3B classification, and histology in order to assess which cytological features (pooled into artefacts, smear background, architectural and nuclear atypia, and oncocytes) differentiate TIR3A from TIR3B, and benign from malignant histological outcomes. Results Of the cytological features examined, those specific for TIR3B included high cellularity, nuclear atypia, oncocyte predominance and transgressing vessels. Features specific for TIR3A included artefacts, low cellularity and oncocyte sparseness. Other features, such as microfollicules/trabeculae, were non-specific. Due to the different distributions of these features, three TIR3B subgroups were identifiable: follicular lesions with oncocytic changes, pure follicular lesions, and follicular lesions with nuclear atypia, whereas no subgroups were identifiable in TIR3A. Nuclear atypia was a significant indicator of malignancy, whereas oncocyte predominance was not a reliable predictor of malignancy. High cellularity and microfollicules/trabeculae were not indicative of any histological outcome. Conclusions The majority of the assessed features were good predictors of histological outcomes. The TIR3A category included undefined nodules due to the absence of characterising features, whereas the TIR3B category included nodules with a greater number of distinguishing features.

Granular cell tumors (GCTs) are uncommon neoplasms with recently postulated origin from Schwann cell or neural crest. It can appear in different parts of the body and is most commonly found in the tongue. The cutaneous presentation is not that uncommon. Fine needle aspiration cytology (FNAC) has been suggested to be the diagnostic modality of choice. It will help to differentiate benign tumors from malignant ones and to differentiate GCT from frequent misdiagnoses such as granular histiocytic reaction, xanthogranuloma, rhabdomyoma, oncocyte rich lesions, alveolar soft part sarcoma (ASPS), epithelioid sarcoma, and carcinoma. We report two cases of GCT who presented with subcutaneous swellings in the right thigh and the left lumbar region for 24 months and 18 months, respectively. In the first case, a cytodiagnosis of chronic inflammation showing histiocytes was suggested while GCT was found in the second case. Subsequent histologic examination of the first case and immunocytochemistry in the second case gave the confirmatory diagnosis of GCT.

Sialolipoma, a rare tumor of the salivary gland, is a recently described variant of salivary gland lipoma. Oncocytic sialolipoma was first described by Pusiol et al. in 2009. We report the case of an oncocytic sialolipoma of the submandibular gland in a 43-year-old female. Excision of the tumor was performed with preservation of the submandibular gland. The tumor had a thin, fibrous capsule and consisted of abundant adipose tissue, an oncocytic nodule, and scattered normal glandular structures surrounded by adipose tissue. Four cases of sialolipoma of the submandibular gland, including the present case, were reviewed. All 4 tumors were developed on the right submandibular glands, with a composition of adipose tissue as high as that of sialolipoma of the parotid gland; in contrast to previous reports, three cases were in females. As newly described tumor type, care should be taken to distinguish oncocytic sialolipoma from other salivary gland neoplasms such as simple lipoma, pleomorphic adenoma, or oncocytoma.

Extramedullary hematopoiesis (EMH) is a phenomenon in which hematopoietic cells are found in sites other than the bone marrow. It is usually observed in the liver and spleen but may occasionally be found within solid tumors. The current case report presents a 69-year-old female patient who presented with a renal cyst. Histopathological examination following surgical removal of the cyst revealed a lining of oncocytic- and chromophobe-type cells with capsular invasion and a mass forming EMH with evident bone trabeculae within the cyst wall. Circulating hematopoietic stem cells in the blood and their colonization within tissues is discussed in the present case report, emphasizing certain types of renal cell carcinoma.

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.

This is a benign neoplasm composed predominantly of monotonous sheets of plump oncocytes. By electron microscopy, the cytoplasm of the oncocyte is packed full with mitochondria. Focal areas of the tumor contain spindle cells with abundant intracytoplasmic granular deposits of brown melanin pigment that contains melanosomes.

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.

Objectives: The purpose of this study was to define the clinicopathologic features and outcome of the oncocytic variant of papillary thyroid carcinoma (OVPTC) with a review of the literature. Methods: Twenty-three patients with OVPTC over a 10-year period were studied. Demographic, clinical, and histopathologic features and outcome data were analyzed retrospectively. Results: Seventeen women and 6 men, ages ranging from 20 to 76 years (95% confidence interval, 43.0 to 54.48), were studied. Cervical lymph node involvement was found in 43.4% of the patients. Most of the recurrences were associated with thyroid masses greater than 2 cm in diameter. Evaluation of the overall survival data by the Kaplan-Meier method revealed that most recurrences took place earlier than 30 months, and the majority of patients (74%) were well, with no evidence of disease, up to 78 months after the last treatment. All of the OVPTC cases presented as nonencapsulated tumors, and 78.2% demonstrated extrathyroid stromal invasion. Conclusions: OVPTC is a unique variant of papillary thyroid carcinoma that has distinctive clinicopathologic features. Since OVPTC is often associated with local invasion and may involve cervical lymph nodes, it may require more extensive surgery than classic papillary thyroid carcinoma.

Intrahepatic cholangiocarcinoma (ICCA) comprises 10% of all cholangiocarcinoma (CCA). It can be divided into three macroscopic subtypes, the least common of which is characterized by intraductal growth and believed to be more amenable to good outcomes with surgical resection compared to other ICCA. Recently, the rare finding of oncocytic differentiation has been described in this subtype and termed «intraductal oncocytic papillary neoplasm» (IOPN), but it remains unclear if the presence of oncocytes confers a different tumor behavior. We present the eighth reported case of IOPN, which to our knowledge, is the first such case that, due to its location and vascular compromise, required orthotopic liver transplantation (OLT). This case adds to the little that is known about the behavior of IOPN and supports the observation that resection, or OLT when resection is not possible, is a valid treatment option.

The oncocyte is a cell characterized by capacious, eosinophilic, finely granular cytoplasm, and lesions composed primarily of oncocytes are termed oncocytomas. Whereas oncocytic metaplasia has been reported in various cutaneous neoplasms, oncocytomas typically occur in the kidneys, thyroid and salivary glands and are uncommon in the dermatopathology literature. We present three cases of cutaneous oncocytoma so that dermatopathologists are cognizant of this uncommon entity. Although some believe that oncocytomas are locally aggressive lesions, our cases indicate that their clinical course is perhaps as banal as their histology.

