Oncocytes Research Articles

Characterization of Intraductal Papillary Neoplasm of the Bile Duct with Respect to the Histopathologic Similarities to Pancreatic Intraductal Papillary Mucinous Neoplasm.

Intraductal papillary neoplasms of the bile duct (IPNBs) are known to show various pathologic features and biological behaviors. Recently, two categories of IPNBs have been proposed based on their histologic similarities to pancreatic intraductal papillary mucinous neoplasms (IPMNs): type 1 IPNBs, which share many features with IPMNs; and type 2 IPNBs, which are variably different from IPMNs. The four IPNB subtypes were re-evaluated with respect to these two categories. Intestinal IPNBs showing a predominantly villous growth may correspond to type 1, while those showing papillay-tubular or papillay-villous growth correspond to type 2. Regarding gastric IPNB, those with regular foveolar structures with varying numbers of pyloric glands may correspond to type 1, while those with papillary-foveolar structures with gastric immunophenotypes and complicated structures may correspond to type 2. Pancreatobiliary IPNBs that show fine ramifying branching may be categorized as type 1, while others containing many complicated structures may be categorized as type 2. Oncocytic type, which displays solid growth or irregular papillary structures, may correspond to type 2, while papillary configurations with pseudostratified oncocytic lining cells correspond to type 1. Generally, type 1 IPNBs of any subtype develop in the intrahepatic bile ducts, while type 2 IPNBs develop in the extrahepatic bile duct. These findings suggest that IPNBs arising in the intrahepatic ducts are biliary counterparts of IPMNs, while those arising in the extrahepatic ducts display differences from prototypical IPMNs. The recognition of these two categories of IPNBs with reference to IPMNs and their anatomical location along the biliary tree may deepen our understanding of IPNBs.

Ultrastructural characteristics of primary renal epithelial tumours with granular oncocytic cytoplasm

Background/Aim. Ultrastructural analysis of tumours has shown many common characteristics of certain neoplasms, as well as their specificities. Primary renal epithelial tumours with granular oncocytic cytoplasm is a very heterogeneous group in their histological origin and biological behaviour, which results in a difference in treatment and prognosis of the disease, making accurate morphological diagnosis necessary. The aim of this study was to determine ultrastructural similarities and differences among primary renal epithelial tumours with granular oncocytic cytoplasm. Methods. The analysis of archival and routine material in the archives of the Department of Pathology, University Hospital in Plzen, Czech Republic, as well as archival and routine material in the Centre for Pathology and Histology, Clinical Centre of Vojvodina in Novi Sad, discovered 346 primary renal epithelial tumours with granular oncocytic cytoplasm and divided them into 5 groups: 1) renal oncocytoma (RO) (234 tumours), 2) oncocytic papillary renal cell carcinoma (OPRCC) (12 tumours), 3. sporadic renal hybrid oncocytic/ chromophobe tumour (HOCT) without evidence of Birt Hogg Dub? syndrome (BHD) (14 tumours), 4) chromophobe renal cell carcinoma (ChRCC) (21 tumours) and 5) granular renal cell carcinoma (RCC) [64 tumours + 1 clear cell RCC (CRCC) with hyaline globules]. Ultrastructural analysis of tumour cells at the subcellular level was done using electron microscope (Philips electron microscope TEM 208) at the Department of Pathology, University Hospital in Plzen, Czech Republic. Cellular organelles and pigments were evaluated in 5 tumours from each group according to the simple random sample principle with a total of 30 analysed tumours. Results. In all analysed primary renal epithelial tumours with granular oncocytic, cytoplasm dominant organelles were mitochondria. Specific ultrastructural characteristics of RO were round mitochondria with lamellar cristae, whereas ChRCC had numerous typical cytoplasmic microvesicles 100?700 nm large and mitochondria with tubulovesicular, lamellar and circular cristae. Ultrastructural specificity of hybrid tumours were rare microvesicles and numerous mitochondria of O-PRCC mitochondria with lamellar cristae and small intracytoplasmic vesicles, 100?200 nm large, and of granular RCC, in addition to mitochondria, also glassy hyaline globules (GHG). Conclusion. Ultrastructural analysis indicates mitochondria as the dominant organelle in the analysed tumours. Electron microscopy showed specificities, i.e., differences in appearance of cristae, presence and size of vesicles as well as deposition of pigment in and out of cytoplasm and glassy hyaline globules.

