Oncocytic Tumors Research Articles

Intraductal Oncocytic Papillary Neoplasms of the Pancreas.

Intraductal oncocytic papillary neoplasms (IOPNs) are cystic neoplasms with intraductal growth and complex papillae composed of oncocytic cells. IOPNs have been reported both in the pancreas and biliary tree, and are most likely closely related in these 2 locations. In the pancreas, these rare tumors are now considered 1 of the 4 histologic subtypes of intraductal papillary mucinous neoplasm (IPMN). Significant differences in histology, immunophenotype, and molecular genetics have been reported between IOPNs and other IPMN subtypes. However, there are limited data regarding the clinical behavior and prognosis of IOPNs in comparison to other subtypes of IPMN. We review features of pancreatic IOPNs and discuss the differential diagnosis of other intraductal lesions in the pancreas.

The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes

AbstractIn 2010, the World Health Organization reclassified the entity originally described as intraductal oncocytic papillary neoplasm as the ‘oncocytic subtype' of intraductal papillary mucinous neoplasm. Although several key molecular alterations of other intraductal papillary mucinous neoplasm subtypes have been discovered, including common mutations in KRAS, GNAS, and RNF3, those of oncocytic subtype have not been well characterized. We analyzed 11 pancreatic ‘oncocytic subtype' of intraductal papillary mucinous neoplasms. Nine pancreatic ‘oncocytic subtype' of intraductal papillary mucinous neoplasms uniformly exhibited typical entity-defining morphology of arborizing papillae lined by layers of cells with oncocytic cytoplasm, prominent, nucleoli, and intraepithelial lumina. The remaining two were atypical. One lacked the arborizing papilla and had flat oncocytic epithelium only; the other one had focal oncocytic epithelium in a background of predominantly intestinal subtype intraductal papillary mucinous neoplasm. Different components of this case were analyzed separately. Formalin-fixed, paraffin-embedded specimens of all cases were microdissected and subjected to high-depth-targeted next-generation sequencing for a panel of 300 key cancer-associated genes in a platform that enabled the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Fresh frozen specimens of two cases were also subjected to whole-genome sequencing. For the nine typical pancreatic ‘oncocytic subtype' of intraductal papillary mucinous neoplasms, the number of mutations per case, identified by next-generation sequencing, ranged from 1 to 10 (median=4). None of these cases had KRAS or GNAS mutations and only one had both RNF43 and PIK3R1 mutations. ARHGAP26, ASXL1, EPHA8, and ERBB4 genes were somatically altered in more than one of these typical ‘oncocytic subtype' of intraductal papillary mucinous neoplasms but not in the other two atypical ones. In the neoplasm with flat oncocytic epithelium, the only mutated gene was KRAS. All components of the intestinal subtype intraductal papillary mucinous neoplasms with focal oncocytic epithelium manifested TP53, GNAS, and RNF43 mutations. In conclusion, this study elucidates that ‘oncocytic subtype' of intraductal papillary mucinous neoplasm is not only morphologically distinct but also genetically distinct from other intraductal papillary mucinous neoplasm subtypes. Considering that now its biologic behavior is also being found to be different than other intraductal papillary mucinous neoplasm subtypes, ‘oncocytic subtype' of intraductal papillary mucinous neoplasm warrants being recognized separately.

Comprehensive Analysis of the Transcriptional and Mutational Landscape of Follicular and Papillary Thyroid Cancers.

Follicular thyroid carcinoma (FTC) and benign follicular adenoma (FA) are indistinguishable by preoperative diagnosis due to their similar histological features. Here we report the first RNA sequencing study of these tumors, with data for 30 minimally invasive FTCs (miFTCs) and 25 FAs. We also compared 77 classical papillary thyroid carcinomas (cPTCs) and 48 follicular variant of PTCs (FVPTCs) to observe the differences in their molecular properties. Mutations in H/K/NRAS, DICER1, EIF1AX, IDH1, PTEN, SOS1, and SPOP were identified in miFTC or FA. We identified a low frequency of fusion genes in miFTC (only one, PAX8–PPARG), but a high frequency of that in PTC (17.60%). The frequencies of BRAFV600E and H/K/NRAS mutations were substantially different in miFTC and cPTC, and those of FVPTC were intermediate between miFTC and cPTC. Gene expression analysis demonstrated three molecular subtypes regardless of their histological features, including Non–BRAF–Non–RAS (NBNR), as well as BRAF–like and RAS–like. The novel molecular subtype, NBNR, was associated with DICER1, EIF1AX, IDH1, PTEN, SOS1, SPOP, and PAX8–PPARG. The transcriptome of miFTC or encapsulated FVPTC was indistinguishable from that of FA, providing a molecular explanation for the similarly indolent behavior of these tumors. We identified upregulation of genes that are related to mitochondrial biogenesis including ESRRA and PPARGC1A in oncocytic follicular thyroid neoplasm. Arm-level copy number variations were correlated to histological and molecular characteristics. These results expanded the current molecular understanding of thyroid cancer and may lead to new diagnostic and therapeutic approaches to the disease.

