Oncocytes Research Articles

Melanotic Oncocytic Metaplasia of the Nasopharynx Seen as a Rare Form of Cystic Mass: A Case Report and Review of the Literature

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare benign lesion which is characterized by the presence of usually a small, pigmented lesion near the Eustachian tube opening, but never reported the form of cyst without pigmentation. A 76-year-old man who had a symptom with globus pharyngeus for 3 months was presented to otolaryngology clinic. The lesion was found as a rare form of cystic mass without pigmentation through endoscopic examination. Microscopically, there were well-formed glandular structured oncocytic cells with abundant eosinophilic granular cytoplasm. Scattered brown pigments were also noted, which were positive for S-100 and negative for HMB-45 in immunohistochemistry. He was diagnosed with MOM of the nasopharynx. MOM of the nasopharynx should be always taken into consideration about its various clinical forms as a benign mimicker of malignant melanoma.

Warthin like Variant of Papillary Thyroid Carcinoma: A Rare Variant

Introduction: Warthin like papillary thyroid carcinoma is a rare variant that bears features similar to Warthin tumour of salivary gland. It shows papillary or follicular structures lined by oncocytic cells having typical nuclear features of papillary thyroid carcinoma and marked lymphoplasmacytic infiltrate in the stroma. Case Report: A 60 year old lady presented in the ENT OPD with right sided neck swelling since 2 years. On examination the swelling was firm, non-tender, moving with deglutition and measured 4x3 cm. FNA smears of the swelling were highly cellular and comprised of cells arranged in papillary clusters. The cells were predominantly oncocytic and showed nuclear grooving and intranuclear inclusions. Cytological diagnosis of papillary thyroid carcinoma (Bethesda Category VI) was offered. Thyroidectomy specimen measured 6.5x5x3 cm and right lobe revealed gray tan tumor with numerous papillae and few cystic areas. Microscopy revealed a well circumscribed tumour, with tumour cells arranged in papillary architecture with presence of dense lymphoplasmacytic infiltrate in the stalks of papillae. The cells lining the papillae had abundant granular eosinophilic cytoplasm and many of the cells showed nuclear grooving and intranuclear inclusions. Occasional psammoma bodies were also seen. The surrounding thyroid showed features of hashimoto’s thyroiditis. A final diagnosis of Warthin like variant of papillary thyroid carcinoma was given. Conclusion: Warthin like variant of papillary thyroid carcinoma is a distinct rare variant. It is associated with good prognosis when compared with other variants of papillary thyroid carcinoma, warranting a proper identification.

The differences in distant metastatic patterns and their corresponding survival between thyroid cancer subtypes.

This study aimed to systematically elucidate the metastatic patterns and their corresponding survival of each thyroid cancer subtype at time of diagnosis. We accessed the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2018 to search for primary thyroid cancers with DM at presentation (M1). We included 2787 M1 thyroid cancers for statistical analyses and the incidence of DM at presentation was 2.4%. Lung was the most common metastatic site for anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), papillary thyroid carcinoma (PTC), and oncocytic (Hurthle) cell carcinoma (HCC) whereas bone is the favorable disseminated site of follicular thyroid carcinoma (FTC) and medullary thyroid carcinoma (MTC). Patients with multi-organ metastases had the worst survival whereas bone metastases were associated with a favorable outcome (p< 0.001). There are significant differences in DM patterns of thyroid cancer subtypes and their corresponding survival.

Diagnostic significance of CyclinD1 and D2-40 expression for follicular neoplasm of the thyroid

ObjectivesTo evaluate the expression and differential diagnostic significance of CyclinD1 and D2–40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. MethodsA total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2–40 was performed. ResultsWe found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2–40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2–40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2–40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). ConclusionsCyclinD1 and D2–40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

Pleomorphic adenoma: detection of PLAG1 rearrangement–positive tumor components using whole-slide fluorescence in situ hybridization