Hybrid oncocytic/chromophobe renal cell tumor: An integrated genetic and epigenetic characterization of a case

IntroductionHybrid oncocytic/chromophobe tumor (HOCT) is a renal cell neoplasm displaying overlapping cellular and architectural features of both renal oncocytoma (RO) and chromophobe renal cell carcinoma (chRCC). It has been described in the context of oncocytosis, Birt-Hogg-Dubé syndrome, and also sporadically. Thus far, HOCT immunohischemical profile and cytogenetic alterations have been reported, but not epigenetic alterations. Herein, we characterize a HOCT case, including microRNA expression, comparing it to sporadic RO and chRCC. MethodsAn HOCT was entirely submitted. Representative paraffin blocks were selected for histochemical, immunohistochemical and FISH analyses. MicroRNAs were extracted from the two components separately and selected microRNA expression was performed. ResultsThis 4 cm HOCT, from a 69 year-old female, was composed mainly by oncocytic cells with an insular distribution (RO-like) and areas of larger clarified cells (chRCC-like). The two areas displayed different features: RO-like areas showed negative colloidal iron staining, multifocal CD15, negative CK7, focal multiple tetrasomies, and higher miR21 expression; chRCC-like areas showed colloidal iron diffuse staining with moderate intensity, focal CD15 and CK7, no numeric chromosomic alterations, and higher miR141 and miR200b expression. ConclusionmicroRNA expression in the two HOCT components is similar to its sporadic tumors counterparts. Morphologic, immunohistochemical, cytogenetic and epigenetic data on this case suggest either two independent pathogenic pathways or an early pathogenic divergence for RO-like and chRCC-like components of HOCT.

Interpretation of the fourth edition of WHO pathological classification of the thyroid tumors in 2017

In recent years, the incidence of thyroid carcinoma gradually increased in China. The pathology diagnosis and classification was based on WHO classification of Tumors of Endocrine Organs, the third edition which published in 2004. The fourth edition, WHO classification of Tumors of Endocrine Organs was published in July 2017. Compared with the third, some important aspects (or points) were revised: the ICD-O code of hyalinizing trabecular tumor was changed from 0 to 1; three other encapsulated follicular-patterned thyroid tumors were added; the variants of well differentiation thyroid carcinoma (including papillary carcinoma and follicular carcinoma ) which was originated from thyroid epithelial cells were updated; oncocytic cell tumors were separated from follicular tumors; the ICD-O code of ectopic thymoma was changed from 1 to 3. Refinement and standardization part of the concepts and diagnostic criterias were done which can solve practical problems in pathology diagnosis.

Oncocytes, Lymphocytes, Bicameral: Warthin’s Tumour

Oncocytes, Lymphocytes, Bicameral: Warthin’s Tumour

Pleomorphic Adenoma with Oncocytic Cells

A 28-year-old man with a 1-year asymptomatic increase in palatal volume showed a normal-colored, resilient swelling on the hard palate, measuring 4.0 × 2.5 cm in diameter. The CBCT showed intact palatine bone adjacent to an extensive, non-corticated, homogeneous enlarged area. Incisional biopsy revealed fibrous connective tissue with islets of epithelial cells; AE1/AE3 positive plasmacytoids, sometimes resulting in ductal formations; and accumulations of cells with clear/granular cytoplasm, suggestive of oncocytic cells, positive for AE1/AE3 focally to calponin and vimentin. The epithelial cells had a proliferation index of less than 5% with Ki67; were partially positive for CK7, 34BE12, and EMA; and negative for CK19, 1A4, GCDFP15, and p53. PAS and alcian blue staining revealed mucin in the salivary acini. The diagnosis was pleomorphic adenoma with oncocytic cells. Total enucleation of the lesion was performed with adipose graft from the cheek; within 35 days, the healing phase was exhibited.