A very rare case of intraductal oncocytic papillary carcinoma of the liver is reported. A 63-year-old Japanese man was admitted to our clinic because of abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe. Combined percutaneous and endoscopic retrograde cholangiographies revealed the unilocular cystic neoplasm contained a lot of mucus and communicated with the left segmental intrahepatic bile duct, and that mucus filled the left segmental and hepatic ducts. Left lobectomy was performed. The postoperative course was good, and the patient is free of disease 30 months after operation. Pathological examination revealed that the cavity of the neoplasm was continuous with the left segmental intrahepatic bile duct, and that a lot of mucus was present in the neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm consisted of papillary growth of atypical epithelial cells with oncocytic changes. Atypical goblet cells were also recognized. No invasion into the surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion occasionally showed epithelial dysplasia and contained a lot of mucus. Immunohistochemically, the tumor cells were rich in mitochondria and were immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous mitochondria and mucus droplets. Intraductal neoplasm communicating with the intrahepatic bile ducts has rarely been reported. The present case suggests that intraductal oncocytic papillary neoplasm, as described in the pancreas, may also occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm may express hepatocellular and pancreatic acinar phenotypes.

OBJECTIVE: To assess the relevance of (99m)Tc-SestaMIBI (MIBI) scan in the diagnostic evaluation of thyroid nodules with oncocytic cytology. SUBJECTS AND METHODS: Twenty-four patients with a single (or prevalent) 'cold' solid nodule with Hurthle cells (HC) at fine needle aspiration cytology (FNAC) were studied. Cytological diagnosis of oncocytic metaplasia (OM) or HC tumor (HCT) was made when HC on the smear were comprised 10-75%, or >75%. Nodules concentrating MIBI at early and late (2 h after washout) stages were considered MIBI-positive. In all cases histological findings were obtained after total thyroidectomy. RESULTS: FNAC was malignant or suspect for malignancy in 16 cases (six HCT and 10 OM) and not suspect in eight (two HCT and six OM). Histological examination revealed 14 malignant tumors (11 HCT and three OM), and 10 benign thyroid lesions (three HCT and seven OM). Sensitivity of FNAC for malignancy was 92.8% and specificity was 70.0%; HCT were identified by FNAC in only 35.7% and OM in 70.0% of cases. No significant difference in MIBI positivity was found between malignant and benign thyroid nodules. The highest percentage of MIBI positivity was found in HCT (78.5%), but MIBI-positive nodules were also observed in thyroid lesions with HC metaplasia (40.0%). CONCLUSIONS: MIBI scintiscan has no value in differentiating malignant from benign HC thyroid neoplasias. Most HCT are MIBI-positive, but this scan is not sufficiently specific to differentiate true HC neoplasias from other thyroid lesions showing HC at FNAC, although an MIBI-negative scan strongly supports the absence of true HCT.

Objective To review aspirates from histologically documented oncocytomas and Warthin's tumor (WT) to highlight the cytomorphologic findings and determine the difficulties encountered in typing oncocytepredominant aspirates. Study design Over a 19-year period (1982-2000) we reviewed aspirates from 45 cases with an oncocyte preponderance. In 24 of them tissue for histologic examination was available (5 oncocytomas and 19 WT). Results In 4 of the 5 histologically documented oncocytomas the aspirates were cellular, with oncocytic epithelial cells in sheets, papillary fragments and singly. Epithelial atypia was minimal and lymphoid component absent, though scant proteinaceous material with a sprinkling of lymphocytes was seen. In WT moderate (35%) to abundant (28%) oncocytic epithelial cells were seen predominantly in a sheetlike arrangement with occasional papillary fragments and single cells. A variable quantity of lymphoid component was seen in 90% of the aspirates, with 88% of them showing a proteinaceous background accompanied by necrotic debris in 43% of cases. Squamous metaplasia was identified in 30% of cases, with 3 showing atypical squamous cells. In four cases the lymphoid component was scant and oncocytes abundant, and both possibilities were entertained. Conclusion Fine needle aspiration cytology is fairly accurate in the preoperative diagnosis of WT. When the lymphoid component, mucus and necrotic background are minimal or absent, the tumors can be confused with oncocytoma. In oncocytoma, the oncocytic epithelial cells are more often seen in papillary fragments, acini and singly in comparison to WT, where sheets of oncocytic cells are observed. Some degree of epithelial atypia can be seen in oncocyte-predominant benign lesions. Squamous metaplasia, especially if accompanied by atypia and necrosis, can prove challenging.

Oncocytosis is defined as a metaplastic change characterized by the presence of cells with finely granular eosinophilic cytoplasm caused by the accumulation of mitochondria. Although this histologic feature can be found in normal tissues, it can also be seen pathologically as a degenerative phenomenon, where an accumulation of mitochondria is thought to compensate for an uncoupling of oxidative metabolism secondary to cellular aging. Oncocytic metaplasia can be observed in a variety of cutaneous lesions but, to our knowledge, has not been described in melanocytic nevi. We retrospectively reviewed 87 melanocytic nevi from 83 patients that showed significant oncocytic change. We obtained patient clinical history through surveys completed by the patients' physicians. Ultrastructural studies were performed on 4 representative nevi to confirm the presence of increased mitochondria. We prospectively reviewed 100 randomly selected nevi looking for oncocytic changes. We subsequently did not find any correlation with patient demographics or medical histories. Histologic evaluation showed granular eosinophilic cytoplasm in 75% or greater of lesional cells in two thirds of cases. This phenomenon occurred in all types of melanocytic nevi. Ultrastructural studies revealed melanocytes with numerous mitochondria in close apposition to melanosomes. Focal oncocytic change was identified prospectively in 38 of 100 randomly selected melanocytic nevi. We conclude that oncocytosis in melanocytic nevi is a relatively common and underrecognized phenomenon.