Diagnostic utility of vimentin, CD117, cytokeratin-7 and caveolin-1 in differentiation between clear cell renal cell carcinoma, chromophobe renal cell carcinoma and oncocytoma

Overlapping morphological characteristics pose some difficulties in making a proper diagnosis of clear cell renal cell carcinoma (CCRCC), chromophobe renal cell carcinoma (ChRCC), and oncocytoma, on the basis of hematoxylin–eosin-stained tissue sections. Our objective was to find out a fast, reliable panel of immunohistochemical markers for differentiation between them. The study was carried out on 55 selected renal tumor specimens: 36 cases of CCRCC, seven cases of ChRCC, and 12 cases of oncocytoma. The specimens were stained immunohistochemically for vimentin, CD117, cytokeratin (CK)7, and caveolin (Cav)-1. Sensitivity and specificity for each marker were calculated. Vimentin expression was exclusively observed in CCRCC (100%) and negative in ChRCC and oncocytoma. CD117 was absent in CCRCC, but it was strongly expressed in ChRCC (85.5%) and oncocytoma (91.7%), with high sensitivity and specificity. Most CCRCCs and oncocytomas were negative for CK7 (91.7% and 83.3%, respectively), in contrast to ChRCCs, which showed positivity in nearly 86% of the cases. Good sensitivity and specificity were calculated for CK7 in differentiating studied oncocytic tumors. Cav-1 was positive in ∼78% of the CCRCCs and in all ChRCCs, whereas the vast majority of oncocytomas were negative. So the immunoprofile of CCRCC was vimentin+/CD117−/CK7−/Cav-1±, ChRCC was vimentin−/CD117+/CK7+/Cav-1+, and oncocytoma was vimentin−/CD117+/CK7±/Cav-1−. So, by using combination of four markers (vimentin, CD117, CK7, and Cav-1), we achieved excellent sensitivity and specificity for differential diagnosis of CCRCC, ChRCC and oncocytoma.

Vanishing thyroid gland tumors: Infarction as consequence of FNA?

Fine-needle aspiration (FNA)-induced secondary changes were described in various organs. Complete replacement of tumor by necrosis causes diagnostic and management problems. Seven cases of totally or partially vanished thyroid lesions were identified from the archive of Department of Pathology, Fimlab Laboratories within 5year period. Histopathological slides were revised in all cases. Total thyroidectomy or lobectomy samples were from 4 females and 3 males patients aged 37-83 years (mean 67.1 years). Imaging data were available in 6 cases. Cytology slides and data were available only in 3 cases: two revealed follicular neoplasm and one was insufficient according to Bethesda system. In 5 cases, final histopathology revealed total necrosis of the lesion with only one case with available cytological diagnosis of oncocytic follicular neoplasm. In remaining 2 cases, replacement by necrosis was partial. Of note, in three cases, oncocytic metaplasia was present. Total histopathological blocking with thorough check of capsular areas is recommended in necrotic tumors. Vanishing thyroid lesion phenomenon is rare, but in cases of disappearance of tumor, preoperative cytology diagnosis is the only clue for the patient management. Diagn. Cytopathol. 2016;44:568-573. © 2016 Wiley Periodicals, Inc.