Pleomorphic adenoma (PA) consists of heterogeneous histological architecture mixed with epithelioid and mesenchymal forms. Various types of epithelial or myoepithelial malignancies arise from PA, but sarcomas are extremely rare. A human androgen receptor gene (HUMARA) clonality assay has suggested that PA is clonal in nature. However, clonality of various tumor components of PA would be difficult to determine with this assay. In addition, the results obtained should be carefully interpreted. PLAG1 rearrangements are considered a good molecular marker for neoplasticity in PA. We aimed to clarify the neoplasticity of the various tumor components present in PA using whole-slide fluorescence in situ hybridization (FISH). Five PA cases positive for PLAG1 rearrangements were examined. Using an immunohistochemistry panel, cell components in PA were classified into eight cell types. To precisely localize PLAG1 rearrangement-positive cell components at the cellular level, sequential retrieval of whole-slide imaging (WSI) data of HE histology and FISH for PLAG1 rearrangement was carried out. PLAG1 rearrangements were detected in ductal cells, myoepithelial spindle cells, myoepithelial oncocytic cells, myoepithelial plasmacytoid cells, and mesenchymal chondroid cells, but not in mesenchymal lipid cells, mesenchymal fibrous cells, or vascular endothelial cells. Immunohistochemical PLAG1 expression was restricted to cell components harboring PLAG1 rearrangements.The results of the present study indicate that ductal and myoepithelial, chondroid cells are neoplastic but lipid, fibrous, and endothelial cells are not. PLAG1 immunohistochemistry is useful in discriminating neoplastic from non-neoplastic cell components. These findings may be important for elucidating tumorigenesis and the process of malignant transformation in PA.

Lysosomal and cytoskeletal events in epithelial salivary tumours as assessed by imunohistochemistry for CD63 and HSP27

Little attention has been paid to immunohistochemically assessed, lysosomal activities in salivary neoplasia. In an attempt to remedy this, the present investigation applied immunohistochemistry for CD63 antigen (a lysosomal membranous protein) and HSP27 (a molecular chaperone with roles in intracellular homeostasis) to archival paraffin-embedded surgical specimens of 101 benign and malignant, epithelial salivary tumours. Diffuse cytoplasmic CD63 immunoreactivity was seen in serous cells in acinic cell carcinoma, and mucous cells in mucoepidermoid carcinoma, pleomorphic adenoma (PA) and Warthin tumour. Apical rims or bands of CD63 immunoreactivity were also seen in simple cells lining tubular structures in PA, acinic cell carcinoma, mucoepidermoid carcinoma and polymorphous (low-grade) adenocarcinoma; and, occasionally, oncocytic luminal cells in Warthin tumour. HSP27 immunoreactivity was usually seen in non-luminal cells of PA, basal cells of oncocytic tumours, epidermoid cells of mucoepidermoid carcinoma and PA, and cells outlining aggregates or pseudolumina of adenoid cystic carcinoma. Expression of CD63 is preferentially associated with differentiated or simple luminal cell phenotypes in epithelial salivary tumours and possibly reflects autophagy of secretory granules or absorption of luminal material. Expression of HSP27 is preferentially associated with non-luminal cells and possibly reflects remodelling of the cytoskeleton.

Papillary thyroid carcinoma tall cell variant shares accumulation of mitochondria, mitochondrial DNA mutations, and loss of oxidative phosphorylation complex I integrity with oncocytic tumors.

Papillary thyroid carcinoma tall cell variant (PTC‐TCV), a form of PTC regarded as an aggressive subtype, shares several morphologic features with oncocytic tumors. Pathogenic homoplasmic/highly heteroplasmic somatic mitochondrial DNA (mtDNA) mutations, usually affecting oxidative phosphorylation (OXPHOS) complex I subunits, are hallmarks of oncocytic cells. To clarify the relationship between PTC‐TCV and oncocytic thyroid tumors, 17 PTC‐TCV and 16 PTC non‐TCV controls (cPTC) were subjected to: (1) transmission electron microscopy (TEM) to assess mitochondria accumulation, (2) next‐generation sequencing to analyze mtDNA and nuclear genes frequently mutated in thyroid carcinoma, and (3) immunohistochemistry (IHC) for prohibitin and complex I subunit NDUFS4 to evaluate OXPHOS integrity. TEM showed replacement of cytoplasm by mitochondria in PTC‐TCV but not in cPTC cells. All 17 PTC‐TCV had at least one mtDNA mutation, totaling 21 mutations; 3/16 cPTC (19%) had mtDNA mutations (p < 0.001). PTC‐TCV mtDNA mutations were homoplasmic/highly heteroplasmic, 16/21 (76%) mapping within mtDNA‐encoded complex I subunits. MtDNA mutations in cPTC were homoplasmic in 2 cases and at low heteroplasmy in the third case, 2/3 mapping to mtDNA‐encoded complex I subunits; 2/3 cPTC with mtDNA mutations had small tall cell subpopulations. PTC‐TCV showed strong prohibitin expression and cPTC low‐level expression, consistent with massive and limited mitochondrial content, respectively. All 17 PTC‐TCV showed NDUFS4 loss (partial or complete) and 3 of 16 cPTC (19%) had (partial) NDUFS4 loss, consistent with lack of complex I integrity in PTC‐TCV (p < 0.001). IHC loss of NDUFS4 was associated with mtDNA mutations (p < 0.001). Four BRAF V600E mutated PTCs had loss of NDUSF4 expression limited to neoplastic cell subpopulations with tall cell features, indicating that PTCs first acquire BRAF V600E and then mtDNA mutations. Similar to oncocytic thyroid tumors, PTC‐TCV is characterized by mtDNA mutations, massive accumulation of mitochondria, and loss of OXPHOS integrity. IHC loss of NDUFS‐4 can be used as a surrogate marker for OXPHOS disruption and to reliably diagnose PTC‐TCV.