Le carcinome rénal inclassé de bas grade à cellules éosinophiles, une entité récemment proposée dans le spectre des tumeurs rénales à cellules éosinophiles : étude d’un cas et discussion

Low-grade eosinophilic unclassified renal cell carcinoma is a rare kidney tumor recently described, not included in the WHO classification, which is very close to oncocytoma. It is unknown to most pathologists and clinicians. From a histopathological point of view, this tumor is composed of oncocytic cells arranged in a diffuse and solid pattern, without cell nests, that makes it possible to differentiate it from oncocytoma, and expresses cytokeratin 7 (CK7) heterogeneously. We report a case with a cranial vault metastasis, and present the features to differentiate this entity from oncocytoma. Furthemore, we discuss about unclassified renal cell carcinomas with oncocytic cells.

Analysis of histologic follow-up and risk of malignancy for salivary gland neoplasm of uncertain malignant potential proposed by the Milan System for Reporting Salivary Gland Cytopathology.

The Milan System for Reporting Salivary Gland Cytopathology is a tiered classification scheme that includes 6 diagnostic categories. Neoplasm, which is 1 of the 6 proposed categories, consists of benign neoplasm and neoplasm of uncertain malignant potential (NUMP). NUMP is reserved for a salivary gland neoplasm without clear distinction between benign and malignant. The objective of this study was to assess the risk of malignancy (ROM) of NUMP. A retrospective analysis was conducted on 656 salivary gland fine-needle aspiration specimens from 2010 to 2016. Cases that qualified as NUMP and had follow-up surgical resections were reviewed and reclassified into basaloid neoplasm (BN) and salivary gland neoplasm with predominant oncocytic cell (SGNOC) groups. The ROM for each group was calculated. Fifty-four salivary gland fine-needle aspirations of NUMP that had surgical follow-up were identified, which included 29 BNs and 25 SGNOCs. Histologic follow-up for the BN group identified 14 cellular pleomorphic adenomas, 5 basal cell adenomas, 2 benign cystadenomas, 3 adenoid cystic carcinomas, 3 epithelial and myoepithelial carcinomas, 1 basal cell adenocarcinoma, and 1 myoepithelial carcinoma. Histologic follow-up for the SGNOC group revealed 7 nodular oncocytoses, 6 Warthin tumors, 5 oncocytomas, 1 sebaceous adenoma, 1 mucinous cystadenoma, 2 acinic cell carcinomas, 2 mucoepidermoid carcinomas, and 1 mammary analog secretory carcinoma. The ROM was calculated at 24.1% for the NUMP category overall (27.6% for BNs and 20.0% for SGNOCs). The ROM of the SGNOC group is similar to that of the BN group but lower than the ROM (35%) proposed by the Milan system. Cancer Cytopathol 2018. © 2018 American Cancer Society.

Adrenal oncocytic pheochromocytoma with functionality in a neurofibromatosis patient: A case report

BackgroundThere are 4 prior reports of oncocytic pheochromocytoma of the adrenal. It may histologically resemble cortical carcinoma, which also can have oncocytic cells. Case presentationWe report a 54-year-old male with neurofibromatosis 1 who had an endocrinologically functional, 13.5 cm tumor. Histology showed mostly oncocytic cells. An adrenalectomy showed that the tumor had capsular and vascular invasion. Symptoms were cured by surgery. A cortical carcinoma with oncocytic change was initially favored, but the clinical history together with immunostain results were consistent with pheochromocytoma with oncocytic change. ConclusionsIn conclusion, the clinical history was crucial to the diagnosis. This is the first tumor of this type in a neurofibromatosis patient and the first in which functional effects were caused.

Papillary renal cell carcinoma with cytologic and molecular genetic features overlapping with renal oncocytoma: Analysis of 10 cases.

