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Objective: The classification of renal tumors is expanding with the addition of new molecular entities in the 5th World Health Organization classification. Apart from this, the major updates in the definition of papillary renal cell carcinoma are that these tumors are no longer subtyped into type 1 and type 2. In oncocytic tumors, the new molecularly defined renal tumors, emerging and novel entities need to be considered in the diagnosis of oncocytic and chromophobe renal tumors., Material and Methods: This is a retrospective study to review and reclassify papillary, oncocytic, and chromophobe renal tumors based on the new WHO classification and correlate with clinical data, gross, microscopic features, and immunohistochemistry markers., Results: A total of thirteen cases were reviewed and the tumor grade was changed for three out of four cases of papillary renal cell carcinoma and a single case was recategorized and graded. In nine cases of oncocytic and chromophobe renal tumors, the diagnoses were modified in 3 cases., Conclusion: Newly defined molecular renal tumors require advanced immunohistochemistry markers and molecular tests. This poses diagnostic challenges to pathologists practicing in low resource settings where molecular tests are not available.

Low-grade oncocytic tumor of the kidney (LOT) is characterized by cytoplasmic eosinophilia and a CK7-positive/CD117-negative immunophenotype. Morphologically, they exhibit overlapping features with oncocytoma and chromophobe renal cell carcinoma. Our aim was to obtain long-term clinical follow-up data, clinicopathological and molecular characteristics, and incidence of LOT. Tissue microarrays were constructed from 574 tumors historically diagnosed as oncocytoma and surgically treated at Mayo Clinic between 1970 and 2012, and immunostained for CK7 and CD117. An extended immunophenotype was obtained on whole slide sections, along with FISH for CCND1 rearrangement status and chromosomal microarray for copy number status. In addition, two cases were retrospectively identified in a set of tuberous sclerosis complex (TSC)-associated neoplasms and three more cases diagnosed on needle core biopsies were obtained during routine clinical practice. Twenty-four cases of LOT were identified among 574 consecutive tumors diagnosed as oncocytoma and treated with partial or radical nephrectomy, corresponding to an incidence of 4.18% of tumors historically diagnosed as oncocytomas, and 0.35% of 6944 nephrectomies performed between 1970 and 2012. Overall, 29 cases of LOT were identified in three clinical settings: sporadic, TSC-associated, and end-stage renal disease (ESRD). Multifocality was seen only in the setting of TSC and ESRD. No metastases attributable to LOT were identified (median follow-up 9.6 years). There were no recurrent arm level copy number changes detected by chromosomal microarray and all tested cases were negative for CCND1 rearrangement by FISH. LOT is an uncommon eosinophilic renal neoplasm with an indolent prognosis that constitutes ∼4% of tumors historically diagnosed as oncocytoma. The morphologic, immunophenotypic, and molecular features of this neoplasm suggest it is a distinct entity of renal neoplasia., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To examine the clinicopathologic and immunohistochemical features of a group of newly defined low-grade oncocytic renal tumors (LOT) that have the "CD117 negative/cytokeratin (CK)7 positive" immunoprofile. We have queried our hospital database and found 4456 consecutive renal tumors between 2016 and 2019. Among these renal tumors, eight (8) cases meet the morphologic and immunohistochemical characterization for low-grade oncocytic renal tumor (LOT). The eight (8) patients' mean age is 56.6 years (range 39-70 years old), and the male to female ratio is 1:1. Macroscopically, these LOTs generally present with tan-brown and solid cut surfaces and demonstrate similar solid, compact nested growth pattern microscopically. Tumor cells exhibit oncocytic cytoplasm and uniformly rounded to oval nuclei. There are areas of edematous stroma containing dispersed single or small clustered tumor cells. All tumors are negative for CD117 and positive for CK7. Uniform reactivity is also found for BerEP4, cyclin D1, and SDHB. Besides, CD10, vimentin, and AMACR are either negative or only focally positive. All of the tumors are negative for CA9 and TFE. The Ki-67 index is less than 5% in the seven (7) internal cases. Seven (7) of the eight (8) patients who are available for follow-up are alive and without disease recurrence (mean follow-up period of 21.6 months, ranging from 6 to 43 months). We described a group of low-grade oncocytic renal tumors identified retrospectively in a large tertiary cancer center, which was probably the first report originated from China or even Asia in the English literature so far. These tumors demonstrated eosinophilic cytoplasm and low-grade appearing nuclei with a "CD117 negative/CK7 positive" immunoprofile. The incidence rate was about 3.7% of the oncocytic renal tumors and 0.18% of all the renal tumors that were received in our lab during the four-year period. It is necessary to separate this group of tumors by its characteristic morphologic and immunophenotypic features.

The histologic features of renal oncocytoma (RO) are similar to those for the more aggressive chromophobe renal cell carcinoma (ChRCC). To assess immunohistochemical markers of the two, the sensitivity and specificity of cytokeratin 7 (CK7) and C-kit, as well as hepatocyte nuclear factor-1β (HNF-1β), were analyzed. Typical cases of ChRCC and RO at Severance Hospital between July 2014 and July 2018 were selected retrospectively. Among 44 cases, 17 were unanimously compatible with ChRCC, 16 were RO, and 11 cases were indeterminate. Samples from all selected cases were used for immunostaining with antibodies against CK7, C-kit, HNF-1β, and CD10. Immunostaining demonstrated complete loss of HNF-1β expression in 11 out of 17 (64.7%) ChRCC cases and a partial, but significant loss in > 50% of tumor cells in the remaining 6 cases (35.3%). In contrast, HNF-1β expression was preserved in tumor cells of RO cases. Fourteen of 17 ChRCC cases (82.4%) were diffusely positive for CK7, whereas cases of RO were focal positive or negative. C-kit staining did not show a significant difference between ChRCC and RO. Two of five ChRCC cases showing diffuse immunoreactivity for CD10 had poor prognoses of local invasion, distant metastasis, or death. Loss of HNF-1β expression is a useful marker with which to diagnose ChRCC, especially in cases with confusing histologic findings or equivocal CK7 staining. Additionally, CD10 staining in high-grade ChRCC aids in diagnosis and prediction of the clinical prognosis.