An aggressive case of Warthin-like variant of papillary thyroid carcinoma (PTC)

Abstract Introduction/Objective Warthin-like variant of PTC is a rare subtype of PTC, characterized by papillary growth lined with oncocytic neoplastic cells and lymphocytic rich stroma in the stalks of the papillae. It is frequently associated with Hashimoto thyroiditis and has good prognosis due to lower risk of metastasis. An association with BRAF V600E mutation has been reported. Here we report an aggressive case of Warthin-like variant of PTC. Methods/Case Report A 33-year-old Hispanic female presented with a progressively expanding neck mass, difficulty swallowing, voice hoarseness, and neck pain. Ultrasound showed a 3.8 cm left thyroid nodule which on biopsy was positive for PTC. Laboratory tests were positive for anti-peroxidase and anti-thyroglobulin antibodies. A total thyroidectomy was performed. Grossly, the left thyroid lobe nodule was well-circumscribed, unencapsulated, and firm with solid homogenous gray-tan cut surface. Microscopically, the nodule consisted of large eosinophilic cells demonstrating characteristic PTC nuclear features, arranged in papillary structures with the cores packed with prominent lymphoplasmacytic infiltrate consistent with Warthin-like variant of PTC (figure). Separate sub-centimeter foci of PTC with similar features were identified in a background of chronic lymphocytic thyroiditis. Central and left neck dissection showed extensive lymph node metastasis which had features similar to the primary tumor but with less pronounced lymphoplasmacytic cores. The patient is currently 6-month post operation and is receiving iodine ablative therapy. Results (if a Case Study enter NA) NA Conclusion Molecular analysis of the tumor may aid in identifying molecular aberrations responsible for the aggressive nature in this case and potentially guide treatment.

Clinical, Pathological, and Genomic profiles of Salivary Warthin tumor-like Mucoepidermoid Carcinoma

Abstract Introduction/Objective Warthin tumor-like mucoepidermoid carcinoma(WTL- MEC) is one of the subvariant of mucoepidermoid carcinoma. It mimics the histological features of metaplastic Warthin tumors (mWTs). To investigate the clinicopathological, molecular features, and bio-behaviors of WTL-MEC, we retrospected a cohort of 29 WTL- MEC patients. Methods/Case Report The clinicopathological and microscopic data were collected. Dual-color FISH analysis was performed on paraffin-embedded sections of 29 WTL- MEC patients and 16 mWTs patients using a MAML2 break- apart probe. Whole-exome sequencing and whole transcription sequencing were performed on 3 WTL-MEC and 3 typical mucoepidermoid carcinomas (TMEC) patients. Genetic data were bioinformatically analyzed by software MuTect (v1.7), PINDEL (v0.2.5), SnpEff (v3.0), and etc. Results (if a Case Study enter NA) The cohort of WTL-MEC included 10 male and 19 female patients with a median age of 42.3 years (range, 8 to 68 years). Microscopically, the WTL-MEC lesion consisted of multi-cysts with variant shapes and sizes. The cystic spaces were lined by bi-layered and multilayered oncocytic cells. A transition zone between the bi-layered oncocytic epithelium to the multilayered oncocytic epithelium was observed in WTL-MEC. The cords of epidermoid cells and mucous cells could be found. The germinal center, extensive hyalinization, and mucus extravasation were observed. MAML2 rearrangement was identified in 29 (100%) WTL-MEC. No rearrangement was observed in mWTs by FISH. MET was the most commonly mutated gene in TMEC, and PRDM11 was the most commonly mutated gene in WTL-MEC. Twenty-nine patients were alive without recurrent at the end of the follow-up periods(5–128M). One Patient died due to the metastasis to the lung. Conclusion compared with mWTs, WTL- MEC usually presented in the young, non-smoking female. The histological feature of WTL-MEC depended mainly on the transition zone of the bi-layered oncocytic epithelium and the multilayered oncocytic epithelium. And MAML2 status can confirm the diagnosis. CRTC1-MAML2 and PRDM11 mutations appear to be the main driver event of WTL-MEC. Prognosis was usually favorable, but recurrence or metastasis may rarely occur.