We present a series of papillary renal cell carcinomas (PRCC) reminiscent of so-called "oncocytic variant of papillary renal cell carcinoma" (OPRCC), included in the 2016 WHO classification as a potential type 3 PRCC. OPRCC is a poorly understood entity, cytologically characterized by oncocytic cells with non-overlapping low grade nuclei. OPRCC is not genotypically distinct and the studies concerning this variant have shown an inconsistent genetic profile. The tumors presented herein demonstrated predominantly papillary/tubulopapillary architecture and differed from OPRCC by pseudostratification and grade 2-3 nuclei (Fuhrman/ISUP). Because there is a morphologic overlap between renal oncocytoma (RO) and PRCC in the cases included in this study, the most frequently affected chromosomes in RO and PRCC were analyzed. 147 PRCC composed of oncocytic cells were retrieved from our registry in order to select a group of morphologically uniform tumors. 10 cases with predominantly papillary, tubulopapillary or solid architectural patterns were identified. For immunohistochemical analysis, the following antibodies were used: vimentin, antimitochondrial antigene (MIA), AMACR, PAX8, CK7, CK20, AE1-3, CAM5.2, OSCAR, Cathepsin K, HMB45, SDHB, CD10, and CD117. Enumeration changes of locus 1p36, chromosomes 7, 14, 17, X, Y and rearrangement of CCND1 were examined by FISH. For further study, only tumors showing karyotype similar to that of RO were selected. The tumors exhibiting either trisomy of chromosomes 7, 17 or gain of Y, thus abnormalities characteristic for PRCC, were excluded. There were 5 males and 5 females, with patient age ranging from 56 to 79 years (mean 66.8 years). The tumor size ranged from 2 to 10 cm (mean 5.1 cm). Follow-up was available for 8/10 patients (mean 5.2 years); one patient died of the disease, while 7 of 8 are alive and well. Immunohistochemically, all cases were reactive for AMACR, vimentin, PAX8, OSCAR, CAM5.2, and MIA. SDHB was retained in all cases. 9/10 cases were positive for CD10, 7/10 cases reacted with CK7, 4/10 with Cathepsin K, and 2/10 with AE1-3. None of the cases were positive for CD117, HMB45 and CK20. All 10 cases were analyzable by FISH and showed chromosomal abnormalities similar to that usually seen in RO (i.e. loss of 1p36 gene loci, loss of chromosome Y, rearrangement of CCND1 and numerical changes of chromosome 14). We analyzed a series of renal tumors combining the features of PRCC/OPRCC and RO, that included pseudostratification and mostly high grade oncocytic cells lining papillary/tubulopapillary structures, karyotype characterized by loss of 1p36, loss of chromosome Y, rearrangement of CCND1 gene and numerical changes of chromosome 14. Despite the chromosomal numerical abnormalities typical of RO, we classified these tumors as part of the spectrum of PRCC because of their predominant papillary/tubulopapillary architecture, immunoprofile that included reactivity for AMACR, vimentin and lack of reactivity for CD117, all of which is incompatible with the diagnosis of RO. This study expands the morphological spectrum of PRCC by adding a cohort of diagnostically challenging cases, which may be potentially aggressive.

Oncocytic Lesions of Salivary Glands with Morphological and Immunohistochemical Findings.

Objectives:Salivary gland neoplasms are less than 5% of all head and neck neoplasms (1). Although there are morphological similarities between different neoplasms, there may be catchy morphological differences in a single tumour. According to the World Health Organization (WHO), 4th Head and Neck Tumours Classification oncocytic salivary gland lesions are classified as nodular oncocytic hyperplasia, oncocytoma and oncocytic carcinoma. Oncocytic cells may be a component of other salivary gland neoplasms and metastatic malignities.Methods:In this study, salivary gland oncocytic lesions diagnosed in 2016-2017 were evaluated with Haematoxylin and Eosin (H&E) sections and PAS, diastase resistance PAS, p63, DOG1, cytokeratin7 (CK7), androgen receptor (AR) and PAX8 stains.Results:Nineteen cases were benign, two cases were malignant. Eighteen of the benign lesions were Warthin tumour (WT), one case was oncocytoma with nodular oncocytic hyperplasia. Acinic cell carcinoma (AciCCA) with oncocytic cells predominant was one of the malignant cases. The other case was high-grade salivary duct carcinoma (SDCA).Conclusion:The rarity and heterogeneity of this group of lesions may cause difficulties in diagnosis. We present histochemical and immunohistochemical findings of these lesions in light of the literature.