Oncocytic mucoepidermoid carcinoma (OMEC) is a rare but diagnostically challenging variant of mucoepidermoid carcinoma (MEC). OMEC is notable for differential diagnostic considerations that are raised as a result of overlap with other benign and low-grade oncocytic salivary gland tumors. Diffuse and strong immunoreactivity of p63 protein may be useful in distinguishing OMEC from its mimics. However, focal p63 staining can be present in benign oncytomas. Presence of mucin-containing cells, mucinous cystic formation, and foci of extravasated mucin are considered a hallmark of MEC. True mucocytes may be, however, very few and hardly discernable in OMECs. Recent evidence has shown that most MECs harbor gene fusions involving MAML2. A retrospective review of archived pathology files and the authors' own files was conducted to search for "low-grade/uncertain oncocytic tumor," "oncocytoma," and "oncocytic carcinoma" in the period from 1996 to 2019. The tumors with IHC positivity for p63 and/or p40, and S100 negativity, irrespective of mucicarmine staining, were tested by next-generation sequencing using fusion-detecting panels to detect MAML2 gene rearrangements. Two index cases from consultation practice (A.S. and A.A.) of purely oncocytic low-grade neoplasms without discernible mucinous cells showed a CRTC1-MAML2 fusion using next-generation sequencing, and were reclassified as OMEC. In total, 22 cases of oncocytic tumors, retrieved from the authors' files, and from the Salivary Gland Tumor Registry, harbored the MAML2 gene rearrangements. Presence of mucocytes, the patterns of p63 and SOX10 immunopositivity, and mucicarmine staining were inconsistent findings. Distinguishing OMEC devoid of true mucinous cells from oncocytoma can be very challenging, but it is critical for proper clinical management. Diffuse and strong positivity for p63 and visualization of hidden mucocytes by mucicarmine staining may be misleading and does not always suffice for correct diagnosis. Our experience suggests that ancillary studies for the detection of MAML2 rearrangement may provide useful evidence in difficult cases.

Morphology, clinical behavior, and genomic profiles of renal oncocytoma (RO) and its malignant counterpart chromophobe renal cell carcinoma (ChRCC) are distinctly different. However, there is a substantial group of sporadic oncocytic tumors with peculiar hybrid phenotypes as well as a perplexing degree of morphologic and immunohistochemical overlap between classic RO and ChRCC with eosinophilic cytoplasm. The aim of this study is to provide detailed characterization of these hybrid tumors.Thirty-eight sporadic oncocytic neoplasms with ambiguous morphology from two institutions were reviewed by 4 pathologists. CKIT positivity was used as a selection criterion. We correlated CK7 and S100A1 immunostaining and detailed morphologic features with cytogenetic profiles. DNA from the formalin-fixed paraffin-embedded tissues was extracted and analyzed using cytogenomic microarray analysis (CMA) to evaluate copy number alterations (CNA) and ploidy. CMA categorized cases into 3 groups: RO (N = 21), RO variant (N = 7), and ChRCC (N = 10). Cytogenetic RO had either no CNA (48%) or loss of chromosome 1p, X, or Y (52%). RO variant had additional chromosomal losses [-9q, -14 (n = 2), -13] and chromosomal gains [+1q (n = 2), +4, +7 (n = 2), +13, +19, +20, and +22]. ChRCCs were either hypodiploid with numerous monosomies (40%) or hypotetraploid with multiple relative losses (60%). RO, RO variant, and ChRCC groups differed significantly in tumor architecture (p < 0.01), stroma (p = 0.013), presence of nuclear wrinkling, perinuclear halos, and well-defined cell borders in >5% of cells (p < 0.01), focal cell clearing (p = 0.048) and CK7 expression (p < 0.02). Pathologic prediction of the cytogenetic subtype using only two categories (benign RO or malignant ChRCC) would overcall or undercall up to 40% of tumors that were ChRCC based on cytogenetics. This finding provides the rationale for an intermediate diagnostic category of the so-called hybrid tumors (hybrid oncocytic/chromophobe tumor [HOCT]). HOCT was a heterogeneous group enriched for cytogenetic RO variant. Other HOCTs have a profile of either RO or ChRCC. The genomic profile allows classification of oncocytic tumors with ambiguous morphology into RO, RO variant, and ChRCC. Several architectural and cytologic features combined with CK7 expression are significantly associated with cytogenetic RO, RO variant, or ChRCC tumors. Doubled hypodiploidy by whole-genome endoduplication is a common phenomenon in eosinophilic ChRCC., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To comprehensively investigate the role of the N 6 -methyladenosine (m 6 A) erasers ALKBH5 and FTO in clear cell renal cell carcinoma (ccRCC), other RCC subtypes, and oncocytoma with respect to prognostic value and biomarker potential., Patients and Methods: The collection of tissue samples was performed within the framework of the Biobank at the Centre for Integrated Oncology Cologne-Bonn. The gene expressions of alkylation repair homologue 5 (ALKBH5) and fat mass and obesity-associated protein (FTO) were determined using quantitative real-time polymerase chain reaction. ALKBH5 and FTO expressions were further investigated in ccRCC, papillary RCC, chromophobe RCC, sarcomatoid RCC, oncocytoma, and benign renal tissue using tissue microarrays., Results: ALKBH5 mRNA, as well as ALKBH5 and FTO protein expressions, was significantly downregulated in ccRCC compared to normal tissue and most of the other studied tumour entities. Decreased mRNA levels of ALKBH5 and FTO correlated with a shortened overall and cancer-specific survival following nephrectomy., Conclusions: Taken together, our present data indicate that the m 6 A-demethylases ALKBH5 and FTO are dysregulated in ccRCC and could be used as prognostic biomarkers., (© 2020 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.)