Low-grade oncocytic tumour expands the spectrum of renal oncocytic tumours and deserves separate classification: a review of 23 cases from a single tertiary institute

AimsLow-grade oncocytic tumour (LOT) has recently been introduced as a potential distinct entity.MethodsAt the Indiana University department of pathology, primary renal epithelial neoplasms between 2005 and 2020 were searched after...

Renal oncocytoma in a female patient with rheumatoid arthritis and secondary Sjögren’s syndrome: Non-coincidental link to autoimmunity?*

The objective of the article was to describe a female patient with rheumatoid arthritis (RA) and secondary Sjogren’s syndrome (SS) who developed a renal oncocytoma and was cured by percutaneous cryoablation therapy. A 72-year-old female patient with a long-term history of polyarthritis involving her hands, shoulders, knees, and ankles associated with morning stiffness and rheumatoid factor of 107 U/mL (nr: <29 U/mL) and anti-CCP of 121 U/mL (nr:<5 U/mL). A diagnosis of RA was determined 10 years ago, and prednisone with methotrexate were initiated, later changed for leflunomide 20mg/day. In 2014 a diagnosis of secondary SS was determined. In April 2014, during a routine abdominal ultrasound, a tumor was found in her left kidney. A magnetic resonance imaging confirmed a solid nodule with hypervascularization on the left kidney. She was submitted to a percutaneous cryoablation procedure without any intercurrence, and it had success. The histopathological analysis demonstrated a renal oncocytoma limited to the left kidney. No chemotherapy or radiotherapy was needed. After surgery, a flare of RA was noted and was resistant to methotrexate and sulfasalazine. Rituximab was then started, and she had an excellent progressive response. Minor thyroid changes were registered by ultrasound monitoring and signs of hyperparathyroidism manifested. This observation illustrates the first ever described case of a patient with RA and secondary SS who developed several years after the RA onset, a renal oncocytoma, and was successfully treated with cryoablation therapy. The possible links between oncocytic cell metaplasia/neoplasia and autoimmunity are discussed.

Malignancy Risk in 18F-FDG-Avid Thyroid Incidentalomas: Controversies and Limitations