Adipose metaplasia of the thyroid associated with Hashimoto’s thyroiditis with nodular hyperplasia and oncocytic cells adenoma: case report and literature review

ABSTRACT Lesions involving adipose tissue and the thyroid gland are usually rare. In the present report, adipose metaplasia is associated with Hashimoto's thyroiditis with nodular hyperplasia and oncocytic adenoma in a 40-years-old female patient, which is one of the first reported cases of this association. The main clinical finding is the diffuse goiter, and the differential diagnosis must be performed to exclude the possibility of malignancies. The treatment is performed through total thyroidectomy. Thus, it is important the physicians be aware of this pathology with a view to a more effective clinical reasoning and to exclude more serious possibilities.

Contributions From University of Michigan 2016 New Frontiers in Pathology Conference.

Every autumn the Department of Pathology at the University of Michigan (UM; Ann Arbor, Michigan) organizes a case-based continuing medical education conference directed toward an audience of community and academic pathologists and trainees with the intent of providing up-to-date and cutting-edge information for the practicing pathologist. Last year the conference was held in Ann Arbor on October 19–21, 2016. Although we invited 3 excellent outside speakers, the meeting was primarily “homegrown,” with the majority of case studies and interactive breakout sessions presented by UM faculty. With gracious support from the editorial staff of Archives of Pathology & Laboratory Medicine, we publish 11 review articles based on topics presented at the conference. The manuscripts are published in 2 separate issues: part I in this issue and part II in the November issue.This issue (part I) contains 5 review articles that focus on surgical pathology. Reena Singh, MD, and Kathleen R. Cho, MD, present compelling evidence with molecular confirmation that the fallopian tubal epithelium can be a site of metastasis and not simply a site of origin for gynecologic cancers, especially in the face of widespread disease. Avneesh Gupta, MD, Nathan Shaller, MD, and Kathryn A. McFadden, MD, review the clinicopathologic features of pediatric thalamic brain tumors. Based upon their review of the literature, diffuse and pilocytic astrocytomas account for the vast majority of cases (80%). The authors emphasize the importance of tissue diagnosis for prognostication, therapeutic molecular targeting, and identifying tumors for which resection is likely to be beneficial. Julie M. Jorns, MD, and her colleagues from radiology and oncologic surgery, Deborah O. Jeffries, MD, and Lesly A. Dossett, MD, MPH, highlight next-generation technologies in localization for breast surgery, notably nonradioactive, nonwire localization techniques such as SAVI SCOUT (Cianna Medical, Inc, Aliso Viejo, California), which uses infrared light and microimpulse laser, and Magseed (Endomagnetics, Inc, Austin, Texas), which uses a magnetic seed for localization, both of which are also being tested and deployed at other institutions. Shula Schechter, MD, and Jiaqi Shi, MD, PhD, review the clinicopathologic and molecular features of the pancreatic simple mucinous cyst, an underrecognized lesion, which they compare and contrast with other pancreatic mucinous cysts, notably intraductal papillary mucinous neoplasm and mucinous cystic neoplasm, tumors that differ from simple mucinous cysts in that they are associated with malignant potential. Finally, in this issue Angela Wu, MD, details UM's approach to the very challenging diagnosis of oncocytic renal cell neoplasia in core biopsy and resection specimens using morphologic and immunohistochemical criteria.In next month's issue (part II), review articles will appear on additional topics presented at the UM New Frontiers Conference in hematopathology, dermatopathology, and perinatal and soft tissue pathology. There are 3 hematopathology papers. In one, Nathan J. Charles, MD, PhD, and Daniel F. Boyer, MD, PhD, review mixed-phenotype acute leukemia, an underrecognized, heterogeneous category that comprises acute leukemias with discrete admixed populations of myeloid and lymphoid blasts and ones with extensive coexpression of lymphoid and myeloid markers in a single blast population. In the second hematopathology paper, Vivian M. Hathuc, DO, Alexandra C. Hristov, MD, and Lauren B. Smith, MD, review primary cutaneous acral CD8+ T-cell lymphoma, a newly classified cutaneous lymphoma with an indolent clinical course, and compare and contrast it with other more aggressive cutaneous T-cell diseases. Steven Weindorf, MD, and John Frederiksen, MD, PhD, present a thorough yet concise review of IgG4-related disease for the practicing pathologist in the third hematopathology paper. Also in the November issue, Amer Heider, MD, reviews placental pathology of fetal vascular malperfusion in a very well-written and accessible paper; Lauren M. Stanoszek, MD, PhD, Grace Y. Wang, MD, and Paul W. Harms, MD, PhD, address diagnostic mimics of cutaneous basal cell carcinoma in their beautifully illustrated manuscript; and David R. Lucas, MD, reviews and updates myxoinflammatory fibroblastic sarcoma, a challenging soft tissue tumor that is frequently misdiagnosed by pathologists unaware of its clinicopathologic manifestations.We hope you enjoy reading these articles.