Categorizing renal oncocytic neoplasms on core needle biopsy: a morphologic and immunophenotypic study of 144 cases with clinical follow-up

There is limited literature on renal oncocytic neoplasms diagnosed on core biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were retrospectively reviewed. Morphologic features and an immunohistochemical panel of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis, statistical analysis including a random forest classification, and follow-up were recorded. The post-immunohistochemical diagnoses of 144 renal oncocytic core biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and cannot exclude RCC (21%). Diagnosis was revised following immunohistochemistry in 7% of cases. The most common features for oncocytoma (excluding dense granular cytoplasm) were nested architecture, edematous stroma, binucleation and tubular architecture; the most common features for favor RCC were sheet-like architecture, nuclear pleomorphism, papillary architecture, and prominent cell borders. High nuclear grade, necrosis, extensive papillary architecture, raisinoid nuclei, and frequent mitoses were not seen in oncocytomas. Comparing the pathologist and random forest classification, the overall out-of-bag estimate of classification error dropped from 23% to 13% when favor RCC and cannot exclude RCC were combined into 1 category. Resection was performed in 19% (28 cases) with a 94% concordance (100% of favor RCC biopsies and 90% of cannot exclude RCC biopsies confirmed as RCC; 83% of favor oncocytomas confirmed); ablation in 23%; and surveillance in 46%. Follow-up was available in 92% (median follow-up, 33months) with no adverse outcomes. Renal oncocytic neoplasms comprise a significant subset (16%) of all core biopsies, and the majority (78%) can be classified as favor oncocytoma or favor RCC.

Virilizing oncocytic adrenocortical carcinoma: clinical and immunohistochemical studies

Context: Oncocytic tumors of the adrenal cortex are rare, mostly nonfunctioning and benign.Setting: Report virilizing oncocytic adrenocortical carcinoma in a 50-year-old woman.Patient: She presented a recent and progressive virilization syndrome, associated with high blood pressure. Hormonal evaluation showed elevated serum testosterone and delta-4-androstenedione levels, normal urinary free cortisol level and incomplete suppression of cortisol at the 1 mg dexamethasone suppression test. CT scan of the abdomen revealed a 35 mm left adrenal mass.Intervention: The patient underwent a left adrenalectomy, and the histological study showed a 3 cm oncocytic adrenocortical carcinoma with signs of malignancy.Results: Immunohistochemical study revealed that tumor cells expressed the steroidogenic enzymes involved into androgen synthesis (3βHSD and P450c17α), P450 aromatase and luteinizing hormone (LH) receptors. Post-operatively, signs of virilization improved rapidly, serum testosterone and delta-4-androstenedione levels returned to normal, as did the dexamethasone suppression test. During follow-up CT-scan and 18-FDG PET/CT showed a right ovary mass, corresponding to a follicular cyst associated with hyperthecosis. The patient is alive with no recurrence 48 months after adrenal surgery.Conclusion: Oncocytic adrenocortical carcinomas, although extremely rare, should be considered in women with a virilization syndrome. In this woman immunohistochimical studies revealed the presence of steroidogenic enzymes involved into androgen synthesis and aromatization, and LH receptors could be implicated in this pathology.

Effect of Stereotactic Body Radiotherapy on the Growth Kinetics and Enhancement Pattern of Primary Renal Tumors.

The objective of our study was to assess the growth rate and enhancement of renal masses before and after treatment with stereotactic body radiotherapy (SBRT). This retrospective study included all patients with renal masses who underwent SBRT during a 5-year period. Orthogonal measurements of renal masses were obtained on pre- and posttreatment CT or MRI. Pre- and posttreatment growth rates were compared for renal mass diameter and volume using the t test. Pre- and posttreatment tumor enhancement values were compared for tumors that underwent multiphasic contrast-enhanced MRI. Forty patients underwent SBRT for the treatment of 41 renal tumors: clear cell renal cell carcinomas (RCCs) (n = 16), papillary RCCs (n = 6), oncocytic neoplasms (n = 8), unclassified RCCs (n = 2), urothelial carcinoma (n = 1), and no pathologic diagnosis (n = 8). The mean maximum tumor diameter before treatment was 3.9 cm (range, 1.6-8.3 cm). Three hundred thirty-eight pre- and posttreatment imaging studies were analyzed: 214 MRI studies and 124 CT studies. The mean pre- and posttreatment lengths of observation were 416 days (range, 2-1800 days) and 561 days (83-1366 days), respectively. The mean pretreatment tumor growth rate of 0.68 cm/y decreased to -0.37 cm/y post treatment (p < 0.0001), and the mean tumor volume growth rate of 21.2 cm(3)/y before treatment decreased to -5.35 cm(3)/y after treatment (p = 0.002). Local control-defined as less than 5 mm of growth-was achieved in 38 of 41 (92.7%) tumors. The Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 showed progression in one tumor (2.4%), stability in 31 tumors (75.6%), partial response in eight tumors (19.5%), and complete response in one tumor (2.4%). No statistically significant change in tumor enhancement was shown (mean follow-up, 142 days; range, 7-581 days). Renal tumors treated with SBRT show statistically significant reductions in growth rate and tumor size after treatment but do not show statistically significant differences in enhancement in the initial (mean, 142 days) posttreatment period.