An effective three-step proteomics workflow is proposed to overcome the pitfalls caused by polymers present in optimum cutting temperature (OCT)-embedded tissue during its preparation for mass spectrometry analysis. First, the OCT-embedded tissue biopsies are cleaned using ethanol and water in a sequential series of ultrasonic washes in an ultrasound bath (35 kHz ultrasonic frequency, 100% ultrasonic amplitude, 2 min of ultrasonic duty time). Second, a fast ultrasonic-assisted extraction of proteins is done using an ultrasonic probe (30 kHz ultrasonic frequency, 50% ultrasonic amplitude, 2 min of ultrasonic duty time, 1 mm diameter tip). Third, a rapid ultrasonic digestion of complex proteomes is performed using a microplate horn assembly device (20 kHz ultrasonic frequency, 25% ultrasonic amplitude, 4 min of ultrasonic duty time). As a proof of concept, the new workflow was applied to human normal and tumor kidney biopsies including chromophobe renal cell carcinomas (chRCCs) and renal oncocytomas (ROs). A successful cluster of proteomics profiles was obtained comprising 511 and 172 unique proteins found in chRCC and RO samples, respectively. The new method provides high sample throughput and comprehensive protein recovery from OCT samples.

Aim: The aim of this study was to investigate ELABELA (ELA) expression in benign and malignant renal tissues and expression differences in different nuclear grades of clear cell carcinomas., Materials and Methods: Patients that underwent surgery due to renal masses between the years of 2007 and 2017 were used. Control renal tissues (n = 23), papillary RCC (n = 23), clear cell RCC (CcRCC) [Fuhrman Grade1 (n = 23), Fuhrman Grade2 (n = 23), Fuhrman Grade3 (n = 23), Fuhrman Grade4 (n = 23)], and chromophobe RCC (n = 23) were included to the study. The Independent samples t-test was used for 2-point intergroup assessments and the one-way analysis of variance and posthoctukey test was used for the others. Values of P < 0.05 were considered statistically significant., Results: ELA immunoreactivity was observed in proximal and distal tubules in the kidney, but not in glomeruli in control tissues. When compared with control kidney tissue, a statistically significant increase was observed in ELA immunoreactivity in renal oncocytoma. In the chromophobe RCC, ELA immunoreactivity was significantly lower than control kidney tissue, whereas papillary RCC did not show ELA immunoreactivity. However, compared with control kidney tissue, ELA immunoreactivity was not observed in Fuhrman Grade 1 and Grade 2 CcRCC. Also, there was a significant decrease at Fuhrman Grade 3 and Grade 4 CcRCC compared with control kidney tissues. In the statistical analysis of ELA immunoreactivity among the Fuhrman nuclear grades of CcRCCs, The ELA immunoreactivity was higher at Grade 4 CcRCC than Grade 1, Grade 2, and Grade 3., Conclusion: ELA is a usefull molecule to differentiate benign and malign renal tumors. But further broad and comprehensive studies are needed to investigate cellular and molecular mechanisms of ELAs on malign transformation., Competing Interests: None

Context: A subset of thyroid carcinomas expresses an oncogenic paired box 8 (PAX8) and peroxisome proliferator activated receptor γ (PPARγ) fusion protein (PPFP). The PPARγ/PPFP ligand pioglitazone is highly therapeutic in a transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is therapeutic in patients with PPFP thyroid carcinoma is unknown., Case Description: Tumor blocks from 40 patients with progressive thyroid cancer despite standard-of-care therapy were screened for PPFP, and the tumor from only one patient (2.5%) was positive. The patient had a 6.0-cm acetabular soft tissue metastasis from Hürthle cell carcinoma that caused severe pain on weight bearing and had a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastatic lesion was 3.9 cm, the thyroglobulin level was 49.4 ng/mL, and the patient was pain-free. Thirteen months after discontinuation of pioglitazone, the metastatic lesion was 3.6 cm, the thyroglobulin level was 4.7 ng/mL, and the patient remained pain-free., Conclusions: Pioglitazone may be therapeutic in patients with PPFP thyroid cancer. However, thyroid cancers that are progressive despite standard-of-care therapy appear to only rarely express PPFP.

Renal oncocytoma and chromophobe renal cell carcinoma have been long recognized as distinct tumors; however, it remains unknown if uniform diagnostic criteria are used to distinguish these tumor types in practice. A survey was distributed to urologic pathologists regarding oncocytic tumors. Responses were received from 17 of 26 invitees. Histologically, more than 1 mitotic figure was regarded as most worrisome (n=10) or incompatible (n=6) with oncocytoma diagnosis. Interpretation of focal nuclear wrinkling, focal perinuclear clearing, and multinucleation depended on extent and did not necessarily exclude oncocytoma if minor. Staining techniques most commonly used included the following: cytokeratin 7 (94%), KIT (71%), vimentin (65%), colloidal iron (59%), CD10 (53%), and AMACR (41%). Rare cytokeratin 7-positive cells (≤5%) were regarded as most supportive of oncocytoma, although an extent excluding oncocytoma was not universal. Multiple chromosomal losses were most strongly supportive for chromophobe renal cell carcinoma diagnosis (65%). Less certainty was reported for chromosomal gain or a single loss. For tumors with mixed or inconclusive features, many participants use an intermediate diagnostic category (82%) that does not label the tumor as unequivocally benign or malignant, typically "oncocytic neoplasm" or "tumor" with comment. The term "hybrid tumor" was used variably in several scenarios. A slight majority (65%) report outright diagnosis of oncocytoma in needle biopsies. The morphologic, immunohistochemical, and genetic characteristics that define oncocytic renal tumors remain incompletely understood. Further studies correlating genetics, behavior, and histology are needed to define which tumors truly warrant classification as carcinomas for patient counseling and follow-up strategies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Adenohypophysis spindle cell oncocytoma (ASCO) is a rare tumor recently reported by Roncaroli et al in 2002. This tumor is considered a grade I tumor by the World Health Organization.We report a rare case of malignant ASCO with repeating recurrences and a high Ki-67 index-a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological tests.We represent a 30-year-old man who had suffered from headaches, diplopia, and impaired visual field and acuity. His magnetic resonance imaging revealed an abnormal sellar mass and was originally misdiagnosed as a pituitary macroadenoma. We present detailed analysis of the patient's disease course and review relevant literature.When surgically treated, the specimen revealed a typical histopathology pattern of ASCO. The tumor recurred for several times and the patient underwent 3 surgeries and 1 γ-knife treatment, which was accompanied by a continuously increasing Ki-67 index.This is the first reported case of malignant ASCO (WHO III-IV grade). Despite its rarity, ASCO should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Stage is an important prognostic factor in renal tumours and dissemination to regional lymph nodes is associated with poor outcomes. Lymph nodes are routinely assessed by immunohistochemistry and microscopic evaluation, a time-consuming process where micrometastases might go undiagnosed. We evaluate an alternative method for detecting metastatic cells in sentinel nodes (SNs) by flow cytometry., Methods: A total of 15 nodes from 5 patients diagnosed with renal tumours were analysed by flow cytometry. Staining for the intracellular marker cytokeratin 18 (CK18) with the surface markers carbonic anhydrase IX (CA9) and Cadherin 6 were used in flow cytometry analysis. Peripheral blood mononuclear cells (PBMCs) with the addition of known concentrations of cancer cell lines were analysed to investigate the sensitivity of micrometastasis detection., Results: Stability of the assay was marked by low intra-assay variability (coefficient of variance ⩽16%) and low inter-assay variability (R 2 =0.9996-1). Eight nodes in four patients were positive for metastasis; six of them were considered being micrometastatic. These metastases were undetected by routine pathology and the patients were restaged from pN0 to pN1., Conclusions: Flow cytometry is able to detect micrometastases in lymph nodes of renal tumour patients that were undetected under H&E examination.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Spindle cell oncocytoma (SCO) is an extremely rare neoplasm of the sellar region recognized as a distinct benign histopathological subtype of pituitary tumors in the 2007 World Health Organization classification of tumors of the central nervous system. The morphology of its neoplastic cells (spindle cells and granular eosinophilic cytoplasm) is common to several other lesions so that immunohistochemistry, together with ultrastructural examination, becomes essential in solving this differential diagnosis. Despite being labeled as benign, recurrence is described. Herein, we report a case of SCO in a 77-year-old man and discuss the diagnostic difficulties, ultrastructural aspects, and prognostic factors.