Hürthle cell thyroid neoplasms are classified as variants of follicular neoplasms, but they have distinct clinicopathological features. Chromosomal aberrations by comparative genomic hybridization (CGH) are common in Hürthle cell neoplasms. However, there is currently only limited information concerning the relationship between the chromosomal aberrations by CGH and tumor behavior. We, therefore, investigated chromosomal aberrations in primary Hürthle cell neoplasms (13 carcinomas and 15 adenomas) using CGH and correlated the aberrations identified with tumor node metastasis (TNM) stage, tumor differentiation, capsular invasion, and tumor recurrence. Chromosomal aberrations were found in 62% (8 of 13) of carcinomas and 60% (9 of 15) of adenomas. Overall, common chromosomal gains were found on 5p (29%), 5q (36%), 7 (29%), 12p (14%), 12q (21%), 17p (29%), 17q (32%), 19p (32%), 19q (25%), 20p (21%), 20q (29%), and 22q (18%). Common chromosomal losses were found on 2q (18%) and 9q (18%). Thirty-eight percent (5 of 13) of carcinomas were TNM stage III, 31% (4 of 13) were moderately to poorly differentiated, and 46% (6 of 13) were intermediately to widely invasive. Recurrence occurred in 38% (5 of 13). Carcinomas that subsequently recurred had a greater number of chromosomal gains (9.0 vs. 1.3;0.005) and had more frequent chromosomal gains on 12q, 19q, and 20p (0.001), 5p, 7, 19p, and 20q (0.005), and 12p (0.01) than those that did not recur. Five of the eight (63%) patients with aberrations developed recurrence, whereas none of the five patients without aberrations developed recurrence. In conclusion, chromosomal gains by CGH on 5p, 7, 12p, 12q, 19p, 19q, 20p, and 20q in Hürthle cell carcinomas are associated with tumor recurrence. Such chromosomal aberrations may be predictive for recurrent disease in patients with Hürthle cell thyroid carcinoma.

We report 10 cases of an unusual type of gastric adenocarcinoma that occurred in elderly patients 58-81 years of age. Histologically, the tumors were well to moderately differentiated tubular adenocarcinomas with very eosinophilic, finely granular cytoplasm. Immunohistochemical stains for antimitochondrial antibody were strongly positive. Ultrastructurally, the tumor cells had numerous mitochondria in their cytoplasm and occasional intracytoplasmic lumina with associated long microvilli. These histologic and ultrastructural features are similar to those of parietal cells in normal gastric fundic mucosa, but immunohistochemical staining of the tumors using four different antiparietal cell antibodies (anti-H(+)-K(+)-adenosine triphosphatase antibodies) was negative in all cases. Therefore, we think that these tumors were not parietal cell carcinomas but could be termed oncocytic adenocarcinomas, or adenocarcinomas with oncocytic differentiation. Previously reported cases of parietal cell carcinoma have been said to have a favorable prognosis, but it will be necessary to study a larger number of cases to determine the prognosis of oncocytic adenocarcinoma.

Reduced HBME-1 immunoreactivity of papillary thyroid carcinoma and papillary thyroid carcinoma-related neoplastic lesions with Hurthle cell and/or apocrine-like changes Background: We have recently observed that Hurthle cell tumours and papillary thyroid carcinoma with tumour cells showing decapitation of luminal portion of the cytoplasm (apocrine-like changes) display negative or decreased immunoreactivity for HBME. The purpose of this study is to correlate papillary thyroid carcinoma with positive and negative immunoreactivity for HBME with the histopathological features. Methods and results: Two hundred and five thyroid neoplasms including carcinoma and adenomas were grouped into Hurthle cell tumours, tumours with or without some features of Hurthle cells, tumours with apocrine-like changes and adenomas with or without limited nuclear features of papillary thyroid carcinoma but not diagnostic for papillary thyroid carcinoma. All neoplasms were submitted for immunostaining with cytokeratin 19 (CK19) and HBME. Papillary thyroid carcinoma, follicular carcinoma and follicular adenoma that have areas of limited nuclear features but not diagnostic for papillary thyroid carcinoma showed stronger immunostaining for HBME than their respective counterparts with Hurthle cell changes. All Hurthle cell tumours showed negative to focal reactivity. This decrease of reactivity for HBME was proportional to the levels of Hurthle cell changes. In addition, focal to extensive apocrine-like changes were seen in most Hurthle cell neoplasms and rarely seen in non-Hurthle cell neoplasms. Apocrine-like changes abolished or decreased HBME immunoreactivity of papillary thyroid carcinoma and tumours with limited nuclear features. Immunostaining for cytokeratin AE3 was not affected by Hurthle cell or apocrine-like changes. Conclusions: All papillary thyroid carcinomas without Hurthle cell or apocrine-like differentiation are reactive for HBME. Hurthle cell tumours and tumours with Hurthle cell or apocrine-like changes show negative or focal reactivity for HBME. Except for this limitation, HBME is a sensitive marker for papillary thyroid carcinoma and tumours with limited nuclear features.

The authors report a case of oncocytic paraganglioma of the cauda equina in a 12-year-old girl who presented with lower back and leg pain on the right side of 6 months’ duration. Magnetic resonance imaging revealed an ellipsoidal, intradural, extramedullary mass causing cord compression at the level of L1. Total laminectomy was performed on T12 and L1, and the tumor was excised completely without difficulty despite adherence of the tumor to the spinal cord. Postoperatively, the leg pain and motor weakness were much improved. The use of electron microscopy, and the immunohistochemical demonstration of synaptophysin in this tumor, allowed a confident diagnosis of an oncocytic paraganglioma to be made. To the authors’ knowledge, this patient represents the first definite case of an oncocytic paraganglioma of the cauda equina in a child.

Although uncommon, Hurthle cell neoplasms have a characteristic histologic and cytologic features which often aid in the diagnosis of these lesions. In fine needle aspiration biopsies, determining malignant potential on cytologic features is challenging unless other evidence of malignancy (such as metastases) are known. The role of EUS-guided FNA in diagnosing superior mediastinal masses has been described previously. It's role in evaluating subcarinal metastases from lung cancer primaries have also heen studied. However we describe metastatic thyroid Hurthle cell carcinoma to the subcarina diagnosed through EUS-guided FNA combining the unique cytologic features o Hurthle cell neoplasms and the versatility ofthe endoscopic ultrasound to reach a diagnosis in this unusual neoplasm. Diagn. Cytopathol. 2013;41:977–979. © 2011 Wiley Periodicals, Inc.