Malignancy risk of oncocytic changes in thyroid nodules: who should we offer surgery to?

Background Oncocytic (Hürthle) cell in fine-needle aspiration biopsy (FNAB) remains challenging for surgeons. Surgical treatment is recommended for oncocytic change in FNAB, since it can sometimes be a struggle to determine the nature of thyroid nodules. We aimed to investigate the clinical significance of oncocytic changes in FNAB in terms of management of patients.Methods The FNAB samples of 172 patients with thyroid nodules were reviewed. Of these, 39 patients with cytologic findings of oncocytic changes on FNAB [POC: predominance of oncocytic cells; SFON-H: suspicious for follicular or oncocytic neoplasm (Hürthle cell type), SM-O: suspicious for malignancy-papillary or follicular carcinoma; oncocytic variant)] were included.Results FNAB demonstrated POC in 14 (35.8%), SFON-H in 15 (38.4%), and SM-O in 10 (25.6%) patients. The overall malignancy rate was 35.8% (n = 14). Clinical and laboratory data were not found to be associated with thyroid cancer while nodule size was significantly higher in patients with thyroid malignancy (15.2 versus 23.3 mm, p = 0.032). Regarding FNAB results including oncocytic changes, the rate of malignancy was significantly different and almost three-fold higher in nodules classified as SFON-H and SM-O [48% versus 14.2% with POC, p = 0.044]. Besides, there was a positive correlation between SFON-H and SM-O cytology and malignancy (p = 0.036, r = 0.337).Conclusions It is hard to discern the significance of oncocytic changes in FNAB report and to determine an optimal approach as a surgeon. We recommend surgery for the patients with an FNAB showing SFON-H and SM-O whereas POC should be better to be followed-up.

Renal clear cell carcinoma metastasis to salivary glands - a series of 9 cases: clinico-pathological study.

Metastatic tumors involving salivary glands arising from the non-head and neck area are very rare. Renal cell carcinoma (RCC) is known for its high propensity for metastasis to unusual localizations. RCC metastasis to the maxillofacial area is an uncommon event (16%), but metastasis to salivary glands is extremely rare. We report a series of 9 such cases retrieved from two institutions. The group included 6 females and 3 males. The age at diagnosis ranged from 60 to 97 years (mean 72.6 years). The tumors involved the parotid gland in 7 cases, and the submandibular and small salivary gland of the oral cavity in 1 case each. The size of tumors ranged from 0.4 to 5 cm. Total parotidectomy with selective neck dissection was performed in 4 cases, while superficial parotidectomy was performed in 1 case and simple resection in 3 cases. Histologically, all the tumors were clear cell renal cell carcinomas, and therefore the differential diagnosis mainly included clear cell variants of salivary gland carcinomas. The parotid gland was the initial manifestation of renal malignancy in 4 of the cases, while in the remaining 5 cases a history of RCC had been known. The salivary gland involvement developed from 11 months to 13 years after the time of diagnosis of the primary tumor. In 2 cases it was the first site of dissemination. Pathologists need to maintain a high index of suspicion for the possibility of metastasis when confronted with oncocytic or clear cell neoplasms developing in salivary glands. RCC, although rare, should be included in this differential diagnosis.