Mitochondrial DNA “common deletion” in post–fine needle aspiration infarcted oncocytic thyroid tumors

Thyroid fine needle aspiration (FNA) can rarely induce morphological changes potentially hindering the histopathological diagnosis, especially in Hurthle cell tumors (HCTs), which may easily undergo post-FNA infarction or necrosis. HCTs contain mitochondrion (mt)-rich cells that may bear mtDNA mutations, the most frequent being the so-called common deletion (CD). The aim of this study was to determine the presence and extent of the mtDNA CD in a series of thyroid HCTs that underwent extensive infarction following FNA procedure in comparison with a control series of HCTs lacking post-FNA ischemic/hemorrhagic alterations. Of 257 HCTs with available matched FNA and surgical specimens, 8 cases showed extensive (≥80%) infarction or necrosis in the resected nodule (4 adenomas, 1 carcinoma, 3 HCTs undefined for malignancy). Noninfarcted tumors in the control series included 9 adenomas, 1 carcinoma, and 1 follicular tumor of uncertain malignant potential. These lesions were significantly (P = .03) larger than infarcted nodules. The mtDNA CD was identified using semiquantitative real-time polymerase chain reaction in 2 of 8 (25%) infarcted tumors. In HCTs lacking infarction/necrosis of the control series, the CD was significantly (P = .05) more common (8/11 cases, 72.7%). In 7 of the 10 deleted cases, the CD was present also in the adjacent nonneoplastic parenchyma. In conclusion, the rare oncocytic tumors undergoing extensive infarction are smaller than those lacking ischemic changes and bear the mtDNA CD in a significantly lower proportion compared with control noninfarcted HCTs. This may suggest that mtDNA deletion confers a survival advantage to oncocytic cells in stress conditions, including FNA procedures.

Nodular oncocytic hyperplasia: Can cytomorphology allow for the preoperative diagnosis of a nonneoplastic salivary disease?

Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is a benign process that does not inherently require surgical excision. However, cytologic findings in fine-needle aspiration (FNA) of oncocytosis cases have not been well characterized previously, limiting preoperative identification. All available cases of oncocytosis with corresponding FNA specimens were identified from the pathology archives of 3 academic institutions. Clinical, cytologic, and histologic findings were tabulated for all cases. Twelve cases of oncocytosis were identified from 11 patients, including 11 parotid FNA specimens and 1 submandibular FNA specimen. On the original diagnoses, 6 specimens were classified as benign, 4 as atypical, and 2 as nondiagnostic. Oncocytosis was listed in the differential diagnosis in only 1 case. Among diagnostic aspirates, 8 demonstrated low cellularity and 2 demonstrated moderate cellularity. All 10 cases demonstrated oncocytic cells in small to medium groups, with single cells in just 1 case. Spindled and squamous morphology were each noted in 3 cases. Four cases demonstrated cystic change and 1 showed background mucin without goblet cells. No necrosis or mitoses were observed. Although oncocytosis demonstrates some overlap with Warthin tumor and oncocytoma, it lacks the diagnostic findings specific to oncocytic salivary gland malignancies such as salivary duct carcinoma, acinic cell carcinoma, mammary analog secretory carcinoma, and mucoepidermoid carcinoma. Despite current limitations in the understanding of oncocytic salivary gland lesions, the presence of a paucicellular specimen comprised of small groups of oncocytic cells should raise the possibility of oncocytosis in the differential diagnosis and can favor it in elderly patients with multiple salivary nodules. Cancer Cytopathol 2017;125:627-34. © 2017 American Cancer Society.

Fine needle cytology pre-surgical differentiation of parathyroid neoplasms: Is it reliable?

Fine needle cytology (FNC) of a parathyroid neoplasia (PN) is reliable, but needs to be confirmed by Parathormone (PTH) and Thyroglobulin (TG) immunoassay on needle washing or by immunocytochemistry (ICC) evaluation. The differentiation between parathyroid adenoma (PA), atypical adenoma (PAA) and carcinoma (PC) is difficult on histology or even impossible on FNC. The aim of this study was to evaluate possible cytological criteria to classify FNC-PN further. Twenty-three FNC samples of PN and parathyroid cysts were rather then have been reviewed. The series includes 18 PNs, 4 cysts and 1 Thyr3B (histologically diagnosed as PA). Cytological features were: cellularity, patterns (follicular, solid or papillary), clear, oncocytic, isolated cells, nuclear atypia, cytoplasmic inclusions, nucleoli and mitoses. Data were compared with the histological controls. Seventeen PNs, 2 cysts and 1 Thyr3B FNC samples were histologically diagnosed as PA (16), PAA (2) and PC (2). Two cysts and 1 PN were not confirmed histologically. Cytological features and incidences were: high cellularity (1 PA, 1 PAA, 2 PCs), follicular (8 PAs, 1 PAA), solid (5 PAs, 1 PC), papillary pattern (1PA, 1 PAA, 1 PC), clear cells (4 PAs, 1 PAA, 2 PCs), oncocytic cells (6 PAs, 1 PAA, 2 PCs), isolated cells (5 PAs, 2 PAAs, 2 PCs), nuclear atypia (2 PAs, 1 PAA, 2 PCs), cytoplasmic inclusions (4 PAs, 2 PCs), nucleoli (2 PCs) and mitoses (2 PCs). Evident nucleoli and mitoses may suggest the differentiation between PA and PC. However, further investigations are required to confirm these preliminary observations.

Warthin-like papillary renal cell carcinoma: Clinicopathologic, morphologic, immunohistochemical and molecular genetic analysis of 11 cases.