Chordoid glioma of the third ventricle is a rare neuroepithelial tumor characterized by a unique histomorphology and exclusive association with the suprasellar/third ventricular compartment. Variously interpreted as either astrocytic- or ependymal-like, and speculatively ascribed to the lamina terminalis/subcommissural organ, its histogenesis remains, nevertheless, unsettled. Here, we report on a suprasellar chordoid glioma occurring in a 52-year-old man. Although displaying otherwise typical morphological features, the tumor was notable for expression of thyroid transcription factor 1, a marker of tumors of pituicytic origin in the context of the sellar region. We furthermore found overlapping immunoprofiles of this example of chordoid glioma and pituicytic tumors (pituicytoma and spindle cell oncocytoma), respectively. Specifically, phosphorylated ribosomal protein S6, a marker of mTOR pathway activation, was expressed in both groups. Based on these findings, we suggest that chordoid glioma and pituicytic tumors may form part of a spectrum of lineage-related neoplasms of the basal forebrain., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hurthle cells are not uncommonly encountered in thyroid fine needle aspiration cytology (FNAC) smears. They are easily recognized by their distinct cytomorphology in cytological preparations, i.e. large, polygonal cells displaying uniform, rounded nuclei, often prominent nucleoli and abundant granular cytoplasm. Hurthle cells can be seen in both non-neoplastic and neoplastic thyroid lesions which can pose diagnostic dilemma to cytopathologists, especially when the lesions are focally sampled. We describe a case of solitary thyroid nodule in a 46-year-old male, whose aspirates comprised predominantly of Hurthle cells exhibiting nuclear features suspicious of papillary carcinoma, which turned out to be Hurthle cell carcinoma on subsequent histological sections. The potential diagnostic pitfalls of Hurthle cell lesions and associated conditions in thyroid FNA are discussed. The presence of Hurthle cell change in a wide variety of thyroid lesions can be diagnostically challenging. However, accurate diagnosis can still be made with careful observation of the predominant cell population, nuclear features and whether there is abundant colloid or lymphocytes in the background.

Objectives: We evaluated SOX10 (SRY-related HMG-box 10) in differentiating acinic cell carcinoma (AciCC) from other salivary gland neoplasms with oncocytic features on fine-needle aspiration cell blocks (FNA CB) and compared its performance to DOG1 (discovered on gastrointestinal stromal tumor 1)., Material and Methods: 35 FNA CB of oncocytic salivary gland neoplasms, i.e. 13 cases of AciCC, 16 of Warthin tumor (WT), 3 of mucoepidermoid carcinoma (MEC) and 3 of oncocytoma (ONC), and 75 salivary gland resections, i.e. 26 AciCC, 7 WT, 36 MEC, 3 ONC, 2 mammary analog secretory carcinomas (MASC) and 1 papillary cystadenoma were stained for SOX10 and DOG1., Results: None of the benign oncocytic neoplasms were immunoreactive for SOX10 on CB or resection, similar to DOG1. On CB, 61.5 and 77% of AciCC were positive for SOX10 and DOG1, respectively. All surgically resected AciCC cases were positive for SOX10 and DOG1; other malignant oncocytic lesions such as MEC and MASC demonstrated variable SOX10 and DOG1 staining., Conclusion: The use of SOX10 may increase the diagnostic accuracy of oncocytic lesions on FNA. In this context, SOX10 is equivalent to DOG1 in ruling out benign lesions such as WT and ONC; however, negative results for SOX10 as well as DOG1 do not favor a benign diagnosis since MEC is often negative for both markers., (© 2015 S. Karger AG, Basel.)

Pituicytomas are neoplasms that arise from pituicytes, which are specialized glia of the posterior pituitary. Pituicytes have 5 ultrastructural variants: light, dark, granular, ependymal, and oncocytic. Granular cell tumors of the pituitary gland are thought to arise from granular pituicytes. Spindle cell oncocytomas are considered to arise from folliculostellate cells, which are sustentacular cells of the adenohypophysis. Recent data suggest that, whereas pituicytes and all 3 tumor types are positive for TTF-1, folliculostellate cells are negative for TTF-1. We investigated 7 spindle cell oncocytomas, 4 pituicytomas, and 3 granular cell tumors for their genetic (BRAF(V600E) mutation and BRAF-KIAA fusion), immunohistochemical (GFAP, vimentin, S100 protein, olig2, IDH1-R132H, NF, galectin-3, chromogranin-A, CD56, EMA, CAM5.2, CD68, TTF-1, and bcl-2), and ultrastructural features to refine their classification. All tumors had nuclear positivity for TTF-1 and were negative for CAM5.2, chromogranin-A, and NF. GFAP, vimentin, S100, galectin-3, EMA, and CD68 were variably positive in the majority of the 3 tumor groups. Olig2 was only positive in 1 pituicytoma. Whereas granular cell tumors were negative for bcl-2 and CD56, pituicytomas and spindle cell oncocytomas showed variable positivity. All tumors were negative with the IDH1-R132H mutation-specific antibody, and none had evidence of BRAF alterations (BRAF(V600E) mutation and BRAF-KIAA fusion). Diffuse TTF-1 expression in nontumorous pituicytes, pituicytomas, spindle cell oncocytomas, and granular cell tumors indicates a common pituicyte lineage. The ultrastructural variants of pituicytes are reflected in these 3 morphologic variants of tumors arising from these cells. We propose the terminology "oncocytic pituicytomas" and "granular cell pituicytomas" to refine the classification of these lesions.