Introduction: The prevalence of malignancy in thyroid incidentalomas (TI) discovered on 18F-FDG-PET or PET/CT varies between 0% and 63.6%. The pooled malignancy rate according to three systematic reviews is 33-35%. The 2015 American Thyroid Association (ATA) guidelines recommend that such nodules, when one centimeter or larger in size, should undergo further investigation with thyroid ultrasound (US) and fine-needle aspiration (FNA) cytology. Objectives: The objective of our study was to determine the rate of malignancy amongst TI discovered incidentally on 18F-FDG-PET or PET/CT, examine their clinicopathologic characteristics, and assess the usefulness of maximum standardized uptake values (SUVmax) in differentiating benign and malignant lesions. Methods: We performed an electronic medical record search looking at all 18F-FDG-PET or PET/CT reports during the study period of 12/01/2015 to 05/31/2019 that included the keyword ‘thyroid’ in the impression. Exclusion criteria included a history of thyroid disease or malignancy, known lesion(s) detected on previous clinical or radiological examinations and diffuse radiotracer uptake. Of the 476 reports reviewed, 136 cases were included in the study. Results: Common indications included initial staging or restaging of lymphoma (diffuse large B-cell, mantle-cell, T-cell types) (27.9%), lung adenocarcinoma (18.4%), head and neck cancer (16.9%) and breast cancer (11%). Fifty-eight (42.6%) patients had metabolically inactive lesions; five (8.6%) underwent further investigation with thyroid US and 3 subsequently with FNA (5%). All 3 had benign cytology. Seventy-seven (56.6%) patients had metabolically active lesions and 25 (32.5%) underwent imaging with thyroid US. Twelve (15.6%) had FNA; eight (66.7%) had benign cytology, two (16.7%) revealed atypia of undetermined significance and two (16.7%) were malignant. Biopsy for the two patients with malignant cytology showed follicular cell neoplasm of oncocytic hurtle cell type, and invasive follicular carcinoma with focal insular and papillary features and extensive capsular and vascular invasion. The mean SUVmax in malignant vs benign lesions was 9.05 and 6.41 respectively. Conclusion: The malignancy rate was 2.6% amongst all patients with 18F-FDG-avid TI and 8% amongst patients with metabolically active lesions who were investigated with thyroid US+/- FNA. This is significantly lower than malignancy rates previously reported in the literature. The evident inhomogeneity in the literature is likely multifactorial and may be explained in part by a dissimilarity among studies, and an informed decision by some to avoid invasive testing in the context of poor prognosis from underlying non-thyroidal cancer. Research is needed to determine the cohort of patients who could potentially benefit from further evaluation and treatment.

Oncocytic Papillary Renal Cell Carcinoma in an 11-year-old girl

Oncocytic Papillary Renal Cell Carcinoma (OPRCC) is a rare variant of renal cell carcinoma with overlapping characteristics type 1 and 2 of papillary renal carcinoma. Based on the literature, OPRCC is predominantly present in adult males. OPRCC has a specific genetic affiliation with the Fumarate Hydratase gene requiring all patients diagnosed with OPRCC to undergo genetic testing. There isn't any agreement for the treatment of OPRCC due to the rarity of the disease; however, a radical nephrectomy poses as a possible modality. Therefore, we present the rare case of an 11-year-old female found to have OPRCC.

Renal cell carcinomas with tubulopapillary architecture and oncocytic cells: Molecular analysis of 39 difficult tumors to classify

So-called oncocytic papillary renal cell carcinoma (OPRCC) is a poorly defined variant of papillary renal cell carcinoma. Since its first description, several studies were published with conflicting results, and thus precise definition is lacking.A cohort of 39 PRCCs composed of oncocytic cells were analyzed. Cases were divided into 3 groups based on copy number variation (CNV) pattern. The first group consisted of 23 cases with CNV equal to renal oncocytoma. The second group consisted of 7 cases with polysomy of chromosomes 7 and 17 and the last group of 9 cases included those with variable CNV.Epidemiologic, morphologic and immunohistochemical features varied among the groups. There were not any particular histomorphologic features correlating with any of the genetic subgroups. Further, a combination of morphologic, immunohistochemical, and molecular-genetic features did not allow to precisely predict biologic behavior.Owing to variable CNV pattern in OPRCC, strict adherence to morphology and immunohistochemical profile is recommended, particularly in limited samples (i.e., core biopsy). Applying CNV pattern as a part of a diagnostic algorithm can be potentially misleading.OPRCC is a highly variable group of tumors, which might be misdiagnosed as renal oncocytoma. Using the term OPRCC as a distinct diagnostic entity is, thanks to its high heterogeneity, questionable.

Thyroid Oncocytic Cell in Cytological and Histologic Reports: Institutional Experience