Introduction.—Recent abstracts have emphasized the importance of recognizing intracytoplasmic lumen and transgressing vessels as useful criteria enabling distinction between Hürthle cells encountered in neoplastic and nonneoplastic thyroid aspirates. The purpose of this retrospective study was to evaluate if application of these criteria improves specificity and sensitivity of cytologic diagnosis of true Hürthle cell neoplasms. Materials and Methods.—We retrospectively reviewed 30 fine-needle aspirates of thyroid with cytologic diagnosis of Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid with prominent Hürthle cells (17 cases). All cases were evaluated for the presence of intracytoplasmic lumen and transgressing vessels and were reclassified as neoplastic or nonneoplastic based on the presence or absence of 1 or both of these criteria. Surgical follow-up was available in all cases. Results.—Surgical follow-up in 13 cases of Hürthle cell neoplasms revealed Hürthle cell carcinoma (3 cases), Hürthle cell adenoma (6 cases), and Hashimoto's thyroiditis (4 cases). Seventeen cases with nonneoplastic diagnosis revealed Hürthle cell carcinoma (1 case), Hashimoto's thyroiditis (12 cases), and nodular goiter (4 cases). After application of the previously mentioned cytologic criteria, the cytologic diagnoses were reclassified as Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid (17 cases). The true sensitivity of the test before and after the application of the criteria was 90% and 100%, respectively. The true specificity before and after the application of the cytologic criteria was 65% and 85%, respectively. Conclusions.—Intracytoplasmic lumen and transgressing vessels are helpful features in distinguishing neoplastic and nonneoplastic Hürthle cell thyroid lesions. Use of these criteria may improve the specificity and sensitivity of the cytologic diagnosis.

Adrenocortical tumor with oncocytic cells are exceptional. They are composed exclusively or almost exclusively of oncocytic cells, which are large cells with eosinophilic granulations, corresponding to numerous mitochondria in electronic microscopic examination. This tumor is usually non-functional and benign, and has to be differentiated from the adrenocortical carcinoma.

Background The cytopathologic features of oncocytic carcinoid tumor of the lung, a rare variant of carcinoid tumor that is composed exclusively of oncocytes, have not been described before in detail. Case The bronchial brush smears from an 80-year-old female with an endobronchial obstructive tumor showed single and loose clusters of tumor cells with abundant granular, eosinophilic cytoplasm. The differential diagnoses included oncocytic carcinoid tumor, granular cell tumor, other oncocytic tumors of bronchial origin and metastatic oncocytic tumors. Immunocytochemistry and electron microscopy confirmed the diagnosis of oncocytic carcinoid tumor. Conclusion Oncocytic carcinoid tumor of the lung has cytopathologic features similar to those of granular cell tumor and pulmonary oncocytoma. Immunocytochemistry, electron microscope or both are necessary to distinguish these neoplasms.

An immunohistochemical study to demonstrate oncocytes in nongonadotrophic pituitary adenomas was performed. The adenomas were 10 prolactinomas, 2 ACTH-producing adenomas (ACTHomas), and 28 growth hormone-producing adenomas (GHomas); we also studied 5 pituitary oncocytomas. GHomas were divided into two groups: GHomas with (GHomas-1) and without (GHomas-2) fibrous bodies. A small number of solitary large cells showed intense cytoplasmic granular reactivity for mitochondrial protein and cytochrome oxidase, resembling oncocytes in oncocytomas. The proportions of the mitochondrial protein-positive cells ranged from zero to 2.1% (0.3±0.4%). They were more frequent in GHomas, GHomas-1 in particular, than other types of adenomas (P

Background Hurthle cell carcinoma of the thyroid is a variant of follicular carcinoma, which has been considered by many as a more aggressive disease than the usual well-differentiated carcinoma of the thyroid. Others, however, have found Hurthle cell carcinoma to be a low-grade malignancy with little morbidity or mortality. Methods This is a retrospective report on all patients with Hurthle cell carcinoma diagnosed during the years 1951–1997 by the authors. The behavior of the disease and results of treatment were analyzed biostatistically and the outcome was compared with that of patients with pure follicular carcinoma treated during the same period. Results Forty-two patients were diagnosed with Hurthle cell carcinoma and 153 with follicular carcinoma during this period (2.8% and 10.3% of all differentiated carcinomas of the thyroid, respectively). The rate of local recurrence and disease-related mortality were both 9.5%, compared with 3.2% & 15.7%, respectively, for the follicular cancers. There was a trend for better outcome in patients younger than 55 years of age, in patients with tumors under 4 cm in size, and in patients treated by total thyroidectomy. Distant metastases occurred in four patients (9.5%) and were the cause of disease-related mortality in three. Conclusions When treated assertively, Hurthle cell carcinoma of the thyroid, an oncocytic variant of follicular carcinoma, has a favorable outcome, similar to that of pure follicular carcinoma. Uniting those two entities in a future classification and reporting should be considered. © 1999 John Wiley & Sons, Inc. Head Neck 21: 506–511, 1999.

To analyze relevant factors of neoplastic transformation in oncocytic neoplasms of the thyroid, expression of p53, Ki-67, and bcl-2 has been studied in oncocytic carcinomas (n = 17) and compared with results obtained in oncocytic adenomas (n = 20). P53 protein accumulation was found immunohistochemically in 75% of the oncocytic adenomas (15 of 20) and 88% of the oncocytic carcinomas (15 of 17). Eight of 17 of the carcinomas (47%), but only 3 of the 20 adenomas (15%), showed nuclear p53 accumulation in more than 10% of the cells, mostly in a focal pattern. Ki-67 expression also differed significantly between adenomas and carcinomas. The median of Ki-67-positive cells was 12/10 high-power fields (HPF) for adenomas and 76/10 HPF for carcinomas (P < .001). Furthermore, metastatic carcinomas had a significantly higher Ki-67 positivity than nonmetastasized carcinomas (164/10 HPF v 42/10 HPF, P < .05). Bcl-2 immunohistochemistry showed a constantly positive reaction in normal thyroid tissue. In contrast, bcl-2 protein was not detected in most of the adenomas (70%) and carcinomas (76%). In conclusion, p53 protein and Ki-67 is more prevalent in oncocytic carcinomas than in oncocytic adenomas of the thyroid, indicating that these factors may be involved in the progression of oncocytic neoplasms in the thyroid. In contrast, loss of bcl-2 appears to be an early event in the formation of oncocytic neoplasms of the thyroid. Its importance for malignant transformation is, however, unclear.