Papillary renal cell carcinoma (PRCC) is traditionally classified into type 1 and type 2. Recently, an oncocytic variant of PRCC has been described. We report a series of 6 oncocytic renal papillary tumors (OPRCC) which tended to occur in older patients (mean, 56.8 years) with a male preference (male-to-female ratio is 5:1). All 6 patients are alive with no evidence of disease after initial resection, showing an indolent clinical behavior. Histologically, tumors exhibited predominant papillary structure with delicate fibrovascular cores. Papillae were lined by single layers of cells with large, deeply eosinophilic and finely granular cytoplasms and round regular nucleus. The phagocytosis of tumor cells was frequently and evidently seen in our cases that hemosiderin-laden tumor cells and foamy tumor cells were noticed in five and four cases respectively. All tumors were immunoreactive for racemase, vimentin, CD10, and MET and negative for CD117. While E-cadherin, EMA, and cytokeratin 7 exhibited variable immunopositivity. FISH analysis was performed in five of six cases and found heterogeneous results. Trisomy of chromosomes 7 was found in three cases and trisomy of chromosomes 17 in two cases. Loss of chromosome Y was noted in one of four tumors in male patients. MET gene status was also investigated by direct sequencing in all 6 cases and found no distinct mutation in any case. These results suggest that OPRCC shows distinct morphology, indolent clinical behavior, and similar immunohistochemical and cytogenetic features with PRCC, seems to be a variant in the PRCC group. Whether the strong expression of MET indicates a potential therapeutic target is still unknown and requires further investigation in clinical trials.

Aims: PAX8 is a cell lineage-specific transcription factor which plays a crucial role in the organogenesis of the kidney, thyroid gland and Müllerian duct. A previous study showed that PAX8 is a specific and sensitive marker for both renal and ovarian carcinomas. The purpose of this study is to investigate PAX8 expression using a new monoclonal PAX8 antibody in a larger number of renal epithelial neoplasms including clear cell renal cell carcinoma, papillary renal cell carcinoma, chromophobe renal cell carcinoma and renal oncocytoma., Methods: PAX8 immunohistochemical staining was performed on tissue microarrays containing 84 cases of clear cell renal cell carcinoma, 66 cases of chromophobe renal cell carcinoma, 57 cases of papillary renal cell carcinoma and 16 cases of renal oncocytoma., Results: PAX8 expression was detected in 93% (78/84) of cases of clear cell renal cell carcinoma, 80% (53/66) of cases of chromophobe renal cell carcinoma, 95% (54/57) of cases of papillary renal cell carcinoma and 94% (15/16) of cases of renal oncocytoma., Conclusions: PAX8 is expressed in the majority of renal epithelial neoplasms including renal cell carcinomas and oncocytomas and the monoclonal PAX8 antibody is more sensitive than polyclonal antibody to detect chromophobe renal cell carcinoma. These results showed that PAX8 is a valuable marker for nephric neoplasms.

Aims: To develop an immunohistochemical strategy for distinguishing renal oncocytoma (RO) from the eosinophilic variant of chromophobe (ChRCC), and papillary (PRCC) and clear cell (CRCC) renal cell carcinoma containing eosinophilic cytoplasm in core biopsy specimens., Methods and Results: Cluster analysis was performed on immunohistochemical data from 21 RO, 16 ChRCC, 16 CRCC and 20 PRCC patients. A panel of CK7, C-kit, S100A1 and vimentin clustered into four groups. Cluster A (94% ChRCC) expressed C-kit and CK7 and lacked S100A1 and vimentin. Cluster B (95% RO) expressed C-kit, S100A1, focal CK7 (single or small clusters of cells) and lacked vimentin. Cluster C comprised a mixture of PRCC and CRCC with no expression of C-kit or CK7 and variable S100A1 and vimentin. PRCC with strong expression of CK7 clustered into group D. A panel of S100A1 (positive) and focal CK7 expression distinguished RO from ChRCC with 91% sensitivity and 93% specificity. A panel of vimentin (negative) and C-kit (positive) distinguished RO from CRCC with 83% sensitivity and 86% specificity and RO from PRCC with 79% sensitivity and 88% specificity., Conclusions: Hierarchical cluster analysis is an effective approach to analyse high-volume immunohistochemical data to generate an optimal panel in the differential diagnosis of oncocytoma from its mimics., (© 2011 Blackwell Publishing Limited.)

Encapsulated papillary oncocytic neoplasms (EPONs) of the thyroid are rare tumors, whose relationship to other thyroid tumors has not been thoroughly elucidated. Earlier, they have been regarded as variants of papillary thyroid carcinoma (PTC), hyperplastic lesions, and follicular neoplasms. Eighteen EPONs were retrieved from our surgical pathology files and reviewed for defining morphologic features. Cases having the typical nuclear features of PTC were excluded. Immunohistochemistry (IHC) for CK19, HBME1, and CD56 was carried out. Microdissection, polymerase chain reaction, and sequencing of exon 15 of the BRAF gene were completed. Cases were evaluated for rearranged in transformation/papillary thyroid carcinoma RET/PTC rearrangement by fluorescent in situ hybridization (FISH). The majority of the tumors exhibited a distinctive histologic appearance. They were composed of true papillae lined by a single layer of predominantly cuboidal cells with oncocytic cytoplasm; hobnailing was typically prominent. Three tumors showed taller cells with uniformly apical nuclei and no hobnailing. Ten of 18 cases showed vascular and/or capsular invasion; hence, if the diagnostic criteria used to evaluate follicular neoplasms are applied, more than half of the tumors would be considered minimally invasive carcinomas. No cases were immunoreactive with antibodies to HBME1, whereas only 1 of 13 was immunoreactive for CK19. Six of 7 interpretable cases were immunoreactive for CD56. No BRAF point mutations or RET/PTC rearrangements were identified in the examined cases. All patients were alive at the time of last follow-up and no locally recurrent disease had been reported; however, 1 case was remarkable for a lymph node metastasis. Our results confirm that EPONs are histologically, immunohistochemically, and molecularly distinct from papillary thyroid carcinoma and seem to be most related to follicular neoplasms.

Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC., Methods: Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors., Results: A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities., Conclusions: Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

This study was undertaken to elucidate the genetic patterns of the renal cell neoplasms of oncocytosis and to compare them with those found in cases with multiple oncocytomas. Three cases of renal oncocytosis and 6 cases of multiple oncocytomas were analyzed. Fluorescence in situ hybridization analysis was performed with centromeric probes for chromosomes 1, 2, 6, 10, and 17 that are typically lost in chromophobe renal cell carcinoma but not in oncocytoma. Immunohistochemistry for cytokeratin 7, parvalbumin, and S100A1 was performed in all cases. Eleven tumors were present in the 3 kidneys with oncocytosis. One of these was a classic chromophobe renal cell carcinoma. In the other 10, none showed any chromosomal losses, whereas 3 showed gains of all 5 chromosomes and 1 had gains of chromosomes 2 and 10. The chromophobe renal cell carcinoma showed losses of chromosome 1, 6, 10, and 17. Twelve of 14 tumors from the patients with multiple oncocytomas showed no loss of any of the chromosomes 1, 2, 6, 10, or 17 and 2 had loss of chromosome 1. All the tumors from kidneys with renal oncocytosis showed strong parvalbumin immunoreactivity, whereas cytokeratin 7 and S100A1 expression were variable. In summary, the renal cell neoplasms of oncocytosis seem to have distinct morphologic, immunohistochemical, and cytogenetic profiles and likely are a distinct entity, not closely related to oncocytoma or chromophobe renal cell carcinoma.

Background: Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe-oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear., Objective: To determine the clinical course of hybrid RCC., Design, Setting, and Participants: Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells)., Interventions: Radical tumor nephrectomy or nephron-sparing surgery., Measurements: Recurrence-free and tumor-specific survival., Results and Limitations: Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n=17), pT2 in 23.5% of tumors (n=8), and pT3a in 26.5% of tumors (n=9). Low-grade RCC was found in 76.5% of tumors (n=26), and vascular invasion was found in 11.8% of tumors (n=4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively., Conclusions: Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses., (Copyright © 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To study the expression of a novel marker, Wnt-5a, in renal epithelial neoplasms and determine its clinicopathological significance., Methods: Immunohistochemical analysis of Wnt-5a was carried out in normal human kidney samples as well as in 123 primary renal epithelial neoplasms including 37 clear cell renal cell carcinomas (RCCs), 24 papillary RCCs (15 type 1 and 9 type 2), 25 chromophobe RCCs, 11 Xp11 translocation carcinomas, 6 mucinous tubular and spindle cell carcinomas, and 20 oncocytomas., Results: Wnt-5a was expressed in 18.9% (7/37) of clear cell RCCs, 12.5% (3/24) of papillary RCCs, 16% (4/25) of chromophobe RCCs, 18.2% (2/11) of Xp11 translocation carcinomas, 0% (0/6) of mucinous tubular and spindle cell carcinomas, and 100% (20/20) of oncocytomas. There was a significant difference in Wnt-5a immunohistochemistry between renal oncocytoma and the other subtypes of RCC (P < 0.01)., Conclusions: Our results indicate that Wnt-5a is a potentially useful immunohistochemical marker for the complex differential diagnosis between oncocytoma and other subtypes of RCC and also suggest that Wnt-5a may be a tumor suppressor gene in RCC.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

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

The differential diagnosis between benign salivary oncocytoma (ONC) and low-grade malignant acinic cell carcinoma (ACC) can be difficult due to a significant histomorphological overlap of the structural and cytological presentation of both tumor types. To the best of our knowledge a comprehensive study comparing (immuno-)histological markers in cases of difficult differential diagnosis between ONC and ACC has not yet been performed. We investigated a panel of different immunohistochemical (CK5/6, CK14, CK7, CK18, p63 and Ki67) and histochemical (PAS, alpha-amylase) markers in 12 cases of ONC and 19 cases of ACC. The statistically significant stronger expression of CK7 in ONC and stronger expression of PAS and alpha-amylase in ACC in routine practice each is hampered by a pronounced overlap between both tumor groups. The obligate presence of an additional small basal cell component in all cases of ONC, demonstrable with p63 and CK5/6, enables a straightforward distinction from ACC, being constantly devoid of a basal cell component. Unexpectedly, CK14 is not a suitable marker for a reliable proof of these basal cells. The detection of this basal cell component in ONC in routine Hematoxylin-eosin stain is difficult and in some cases not possible; therefore, immunohistochemistry with p63 or CK5/6 is recommended for selected cases.

Adrenocortical oncocytoma is a rare epithelial tumor only described in adults. We report the case of a 12-year-old female who presented a left adrenal mass with abdominal pain, fatigue, acne vulgaris, and elevation of the androstenedione and total testosterone. She had an adrenalectomy. A diagnosis of adrenocortical oncocytoma was made after detailed histological, immunohistochemical, and ultrastructural studies., ((c) 2007 Wiley-Liss, Inc.)