Oncocytic carcinoma of Submandibular gland-A case report

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

The Significance of BerEp4 and Cytokeratin 19 Expressions in Epithelial Tumors of Kidney and Renal Pelvis

Objective: The differential diagnosis in the epithelial tumors of kidney and renal pelvis can be problematic due to their overlapping morphologic features. This is much more complicated in some conditions, such as renal oncocytoma (RO) vs chromophobe renal cell carcinoma (ChRCC) and renal cell carcinoma (RCC) vs urothelial carcinoma of renal pelvis (UC-RP). The purpose of this study was to assess potential contributions of BerEP4 and cytokeratin 19 (CK19) expressions in the differential diagnosis of these challenging cases. Methods: A total 57 cases consisted of 11 chromophobe (ChRCC), 18 clear cell (CCRCC), 12 papillary (PRCC), and 2 unclassified RCCs, 1 multilocular cystic renal cell neoplasm (MCRCN) with low malignant potential, 7 UC-RP, and 6 renal oncocytomas (RO) were stained against BerEp4 and CK19 antibodies using automated immunostainer. Results: All ROs demonstrated membranous BerEP4 expression, but no CK19 expression. Unlike ROs, most ChRCCs exhibited diffuse and strong CK19 expression, but no or focal and weak BerEP4 expression. This distinctive opposite expression pattern was highlighted in hybrid oncocytic chromophobe tumor (HOCT). CCRCCs showed highly variable expression patterns for both markers. PRCC type 1 tumors demonstrated diffuse and strong BerEp4 and CK19 expressions. PRCC type 2 exhibited BerEP4 and CK19 expressions, but their expressions were focal and weaker than for PRCC type 1. MCRCN demonstrated diffuse and strong BerEP4 expression, but no expression for CK19 unlike cystic CCRCC, which is strongly positive for both markers. Epithelioid cells in unclassified RCC showed strong CK19 and weak BerEP4 expression, whereas spindle cells in the tumor did not express CK19 and BerEp4 or exhibited scattered and weak expressions. UC-RP showed diffuse and strong CK19 expression, but no or scattered BerEP4expression was seen in the tumor. We also evaluated CK19 and BerEP4 expression in non-neoplastic adjacent kidney and renal pelvis. Conclusion: This study revealed that 1) BerEP4 and CK19 exhibit variable and distinctive immunoprofiles in epithelial tumors of kidney and renal pelvis, 2) an immunoprofile of BerEP4 (+)/CK19 (-) favors RO in contrast to an opposite profile for ChRCC, 3) The heterogeneous expressions of BerEP4 and CK19 in low grade RCC with eosinophilic cytoplasm favors HOCT, 4) PRCC type 1 strongly express both biomarkers, and 5) although RCC subtypes express CK19 in a variable proportion and intensity, diffuse and strong CK19 expression favors UC-RP.

Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm

Adrenocortical oncocytic neoplasms (oncocytomas) are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol) and androgens (androstenedione and DHEAS), a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing's syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline) according to the Lin-Weiss-Bisceglia criteria.

Renal oncocytosis: a clinicopathological and cytogenetic study of 42 tumours occurring in 11 patients

Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively.

Variants in mitochondrial tRNA gene may not be associated with thyroid carcinoma.

Thyroid cancer is a very common form of endocrine system malignancy. To date, the molecular mechanism underlying thyroid cancer remains poorly understood. Studies of oncocytic tumors have led to a hypothesis which proposes that defects in oxidative phosphorylation (OX- PHOS) may result in a compensatory increase in mitochondrial replication and gene expression. As a result, mitochondrial DNA (mtDNA) mutation analysis has become a useful tool to explore the molecular basis of this disease. Among these mutations, mitochondrial transfer RNAs (mttRNAs) are the hot spots for pathogenic mutations associated with thyroid cancer. However, due to its high mutation rate, the role of mt-tRNA variants in thyroid cancer is still controversial. To address this problem, in this study, we reassessed seven reported mt-tRNA variants: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C, in clinical manifestations of thyroid cancer. We first performed the phylogenetic conservation analysis for these variants; moreover, we used a bioinformatic tool to compare the minimum free energy (G) of mt-tRNA with and without mutations. Most strikingly, none of these variants caused the significant change of the G between the wild-type and the mutant form, suggesting that they may not play an important roles in thyroid cancer. In addition, we screened the frequency of the “pathogenic” A12308G alternation in 300 patients with thyroid cancer and 200 healthy controls. We found that there were five patients and three control subjects carrying this variant. It seemed that the A12308G variant may be a common polymorphism in the human population. Taken together, our study indicated that variants in mt-tRNA genes may not play active roles in patients with thyroid cancer.

Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

Clinical Implications of Accurate Cytologic Diagnosis of Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas

Clinical Implications of Accurate Cytologic Diagnosis of Oncocytic Type Intraductal Papillary Mucinous Neoplasm of the Pancreas

Utility of SOX10 in Diagnosing Salivary Gland Oncocytic Tumors in Fine Needle Aspiration Cell Blocks

SOX10 is a transcription factor expressed from the developmental stage to adulthood in acinar and intercalated ducts of major salivary glands, and in some salivary gland tumors. Its role in cytologic specimens has been rarely documented. This study was performed to evaluate its utility in the diagnosis of salivary gland oncocytic tumors on fine …

Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: Criteria and clinical implications of accurate diagnosis.

Cytologic findings of pancreatic oncocytic-type intraductal papillary mucinous neoplasms (IPMNs)/intraductal oncocytic papillary neoplasms (IOPNs) are largely unknown. Five IOPNs encountered by the authors were analyzed. Four IOPNs were located in the pancreatic head, and 1 was located in the pancreatic body/tail in 2 men and 3 women ages 56 to 84 years (mean age, 66 years). Radiologic diagnoses included pancreatic ductal adenocarcinoma (PDAC) in 2 patients, invasive cancer associated with IPMN in 1 patient, IPMN versus mucinous cystic neoplasm in 1 patient, and cystic mass in 1 patient. Cytologic findings included: hypercellular smears (4 of 5 cases) containing well formed clusters of oncocytic cells (5 of 5 cases) with prominent, slightly eccentric nucleoli (4 of 5 cases), predominantly arranged in sheets/papillary units (5 of 5 cases), with punched-out intercytoplasmic spaces (4 of 5 cases), and with occasional 3-dimensional groups and focal necrosis (3 of 5 cases). The intracytoplasmic mucin and thick extracellular mucin typical of other IPMNs were observed only in 2 cases and were very limited. The mean size on resection was 4.5 cm. Invasion was observed in 3 cases (0.1, 0.3, and 2.0 cm) of tubular-type IPMN. Initial cytologic evaluation was performed by the authors in 4 of 5 cases, which were diagnosed as IOPN (n = 3) and IPMN versus cystic PDAC (n = 1). One case was initially misdiagnosed as PDAC and, on resection, proved to be noninvasive IOPN. Cytologic features of IOPNs are classical, similar to their histologic counterparts, and differ significantly from other IPMN subtypes. Because of their highly complex appearance, they are often radiologically misdiagnosed as PDAC; thus, failure to recognize their characteristic features on fine-needle aspiration may lead to inappropriate treatment. Patients with IOPN have an incomparably better prognosis than patients with ordinary PDAC, even when their neoplasms are invasive.

Active Surveillance for Renal Neoplasms with Oncocytic Features is Safe

Oncocytomas are benign tumors often diagnosed incidentally on imaging. Small case series have suggested that the growth kinetics of oncocytomas are similar to those of malignant renal tumors. Biopsy material may be insufficient to exclude a diagnosis of chromophobe renal cell carcinoma. We evaluated and compared the growth rates of oncocytoma and chromophobe renal cell carcinoma to improve our understanding of their natural history. This was a single center, retrospective study of patients diagnosed with lesions suggestive of oncocytoma or chromophobe renal cell carcinoma between 2003 and 2014. The growth rates were estimated using a mixed effect linear model. Patient and lesion characteristics were tested using a similar model for association with growth rate. Of the 95 lesions (oncocytoma 81, chromophobe renal cell carcinoma 14) included in the analysis 98% were diagnosed on biopsy. The annual growth rate was 0.14 cm and 0.38 cm for oncocytoma (median followup 34 months) and chromophobe renal cell carcinoma (median followup 25 months), respectively (p=0.5). Baseline lesion size was significantly associated with growth (p <0.001). The majority of oncocytomas (74%) and chromophobe renal cell carcinomas (67%) followed up to the 3-year mark had grown. Of these, 8 underwent surgery (6 in the chromophobe renal cell carcinoma group). The initial diagnosis was confirmed in all. Overall 5 patients died, all of nonrenal related causes. Although the majority of oncocytic renal neoplasms will grow with time, surveillance appears to remain safe. Patients opting for this strategy should be made aware that a diagnosis of oncocytoma following biopsy is associated with some degree of uncertainty due to the difficulty of differentiating them from other oncocytic renal neoplasms.