Two parotid mucoepidermoid carcinomas with predominant oncocytic features were initially assessed on frozen section. Because of extensive oncocytic change, it was inferred that the lesions were most likely benign. Permanent sections revealed low-grade mucoepidermoid carcinoma with prominent oncocytic change (in more than 75% of the neoplasms) in both cases. Review of 48 additional consecutive cases of mucoepidermoid carcinoma of the salivary glands revealed prominent oncocytic change (accounting for 60% of the neoplasm) in one high-grade lesion. Phosphotungstic acid-hematoxylin stains revealed strong granular cytoplasmic staining in the oncocytic elements; immunohistochemical stains for antimitochondrial antibodies also showed intense immunoreactivity in these cells. Oncocytic change is not typically a prominent feature of mucoepidermoid carcinoma of the salivary glands, and to our knowledge, only three such cases have been reported previously. Because most salivary gland lesions with oncocytic change are benign, it is important to distinguish mucoepidermoid carcinoma from other entities that may show prominent oncocytic change. We report three additional examples of this rare lesion, two low-grade tumors and one high-grade tumor, and review our experience with oncocytic change in mucoepidermoid carcinoma of the salivary glands.

Endometrial oncocytic carcinoma is an unusual neoplasm, with few cases reported. Endometrial curettage specimens coded as prominent oxyphilic metaplasia (N = 5) and oxyphilic or oncocytic carcinoma (N = 4) were reviewed, and hysterectomy slides from the four carcinomas were also examined. Immunohistochemical and ultrastructural analyses were performed in three of five metaplasias and in all four carcinomas. Most patients (89%) with oncocytic metaplasia and carcinoma had vaginal bleeding. Oncocytic metaplasia was characterized by a single layer of cells with abundant eosinophilic, granular cytoplasm, minimal pleomorphism, and rare mitotic activity. Carcinoma was diagnosed on the basis of an altered stroma (n = 2) and/or a confluent growth pattern (n = 4) and had a papillary (n = 4), glandular (n = 2), or solid (n = 1) morphology. Carcinomas showed a similar population of oncocytic cells as metaplasias, but with occasional nuclear stratification and greater pleomorphism and mitotic activity. Tumors were International Federation of Gynecology and Obstetrics (FIGO) grade 1 (n = 2) or 2 (n = 2) and FIGO stage Ib, Ic, IIb, and IIIc. Omental metastases developed in the patient with the stage III tumor at 13 months; the two patients with stage I tumors were alive with no evidence of disease at a mean of 29 months. All carcinomas expressed p53 and 75% and 100% were estrogen receptor (ER)- and progesterone receptor (PR)-negative, respectively, whereas all metaplasias were p53 negative- and ER- and PR-positive. Ki-67 labeling index was 1 to 3% in metaplasias and 14 to 33% in carcinomas. Oncocytic metaplasias and carcinomas contained abundant mitochondria and free ribosomes, accounting for the oncocytic appearance. Because oncocytic carcinomas frequently show deep myometrial invasion and require surgical staging, it is important to distinguish oncocytic metaplasia from carcinoma on biopsy material. Ki-67, p53, and ER and PR immunostains may assist in this potentially difficult differential.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hurthle cell adenomas (7 cases), Hurthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and >90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P

Background: Follicular thyroid cancer is a heterogeneous disease including follicular and Hurthle cell and tumors with and without vascular and major capsular invasion. Analyses of prognosis and risk groups have been criticized for not taking these differences into account. Methods: Retrospective analysis was done of 240 patients treated from 1940 to 1997. Results: Ninety-two patients without vascular or major capsular invasion followed up for a median of 14 years had no recurrences or deaths. In the remaining 148 patients, 32 had Hurthle cell and 116 had follicular cell carcinoma. Patients with Hurthle cell carcinoma were significantly older (55 vs 47 years; P = .0014). Lymphatic metastases did not influence outcome. Patients who were at high risk by age and sex, metastases, extent, and size had a 20-year survival rate of 36% for follicular and 35% for Hurthle cell carcinoma; patients at low risk had 20-year survival rates of 94% and 89%, respectively, with no significant difference between follicular and Hurthle cell carcinoma. Recurrences were treated successfully in 33% of patients with follicular carcinoma but never cured in patients with Hurthle cell carcinoma. Bilateral versus unilateral operation or radioiodine for ablation did not alter outcome. Conclusions: Follicular and Hurthle cell carcinoma with minimal capsular invasion behaved benignly. Age and sex, metastases, extent, and size risk criteria differentiate strongly between patients with high-risk and low-risk follicular and Hurthle cell carcinoma. Controlling for risk factors, Hurthle cell and follicular cell carcinomas have similar prognoses. (Surgery 1998;124:967-74.)

An oncocytic carcinoma of the submandibular gland diagnosed by fine-needle aspiration is reported. Cytologically, the tumor cells occurred singly, in three-dimensional clusters and in multilayered sheets. The cells had round-to-oval, centrally or eccentrically located nuclei with fine chromatin and prominent nucleoli. Many cells contained abundant granular cytoplasm and well-defined cell borders; however, several stripped nuclei with prominent nucleoli were also noted in the background. Follow-up histologic examination showed tumor cells arising from right submandibular gland and metastasizing to six of 14 cervical lymph nodes. Ultrastructural study demonstrated tumor cells packed with mitochondria in the cytoplasm. The patient was alive with no evidence of disease 6 months after the surgery.