Purpose: Oncocytic cell tumors, due to historical and clinical reasons, tend to be put in a higher risk category compared with other cell type tumors. We tried to define the malignancy risk for this entity. Methods: At our institution, we studied the risk of malignancy associated with a cohort of 107 thyroid nodules aspirates containing oncocytic cells in the cytology report and we have further analyzed other clinical factors. Results: A tendency for higher risk of malignancy in male sex was found (31.3% vs. 15.4% in women), the difference, however, was not statistically significant (P = 0.291). Total thyroidectomy was the preferred surgical approach and only 10.3% of patients were submitted to lobectomy. Histopathology reports documented 46.7% hyperplastic/adenomatoid nodules, 31.8% adenomas, 12.1% papillary carcinoma, 3.7% oncocytic cell carcinoma, 2.8% lymphocytic thyroiditis and 1.9% poorly differentiated carcinoma. Benign nodules (Bethesda Class II) exhibited a 9.7% malignancy risk; Class III exhibited a 20% malignancy risk; Class IV exhibited a 18.4% malignancy; Class V exhibited a 16% malignancy risk and Class VI exhibited a 100% malignancy risk. Overall histologic data from the aspirated nodules showed a risk of malignancy of 17.8%. Conclusion: Our study seems to suggest that in the presence of oncocytic cells there may be a tendency for a higher than expected malignancy rate. Clinical factors appear to be insufficient to base our management decisions with confidence and molecular markers are still under development. Therefore, surgery may stand as the favored option in this setting.

Current Understanding of Papillary Thyroid Carcinoma

The term thyroid neoplasm incorporates tumors that originate from follicular cells and those that arise from parafollicular cells (C cells). Differentiated thyroid cancer, which originates from follicular cells, includes papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), oncocytic cell carcinoma (Hürthle), poorly differentiated carcinoma, and anaplastic thyroid carcinoma (ATC). PTC tends to have an indolent clinical course with low morbidity and mortality. However, this entity has a broad range of biological and clinical behavior that can result in disease recurrence and death, depending on patient and tumor characteristics and the initial treatment approach. PTC is the most common form of well-differentiated thyroid cancer (WDTC) and based on the most recent statistics, accounts for approximately 89.4% of all thyroid malignancies. PTC appears as an irregular solid or cystic nodule in normal thyroid parenchyma. PTC has the propensity for lymphatic invasion, but it is less likely to have hematogenous spread. Around 11% of patients with PTC present with distant metastases outside the neck and mediastinum. This manuscript with review the current understanding of the epidemiology, pathology, molecular characteristics, prognostic factors, and dynamic risk stratification of PTC centered on an evidence-based and personalized approach.

Papillary‐cystic neoplasms of the middle ear are distinct from endolymphatic sac tumours

Papillary neoplasms of the middle and inner ear are rare and poorly characterised. The current World Health Organization classification divides them into two major subtypes: aggressive papillary tumours (APTs) and endolymphatic sac tumours (ELSTs). The aim of this article is to present two papillary neoplasms of the middle ear that do not fit into either the classic APT category or the classic ELST category, and compare them with three ELSTs. The patients were a 48-year-old female and a 59-year-old male without a history of other neoplasms. Histology showed papillary-cystic growth of predominantly oncocytic (Case 1) or mucinous (Case 2) cells surrounded by a p63-positive basal layer. The overall histology was reminiscent of oncocytic sinonasal papilloma (Case 1) and pancreatobiliary or salivary intraductal papillary mucinous neoplasms (Case 2). Ovarian-type stroma, invasion and malignant features were absent. Immunohistochemistry revealed expression of cytokeratin (CK) 7, but not carbonic anhydrase IX (CAIX) or paired box gene 8 (PAX8) (except for very focal PAX8 expression in Case 1). The TST15 gene panel and HRAS sequencing revealed no pathogenic mutations in BRAF, KRAS, EGFR, AKT1, or HRAS. The TruSight RNA fusion panel revealed an MKRN1-BRAF fusion in Case 1. No fusion was detected in Case 2. The three ELSTs showed classic features of the entity, expressed CK7, epithelial membrane antigen, PAX8, and CAIX, and lacked a basal cell layer. These novel cases suggest that papillary tumours of the ear represent a heterogeneous spectrum of distinct neoplasms unified by a prominent papillary-cystic pattern rather than a single entity. Future studies should clarify whether the MKRN1-BRAF fusion is a defining recurrent driver event, especially in those cases reported as sinonasal-type middle ear papillomas.