We attempted to investigate the clinicopathological correlation of renal oncocytoma (RO) with renal vein extension. We identified seven ROs with extension into the branches of renal vein. The age of seven patients ranged from 61 to 82 years. Five cases were identified incidentally; two patients had gross hematuria. After surgery, all patients were alive and free of tumors with follow-up of 1 to 5 years (mean = 3.6). Oncocytomas measured from 2.2 to 7.5 cm. Renal vein extension was grossly suspected in five of seven cases and histologically confirmed in all seven cases. Tumor cells were positive for cytokeratins, mitochondrial-antigen (MIA), epithelial membrane antigen (EMA), and parvalbumin; five of seven tumors were focally positive for CD117. Ultrastructurally, the cytoplasm was packed by mitochondria. Molecular genetic analysis did not detect abnormal numbers of chromosomes 1, 2, 6, 7, 10, 17, and XY by fluorescence in situ hybridization, loss of heterozygosity on 3p and mutation of von Hippel-Lindau gene in all cases. Array comparative genomic hybridization analysis of two cases did not show any major genetic changes. Our conclusions are as follows: (1) renal oncocytomas may have intravascular extension to the branches of the renal vein; (2) renal oncocytomas with intravascular extension to the branches of the renal vein have the same morphological, immunohistochemical, and cytogenetic findings as have their counterparts without evidence of intravascular invasion; (3) the absence of metastases suggests an overall benign behavior of this tumor, but this has to be substantiated by further studies with a long-term follow-up; and (4) in a renal tumor with granular cytoplasm showing renal vein extension, it is necessary to carefully exclude renal cell carcinomas such as chromophobe RCC, oncocytic variant of papillary RCC, and granular variant of clear cell RCC.

Renal carcinomas harboring the TFE-3 translocation are rare and occur predominately in children and adolescents. Here, we report a case of infantile renal carcinoma with TFE3 translocation and show that the cell cycle is deregulated in this type of carcinoma. It is characterized by nuclear accumulation of cyclin D1 and D3 in combination with high levels of cyclin-dependent kinase inhibitor p21Cip1/Waf1 but without accumulation of p53, p16INK4a, or mdm2. The combined overexpression of p21, cyclin D1, and cyclin D3 was found exclusively in this type but not in other, more common types of renal carcinoma/oncocytoma (n=27). These results further underscore that renal carcinomas with Xp11. 2 translocations/TFE3-gene fusion represent a special type of renal neoplasm showing deregulation of specific cell cycle components. The analysis of further cases has to prove whether the derangement of the cell cycle is uniform and correlates with the specific type of molecular genetic derangement.

Context: The separation of chromophobe renal cell carcinoma, oncocytoma, and clear cell renal cell carcinoma using light microscopy remains problematic in some cases., Objective: To determine a practical immunohistochemical panel for the differential diagnosis of chromophobe carcinoma., Design: Vimentin, glutathione S-transferase alpha (GST-alpha), CD10, CD117, cytokeratin (CK) 7, and epithelial cell adhesion molecule (EpCAM) were investigated in 22 cases of chromophobe carcinoma, 17 cases of oncocytoma, and 45 cases of clear cell carcinoma., Results: Vimentin and GST-alpha expression were exclusively observed in clear cell carcinoma. CD10 staining was more frequently detected in clear cell carcinoma (91%) than in chromophobe carcinoma (45%) and oncocytoma (29%). CD117 was strongly expressed in chromophobe carcinoma (82%) and oncocytoma (100%), whereas none of the cases of clear cell carcinomas were immunoreactive. Cytokeratin 7 was positive in 18 (86%) of 22 cases of chromophobe carcinoma, whereas all oncocytomas were negative for CK7. EpCAM protein was expressed in all 22 cases of chromophobe carcinoma in more than 90% of cells, whereas all EpCAM-positive oncocytomas (5/17; 29%) displayed positivity in single cells or small cell clusters., Conclusions: Using the combination of 3 markers (vimentin, GST-alpha, and EpCAM), we achieved 100% sensitivity and 100% specificity for the differential diagnosis of chromophobe carcinoma, oncocytoma, and clear cell carcinoma. The pattern of "vimentin(-)/GST-alpha(-)" effectively excluded clear cell carcinoma, and homogeneous EpCAM expression confirmed the diagnosis of chromophobe carcinoma rather than oncocytoma. CD117 and CK7 were also useful markers and could be used as second-line markers for the differential diagnosis, with high specificity (100%) and high sensitivity (90% and 86%, respectively).

Oculocutaneous oncocytic tumors (OCOTs) are uncommon neoplasms that have been reported only rarely in the dermatopathology literature and whose immunophenotypic profile has not been well characterized. The clinical, histologic, and immunophenotypic features of 2 cases seen by the authors were assessed, and relevant publications in the literature were reviewed. Both patients with OCOTs were adult women with gradually enlarging, asymptomatic lesions involving the caruncle; they were locally excised. Histologically, the tumors were well-circumscribed nodules comprised of large oxyphilic cells arranged in confluent sheets and forming glandular spaces with secretory material. Microcystic areas and sparse intermingled goblet-cells were also apparent. Nuclear atypia and infiltrative growth were absent. Mitotic activity was absent in one case; a single mitotic figure was identified in the other. Immunostains demonstrated uniform expression of pankeratin and mitochondrial antigens. Both neoplasms were also labeled for markers associated with cutaneous adnexal, lacrimal, and minor salivary glandular tissue, including alpha-1-antitrypsin, gross cystic disease fluid protein-15, carcinoembryonic antigen, lysozyme and MUC1; each case expressed 4 of the 5 substances. Some cells expressed cytokeratins 5/6 and p63 consistent with the presence of basal-type differentiation in a subset of cells. No definite evidence of myoepithelial differentiation was demonstrated, as stains for smooth muscle actin, muscle-specific actin, and S100 protein were negative. Estrogen and progesterone receptor proteins were absent; strong cytoplasmic immunoreactivity for androgen receptor protein was evident, but nuclear staining was absent. The authors conclude that OCOTs show glandular differentiation. A review of the literature disclosed that none of these lesions arising in the caruncle behaved aggressively, in contrast to occasional tumors in other oculocutaneous sites.

Immunohistochemical staining for cytokeratin 7 (CK7), KIT, and PAX2 expression was performed on 91 renal neoplasms, 37 conventional (clear cell) renal cell carcinomas (CRCCs), 20 papillary RCCs (PRCCs), 11 chromophobe RCCs (ChCs), and 23 oncocytomas, with available karyotypes. All ChCs, 19 PRCCs, 2 CRCCs, and 1 oncocytoma were CK7+; all ChCs, 22 oncocytomas, 2 CRCCs, and no PRCCs expressed KIT; PAX2 was positive in 31 CRCCs, 17 PRCCs, 20 oncocytomas, and 1 ChC. The predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37); PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7-/KIT+/PAX2+ (19/23). Cytogenetic analysis showed that the sole PAX2+ ChC had a retained chromosome 10, and all ChCs with chromosome 10 loss were PAX2-. These results identify specific staining patterns of the 4 major histologic subtypes of renal neoplasms and raise the question of a relationship between chromosome 10 loss and loss of PAX2 expression in ChC.