A 37-year-old white male with a large pancreatic mass was referred to our institution with a hypodense liver lesion detected on CT scan. A fine-needle aspiration (FNA) was performed on the liver lesion. Diff-Quik smears demonstrated scattered papillary structures and single neoplastic cells with abundant well-defined dense granular cytoplasm. Eccentrically located nuclei were noted with single prominent nucleoli. Cell block preparations showed papillary structures lined by cells with abundant pink granular cytoplasm, hyperchromatic nuclei, and prominent single nucleoli. Electron microscopic examination displayed numerous but poorly preserved mitochondria. The diagnosis of papillary carcinoma with oncocytic features was made. Only two previous cases of pancreatic oncocytic tumors diagnosed by FNA have been reported in the literature. We present an additional case, notable in that the diagnosis was made in a metastatic liver nodule.

Oxyphilic hepatocytes, also called hepatic oncocytes, have been found in 20 of 47 cirrhotic livers (42%) with defects of the respiratory chain. Immunohistochemical studies using antisera against cytochrome-c-oxidase (complex IV) revealed respiratory chain-deficient oxyphilic foci in 16 of the 20 cases (75%). Fourteen percent of the oxyphilic areas were deficient, whereas only 8.5% of the nonoxyphilic liver nodules showed respiratory chain defects (P < 0.004). In addition, oxyphilic foci made up about 18% of all defective areas but were present in only 11.5% of the regenerative nodules. These results illustrate that oxyphilic cell change is associated with a higher propensity for the development of respiratory chain defects, but is not obligatory for this.

OBJECTIVE: To determine if any preoperative or intraoperative factors can reliably predict malignancy in patients with Hürthle cell neoplasms. SUMMARY BACKGROUND DATA: Most experienced surgeons recommend total thyroidectomy for Hürthle cell carcinomas and reserve thyroid lobectomy for Hürthle cell adenomas. However, delineation between Hürthle cell adenoma versus carcinoma often cannot reliably be made either before or during surgery. METHODS: Medical records from 57 consecutive patients who underwent thyroid resections for Hürthle cell neoplasms between October 1984 and April 1995 at The Johns Hopkins Hospital were analyzed to determine if any factors were predictive of malignancy. RESULTS: Of the 57 patients with Hürthle cell neoplasms, 37 had adenomas and 20 had carcinomas, resulting in a 35% prevalence of malignancy. Patients with adenomas did not differ from those with carcinoma with respect to age, sex, or history of head and neck irradiation. However, patients with Hürthle cell carcinomas had significantly larger tumors (4.0 +/- 0.4 cm vs. 2.4 +/- 0.2 cm, p < 0.005). Furthermore, although the incidence of malignancy was only 17% for tumors 1 cm or less and 23% for tumors 1 to 4 cm, tumors 4 cm or greater were malignant 65% of the time (p < 0.05). Both fine-needle aspiration and intraoperative frozen section analysis had low sensitivities in the detection of cancer (16% and 23%, respectively). With up to 9 years of follow-up, there has been no tumor-related mortality. CONCLUSIONS: These data demonstrate that the size of a Hürthle cell neoplasm is predictive of malignancy. Therefore, at the time of initial exploration for large Hürthle cell neoplasms (>4 cm), definitive resection involving both thyroid lobes should be considered because of the higher probability of malignancy.

Morphological similarities between renal oncocytomas and 'oncocytic' renal cell carcinomas (RCCs) make a differential diagnosis in many cases difficult. A series of 41 renal oncocytomas has been analysed by microsatellite markers from chromosomes 1, 2, 3p, 6q, 8p, 9, 10, 13q, 14q, 17, and 21, alterations of which are known to be involved specifically in non-papillary and chromophobe RCCs. Only eight of the 41 renal oncocytomas showed loss of heterozygosity (LOH). LOH at chromosomes 1 and 14 occurred in four tumours each and at chromosomes 2, 8, and 9 in one tumour each. Combined LOH at chromosomes 1, 9, and 14 and also at chromosomes 1 and 14 occurred in one case each. No LOH was seen at any other genomic sites. The lack of combination of LOH at specific chromosomal sites differentiates renal oncocytomas from other renal cell tumours with overlapping phenotypes. Applying the microsatellite assay described here, the diagnosis can be established within 2 days, from fresh as well as from paraffin-embedded material.

We reviewed 954 primary nonurothelial epithelial renal neoplasms with primary resection at Memorial Sloan-Kettering Cancer Center between the years 1980 and 1995 and classified 70 cases (7%) as renal oncocytomas. The study population was composed of 39 men and 31 women, and the mean age was 65 years (range 25 to 86 years). Fifty-six patients (80%) were asymptomatic at presentation, six (4%) had flank pain, six (4%) presented with a mass, and two (3%) had hematuria. Sixty-one were treated with total or radical nephrectomy, nine with partial nephrectomy. The right kidney was involved in 35 cases (50%), the left kidney in 32 (46%). Three cases (4%) were bilateral. Sixty-one cases (87%) were unifocal, nine (13%) multifocal. All the tumors were well circumscribed but unencapsulated. Forty-five (64%) were described as brown or red, whereas the remainder were variously described as tan to yellow. Central fibrosis or scar was described in 23 cases (33%), and gross areas of hemorrhage or cystic changes in 14 (20%). The mean size was 5.2 cm and median 5.0 cm (range 1.5 cm to 14 cm). Histologically, the tumors were characterized by a mixture of architectural patterns: compact cellular nests and acini embedded in a hyalinized, hypocellular stroma were present in 62 cases (89%), a solid nested architecture in 47 cases (67%), and a variable tubular component in 50 cases (71%). Small papillae, pseudopapillae, and intratubular epithelial tufts were seen in 19 cases (27%). Cytologically, the neoplasms also showed a mixture of cell types, the most common being the classic oncocyte, which consisted of round or polygonal cells with moderate to abundant granular, eosinophilic cytoplasm, and small round nuclei with evenly dispersed granular chromatin. Small basophilic nucleoli were visible in many of these cells in all cases. Thirty-one cases (44%) had a variable number of oncocytic cells with pyknotic nuclei and 20 (30%) contained clusters of small cells with a high nuclear/cytoplasmic ratio and dense hyperchromatic nuclei (so-called oncoblasts). Foci of tubules with clear cells embedded in a hyalinized stroma were present in six cases (9%). Cellular atypia was evident in 42 cases (60%) and was marked in 21 (30%). Eleven cases (16%) exhibited mitotic activity, albeit low. No case had atypical mitoses or necrosis. Twenty-two cases (31%) had areas of calcification within the hyalinized stroma, 12 (17%) had calcospherites, and three (4%) had osseous and myeloid metaplasia. Vascular invasion was present in three cases (4%), and invasion of perinephric fat in 14 (20%). One patient presented with liver metastasis. Fourteen cases (20%) were pT1, 42 (60%) pT2, and 14 (20%) pT3. After a mean follow-up of 58 months (range 1 to 181), 62 patients (89%) were alive with no evidence of tumor, six (9%) had died of other causes, one was alive with stable metastatic disease in the liver 58 months after diagnosis, and one died with metastatic disease to bone and liver. We conclude that renal oncocytomas have a varied morphologic appearance and their pathologic diagnosis should be based on a constellation of architectural and cytologic features. The overwhelming majority of cases behave in a benign fashion, although in rare instances they can metastasize. The presence of atypical morphologic features do not alter the excellent prognosis associated with oncocytomas and do not predict an aggressive clinical course.