A Case Report of Hashimotos Thyroiditis

Background: Hashimoto?s thyroiditis is a common lifelong autoimmune disease of the thyroid gland. Case Presentation: A 63-year-old woman was clinically diagnosed as non toxic goiter. Thyroidectomy was done and specimen was sent for histopathological examination. A brownish and soft mass was received with size 6x5x4cm. Microscopic examination showed that proliferation of lymphoid follicles with germinal center of lymphoplasmacytic cells between acini. Some of acini were destroyed and atrophic, while some of them formed microfollicular structures. Acini were lined by simple cuboid epithelium with round oval nuclei, fine chromatin, and eosinophilic cytoplasm. Most of acini contained colloid inside lumen. Lying in between acini were found oncocytic cells with round nuclei, some with prominent nucleoli, fine chromatin, abundant and granular cytoplasm. Stroma consisted of fibrous connective tissue. Conclusion: Histopathological examination yielded the diagnosis of Hashimoto?s thyroiditis.

Clinical impact of follicular oncocytic (H\xfcrthle cell) carcinoma in comparison with corresponding classical follicular thyroid carcinoma

PurposeThere are controversial debates if patients with Hürthle cell carcinoma, also known as oxyphilic or oncocytic cell follicular thyroid carcinoma, have a poorer outcome. In this study, we systematically evaluated the clinical outcome in a large patient cohort following thyroidectomy and initial I-131 radioactive iodine therapy (RIT).MethodsWe retrospectively evaluated a total of 378 patients with diagnosed oncocytic follicular Hürthle cell carcinoma (OFTC) (N = 126) or with classical follicular thyroid carcinoma (FTC) (N = 252). Patients received thyroidectomy and complementary I-131 RIT. Clinical data regarding basic demographic characteristics, tumor grade, persistent disease and recurrence during follow-up, and disease-free, disease-specific, and overall survival were collected during follow-up of 6.9 years (interquartile range 3.7; 11.7 years). Univariate and multivariate analyses were used to identify factors associated with disease-related and overall survival.ResultsBefore and after matching for risk factors, recurrence was significantly more frequently diagnosed in OFTC patients during follow-up (17% vs. 8%; p value 0.037). Likewise, OFTC patients presented with a reduced mean disease-free survival of 17.9 years (95% CI 16.0–19.8) vs. 20.1 years (95% CI 19.0–21.1) in FTC patients (p value 0.027). Multivariate analysis revealed OFTC (HR 0.502; 95% CI 0.309–0.816) as the only independent prognostic factor for disease-free survival. Distant metastases of OFTC patients were significantly less iodine-avid (p value 0.014). Mean disease-specific and overall survival did not differ significantly (p value 0.671 and 0.687) during follow-up of median 6.9 years (3.7; 11.7 years).ConclusionsOur study suggests that recurrence is more often seen in OFTC patients. OFTC patients have a poorer prognosis for disease-free survival. Thus, OFTC and FTC behave differently and should be categorized separately. However, patients suffering from OFTC present with the same overall and disease-specific survival at the end of follow-up indifferent to FTC patients after initial RIT.

Causative role for defective expression of mitochondria-eating protein in accumulation of mitochondria in thyroid oncocytic cell tumors.

Oncocytic cell tumor of the thyroid is composed of large polygonal cells with eosinophilic cytoplasm that is rich in mitochondria. These tumors frequently have the mutations in mitochondrial DNA encoding the mitochondrial electron transport system complex I. However, the mechanism for accumulation of abnormal mitochondria is unknown. A noncanonical mitophagy system has recently been identified, and mitochondria‐eating protein (MIEAP) plays a key role in this system. We therefore hypothesized that accumulation of abnormal mitochondria could be attributed to defective MIEAP expression in these tumors. We first show that MIEAP was expressed in all the conventional thyroid follicular adenomas (FAs)/adenomatous goiters (AGs) but not in oncocytic FAs/AGs; its expression was defective not only in oncocytic thyroid cancers but also in the majority of conventional thyroid cancers. Expression of MIEAP was not correlated with methylation status of the 5′‐UTR of the gene. Our functional analysis showed that exogenously induced MIEAP, but not PARK2, reduced the amounts of abnormal mitochondria, as indicated by decreased reactive oxygen species levels, mitochondrial DNA / nuclear DNA ratios, and cytoplasmic acidification. Therefore, together with previous studies showing that impaired mitochondrial function triggers compensatory mitochondrial biogenesis that causes an increase in the amounts of mitochondria, we conclude that, in oncocytic cell tumors of the thyroid, increased abnormal mitochondria cannot be efficiently eliminated because of a loss of MIEAP expression, ie impaired MIEAP‐mediated noncanonical mitophagy.