Oncocytic papillary renal cell carcinoma (PRCC) is a distinct subtype of PRCC, listed as a possible new variant of PRCC in the 2016 WHO classification. It is composed of papillae aligned by large single-layered eosinophilic cells showing linearly arranged oncocytoma-like nuclei. We analyzed clinicopathologic, morphologic, immunohistochemical and molecular-genetic characteristics of 11 oncocytic PRCCs with prominent tumor lymphocytic infiltrate, morphologically resembling Warthin's tumor. The patients were predominantly males (8/11, 73%), with an average age of 59years (range 14-76), and a mean tumor size of 7cm (range 1-22cm). Tumors had the features of oncocytic PRCCs with focal pseudostratification in 8/11 cases and showed dense stromal inflammatory infiltration in all cases. Papillary growth pattern was predominant, comprising more than 60% of tumor volume. Tubular and solid components were present in 5 and 3 cases, respectively. Uniform immunohistochemical positivity was found for AMACR, PAX-8, MIA, vimentin, and OSCAR. Tumors were mostly negative for carboanhydrase 9, CD117, CK20, and TTF-1. Immunohistochemical stains for DNA mismatch repair proteins MLH1 and PMS2 were retained in all cases, while MSH2 and MSH6 were negative in 1 case. Tumor infiltrating lymphocytes (TILs) consisted of both B and T cells. Chromosomal copy number variation analysis showed great variability in 5 cases, ranging from a loss of one single chromosome to complex genome rearrangements. Only one case showed gains of chromosomes 7 and 17, among other aberrations. In 4 cases no numerical imbalance was found. Follow up data was available for 9 patients (median 47.6months, range 1-132). In 6 patients no lethal progression was noted, while 3 died of disease. In conclusion, Warthin-like PRCC is morphologically very close to oncocytic PRCC, from which it differs by the presence of dense lymphoid stroma. Chromosomal numerical aberration pattern of these tumors is variable; only one case showed gains of chromosomes 7 and 17. Warthin-like PRCC is a potentially aggressive tumor since a lethal outcome was recorded in 3/9 cases.

Heterogeneous Periostin Expression in Different Histological Variants of Papillary Thyroid Carcinoma.

Background Periostin (PN) epithelial and stromal overexpression in tumor pathology has been studied according to tumor growth, angiogenesis, invasiveness, and metastasis, but a limited number of studies address PN in thyroid tumors. Aim Our study aimed to analyze PN expression in different histological variants of PTC and to correlate its expression with the clinicopathological prognostic factors. Material and Methods PN expression has been immunohistochemically assessed in 50 cases of PTC (conventional, follicular, oncocytic, macrofollicular, and tall cell variants), in tumor epithelial cells and intratumoral stroma. The association between PN expression and clinicopathological characteristics has been evaluated. Results Our results show that PTC presented different patterns of PN immunoreaction, stromal PN being significantly associated with advanced tumor stage and extrathyroidal extension. No correlations were found between PN overexpression in tumor epithelial cells and clinicopathological features, except for specific histological variants, the highest risk of poor outcome being registered for the conventional subtype in comparison to the oncocytic type. Conclusions Our study demonstrates differences in PN expression in histological subtypes of PTC. Our results plead in favor of a dominant protumorigenic role of stromal PN, while the action of epithelial PN is less noticeable.

オンコサイト様乳頭状腎細胞癌出血を契機に透析導入となった結節性硬化症の1例

オンコサイト様乳頭状腎細胞癌出血を契機に透析導入となった結節性硬化症の1例

Cardiolipins Are Biomarkers of Mitochondria-Rich Thyroid Oncocytic Tumors.

Oncocytic tumors are characterized by an excessive eosinophilic, granular cytoplasm due to aberrant accumulation of mitochondria. Mutations in mitochondrial DNA occur in oncocytic thyroid tumors, but there is no information about their lipid composition, which might reveal candidate theranostic molecules. Here, we used desorption electrospray ionization mass spectrometry (DESI-MS) to image and chemically characterize the lipid composition of oncocytic thyroid tumors, as compared with nononcocytic thyroid tumors and normal thyroid samples. We identified a novel molecular signature of oncocytic tumors characterized by an abnormally high abundance and chemical diversity of cardiolipins (CL), including many oxidized species. DESI-MS imaging and IHC experiments confirmed that the spatial distribution of CLs overlapped with regions of accumulation of mitochondria-rich oncocytic cells. Fluorescent imaging and mitochondrial isolation showed that both mitochondrial accumulation and alteration in CL composition of mitochondria occurred in oncocytic tumors cells, thus contributing the aberrant molecular signatures detected. A total of 219 molecular ions, including CLs, other glycerophospholipids, fatty acids, and metabolites, were found at increased or decreased abundance in oncocytic, nononcocytic, or normal thyroid tissues. Our findings suggest new candidate targets for clinical and therapeutic use against oncocytic tumors. Cancer Res; 76(22); 6588-97. ©2016 AACR.