BACKGROUND. Although nuclear grooves and inclusions are considered to be characteristic cytologic features of thyroid papillary carcinoma, a variety of other thyroid lesions may on occasion display these features in fine-needle aspiration specimens. METHODS. The authors evaluated the immunocytochemical staining of 16 fine-needle aspirations of thyroid papillary carcinoma and 14 aspirations of thyroid lesions confirmed to be other than papillary carcinoma but that included cells with nuclear grooving and/or inclusions, comprised of multinodular goiter (four cases), follicular adenoma (two cases), Hurthle cell adenoma (two cases), pure thyroiditis (three cases), and thyroiditis with nodular hyperplasia (three cases). CD44 previously has been shown to be selectively expressed in thyroid papillary carcinoma. RESULTS. Of 16 surgically confirmed cases of thyroid papillary carcinoma featuring nuclear grooves and inclusions on fine-needle aspiration, 14 (88%) stained intensely for CD44 in a membranous pattern. Of the 14 nonpapillary thyroid carcinoma cases, only 1 (7%), a Hurthle cell adenoma, featured membranous CD44 staining. The difference in the proportion of cases with CD44 staining between the two groups was statistically significant (chi-square test, P < 0.001). CONCLUSIONS. The authors conclude that immunostaining for CD44 can readily be performed on thyroid fine-needle aspiration specimens and that, for specimens featuring nuclear grooves and inclusions, the presence or absence of staining for CD44 may be of value in the distinction between thyroid papillary carcinoma and other lesions that may share some of the cytologic features of papillary carcinoma.

OBJECTIVE : To determine the value of computerized interactive morphometry in the preoperative prediction of malignancy in fine needle aspirates of Hurthle cell neoplasms. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven Hurthle cell adenomas (HCA) (n = 10) and Hurthle cell carcinomas (HCC) (n = 9) were studied by interactive computerized morphometry. The measured features included the areas, perimeters and shape factors of individual cells, nuclei and nucleoli; the nucleocytoplasmic and nucleolonuclear ratios; and the eccentricities of nuclei and nucleoli. RESULTS: Only nucleolar features showed statistically significant differences between HCA and HCC. These features were the nucleolar area and its standard deviation, the nucleolar form factor and circularity, and the nucleolonuclear ratio. The most effective, albeit imperfect, discrimination was achieved by the nucleolar form factor. CONCLUSION: Nucleolar features, such as size, variation in size and roundness, may be more effective than cellular or nuclear features I in differentiating between HCA and HCC in fine needle aspiration smears.

Introduction: Oncocytic neoplasms as tumors arising in the adrenal glands are rare, usually considered as nonfunctional and benign. In the current literature, there are extremely limited reports of adrenal oncocytic neoplasms; as to date, only 147 cases have been described. The rarity of the event prompted this study which reviews and presents the incidence, histology, diagnosis and therapy of adrenal oncocytic neoplasms. Materials and Methods: A review by systematic literature search was done using the MEDLINE®/Cochrane libraries from 1950 to date using the medical subject headings ‘oncocytoma', ‘adrenal gland', ‘adrenal oncocytoma', ‘adrenal oncocytic neoplasm' and ‘adrenal oncocytic carcinoma'. Results: Adrenal oncocytic neoplasm is a rare disease, usually incidentally detected because only 17% are functional adrenal masses. The typical oncocyte displays abundant granular eosinophilic cytoplasm, due to the accumulation of mitochondria. Computed tomography and magnetic resonance imaging are not able to identify or differentiate benign and malignant oncocytic neoplasms. The mainstay of therapy is adrenalectomy, recently performed by laparoscopy. The prognosis is good for benign tumors, while adrenocortical oncocytic carcinoma has a poor survival rate of only 5 years. Conclusions: Adrenal oncocytic neoplasm, a rare and mostly benign tumor, usually presents as an incidental, large adrenal mass; surgery is the mainstay of therapy, by means of laparoscopy which is now the most diffuse approach to adrenalectomy.

Background. Hurthle cell carcinomas of the thyroid are unusual variants of well-differentiated thyroid cancers. Considered more aggressive tumors, their optimal treatment is controversial. Our institution's half century of experience, the largest series to date, includes 40 patients with Hurthle cell carcinomas of 1000 well-differentiated thyroid cancers. Methods. A retrospective study was carried out on 40 patients. Results. Seventy-two percent were female, with a median age of 53 years. Median follow-up was 9 years. With the AMES risk stratification (age, distant metastasis, capsular extent, tumor size), among the 21 high-risk patients, 10 (48%) had a recurrence or died, with median time to recurrence 3 years (range, 0.5 to 14 years). Of these 10, 5 died of disease, one died of unrelated causes with disease, and 4 are alive with disease. Five recurrences presented as distant metastases. Extent at operation was the strongest predictor of recurrence, occurring in 66% of those with gross extraglandular involvement. Conclusions. The AMES criteria are useful in predicting recurrence and death. Although more aggressive surgery is appropriate for high-risk patients, in general their outlook remains grim.