A 72-year-old man presented with a 2-year history of epiphora. CT revealed an extensive inferomedial orbital tumor connected to the lacrimal sac and duct. Incisional biopsy revealed malignant oncocytoma of the lacrimal sac. The patient was treated with exenteration and maxillectomy followed by a course of postoperative radiotherapy. Patients with malignant oncocytoma may present with simple epiphora in absence of other signs and symptoms such as blood stained tearing or purulent rhinorrhea.

Introduction: Cancer of thyroid gland is the most common malignancy of the endocrine system. The treatment improvement could be achieved by early diagnosis. The aim of the study was to identify cancer specific antigenes with use of peptide libraries., Material and Methods: The material from 6 patients with thyroid cancer (4 with papillary cancer, 1 with follicular cancer and 1 with oxyphilic tumor) were analyzed. It was performed with use of lipophylic peptide libraries by direct comparison of staining of specimens prepared from normal and malignant tissue., Results: Preliminary results confirm practical value of peptide libraries in early diagnostics of thyroid cancer., Conclusions: It is important to optimize construction of peptide libraries by using different staining agents hydrolyzed by proteases.

Background: Lesions of the thyroid gland composed of Hurthle cells encompass pathologic entities ranging from hyperplastic nodules with Hurthle cell metaplasia to Hurthle cell carcinomas. The cytologic distinction between these entities can be diagnostically challenging. Many cytologic features of Hurthle cell lesions that distinguish neoplastic Hurthle cell lesions requiring surgery from those that are benign and nonneoplastic have been described, but with variable usefulness. This is due, in part, to the small numbers of cases examined in previous studies and the limited application of statistical analysis. A morphologic study was made of 139 Hurthle cell lesions of the thyroid gland and statistical analysis applied to identify a set of cytomorphologic features that distinguish benign Hurthle cell lesions (BHCL) from Hurthle cell neoplasms (HCN)., Methods: Fine-needle aspiration biopsies (FNABs) of thyroid nodules with a predominant Hurthle cell component and corresponding histologic followup were included in the study. Cases were divided into BHCL and HCN groups on the basis of the histologic diagnosis. All cases were reviewed to assess the following 14 cytologic features: overall cellularity, cytoarchitecture, percentage of Hurthle cells, percentage of single cells, percentage of follicular cells observed as naked Hurthle cell nuclei, background colloid, chronic inflammation, cystic change, transgressing blood vessels (TBV), intracytoplasmic lumina, presence of multinucleated Hurthle cells, nuclear to cytoplasmic ratio, nuclear pleomorphism/atypia, and nucleolar prominence. The results were evaluated by using univariate and stepwise logistic regression (SLR) analysis; statistical significance was achieved at P-values < 0.05., Results: One hundred thirty-nine FNAB specimens, corresponding to 56 HCN and 83 BHCL, fulfilled the study criteria. Six of the 14 cytologic features evaluated were shown by univariate analysis to be statistically significant in predicting HCN: nonmacrofollicular architecture (P < 0.001), absence of background colloid (P < 0.001), absence of chronic inflammation (P < 0.001), presence of TBV (P < 0.001), > 90% Hurthle cells (P < 0.001), and >10% single Hurthle cells (P = 0.014). The first four of these features were also shown to be statistically significant in the SLR analysis (P = 0.005, 0.010, 0.016, and 0.045, respectively), and when all four of these features were present HCN was correctly identified 86% of the time., Conclusions: In the current study of 139 FNAB specimens of thyroid Hurthle cell nodules, 14 cytologic features were examined and 6 were found to be statistically significant in identifying HCN. The following four features, when found in combination, were found to be highly predictive of HCN: nonmacrofollicular architecture, absence of colloid, absence of inflammation, and presence of TBV., (Copyright 2006 American Cancer Society.)

Aim: This study was aimed to determine p73 status in thyroid tumours., Methods: Differential expression of the TAp73, DeltaTAp73 transcripts was measured in a panel of 60 thyroid malignancies by quantitative RT-PCR., Results: By comparison to normal thyroid tissue surrounding the tumours, we observed significant downregulation of TP73 transcripts in adenomas and in differentiated carcinomas. Correlations were found in normal tissue specimens between the expression of TAp73 and DeltaNp73 transcripts and that of p53, p14ARF p16INK4a, but these correlations were lost in carcinomas (PTC or FTC)., Conclusions: We have found significant variations of TAp73, DeltaNp73, p53, p14ARF p16INK4a, expressions and correlations between the expressions of those different genes in thyroid cancer.

Chromophobe renal cell carcinoma (ChRCC) and oncocytoma might mimic each other histologically. We studied the immunohistochemical staining pattern of caveolin-1 in 21 ChRCCs and 26 oncocytomas and compared it with cytokeratin (CK) 7 to evaluate its usefulness in differentiating these 2 neoplasms. All 21 ChRCCs (100%) were positive for caveolin-1, 20 of which were stained in 20% or more of the tumor cells. In contrast, only 3 (12%) of 26 oncocytomas showed positivity in fewer than 20% tumor cells and 23 (88%) of 26 were negative. In the nonneoplastic kidney, positive caveolin-1 staining was detected in the interstitial blood vessels and the parietal cells of the Bowman capsules but not in the tubular epithelium and glomerular and peritubular capillaries. All 21 ChRCCs (100%) were positive for CK7, with 18 (86%) stained in 20% or more of the tumor cells and 3 (14%) in fewer than 20%. Of 26 oncocytomas, 25 (96%) were positive for CK7, with 7 (27%) stained in 20% or more of the tumor cells and 18 (69%) in fewer than 20%. These results strongly suggest that caveolin-1 immunohistochemical analysis is useful for differentiating ChRCC from oncocytoma and is superior to CK7.