We report on a morphologic variant of multiple myeloma, identified in a 39-year-old man, with osteolytic lesions in two ribs and three lumbar vertebrae. Serum electrophoresis was normal and immunofixation of serum and urine was negative. Histologic examination of a resected rib revealed a homogeneous population of neoplastic plasma cells with granular and eosinophilic cytoplasm. Immunohistochemical stains showed monoclonality for λ light chain and negativity for all heavy chains. At the ultrastructural level, the cytoplasm of the neoplastic plasma cells was almost totally occupied by round and elongated mitochondria, pushing the rough endoplasmic reticulum to the periphery. To the best of our knowledge, only two similar cases have been reported in the literature so far. The usefulness of obtaining a clinicopathologic correlation for the behaviour of this extremely rare variant of multiple myeloma is discussed.

BACKGROUND: Oncocytoma designates a usually benign tumor consisting of oncocytes (cells rich in mitochondria). Rarely do endocrine pancreatic tumors show oncocytic transformation, and consequently their liver metastases may resemble a hepatocellular carcinoma. CASES: Case 1. a 36-year-old male, presented with an 8-cm pancreatic mass with multiple liver metastases. Fine needle aspiration (FNA) biopsy was performed on the liver. The cytologic features were highly cellular material; numerous isolated cells and irregular, loose cellular aggregates; rare mitoses ; round or polygonal cell shape; rosette formation; and large, granular, eosinophilic cytoplasm (suggestive of poorly differentiated hepatocellular carcinoma). Case 2, a 57-year-old female with hypoglycemia, had a 13-cm pancreatic mass. FNA material showed the same cytologic features as case 1. In situ hybridization to detect albumin mRNA was negative in both cases, while immunocytologic reactions for glandular epithelial cytokeratin and chromogranin A were positive. Case 2 was also positive for insulin. CONCLUSION: Oncocytic transformation in endocrine tumors of the pancreas is a rare occurrence and must be kept in mind in the diagnostic workup of FNA material from tumors of the hepatopancreatic region.

症例は65歳男性. 検診で胸部X線上異常影が指摘され, 当院入院となった. 画像上, 右S4に2.8×2.2cmの境界明瞭な結節影が認められ, 経気管支生検にて乳頭状腺癌の診断が得られたため, 右中葉切除術を施行した. 肉眼所見上, 腫瘍の大部分は白色の粘液で占められ, 嚢胞様構造を呈していた. 光顕像では, 豊富な細胞外粘液中に, 小塊状の癌細胞が, 少数散在性に浮遊する像が認められ, 粘液結節性腺癌と診断した. 電顕的には腫瘍細胞のほとんどが多数の腫大したミトコンドリアで特徴づけられるoncocyte様の細胞であり, 気管支腺への分化が示唆された. 粘液結節性腺癌は, 細胞成分が少ないため術前診断が困難とされているが, 本例では腫瘍の中枢側に乳頭状腺癌の部分が認められ, 生検で同部が採取されたものと考えられた.

Oncocytic carcinomas are uncommon; they represent 11% of all oncocytic salivary gland neoplasms, 0.5% of all epithelial salivary gland malignancies and 0.18% of all epithelial salivary gland tumors. A 65-year-old woman was admitted to our ENT clinic with a history of a painless left preauricular mass. No lymph node was palpable on either side of her neck. Computed tomography demonstrated a 3 x 3-cm solid lesion in the left parotid gland. As oncocytes and atypical cells were seen at the cytologic examination of a fine-needle aspiration biopsy, this finding suggested a malignant epithelial tumor. Total parotidectomy by preserving the facial nerve was performed. The result of the pathologic examination was oncocytic carcinoma regarding histopathologic and immunohistochemical findings and especially the invasive growth pattern. We preferred a close follow-up to an elective neck dissection, and reserved the neck dissection for a recurrence. The prognosis of oncocytic carcinomas is not well known because of their low incidence. Further investigation of the prognosis of patients with oncocytic carcinoma of the parotid gland is warranted as more cases are reported.

Oncocytic carcinoma is an extremely rare malignancy of salivary glands accounting for 0.5% of all epithelial salivary gland malignancies and 0.18% of all epithelial salivary gland tumors. In 1894 Hurthle, a German pathologist first described oncocytes in thyroid glands of normal canine. The term ‘Oncocyte’ was coined by Hamperl in 1931. The oncocytic carcinoma represents 5% of all oncocytic salivary gland neoplasms and less than 1% of all salivary gland tumors. This case report describes a classical case of oncocytic carcinoma in 55 year old male patient. Keywords: Oncocytic carcinoma, Submandibular gland, Salivary gland neoplasm

Nodular dermatofibrosis is a rare condition of German Shepherd Dogs characterized by fibromatous nodules in the skin associated with multifocal renal neoplasia. Pedigree analyses of affected dogs indicates that the disorder may be inherited in an autosomal dominant att tern.^ In this report, we describe an unusual variant of renal carcinoma in nodular dermatofibrosis.

A case of small round and spindle cell sarcoma with neuronal differentiation and oncocyte-like features is presented. The tumor was encountered in a 32 year old Japanese woman with an initial presentation of palpable tumor in the left lateral region of the thorax. The resected tumor was a partially well encapsulated whitish medullary one and consisted of small round and spindle tumor cells, together with so-called rhabdoid cells in the small round cell area. Although pseudorosettes were often observed, true rosette formation could not be detected anywhere. Ultrastructurally, despite a histologic variety of tumor cells, most tumor cells possessed numerous mitochondria, some of which occasionally contained abnormal filamentous or crystalloid structures. Various amounts of microfilaments were present in most tumor cells and microtubules were present in a few. A minority of small round cells possessed a small number of neurosecretory granules, especially in short cytoplasmic processes. A positive immunoreaction for neuron specific enolase was found by immunohistochemical examination in several small round tumor cells and for neurofilaments in lesser numbers. Despite the lack of S-100 protein, MB2 was detected in both small round and spindle cells. On the basis of these findings, the tumor of the present case corresponds to malignant peripheral nerve sheath tumor with neuronal differentiation and oncocytic features.