Oncocytic Tumors Research Articles

Genetic validation of a TSC2 immunohistochemistry assay in TSC/mTOR-pathway altered renal tumors.

Pathogenic mutations in the genes associated with tuberous sclerosis complex (TSC)/mTOR pathway are linked to histologically diverse renal cell neoplasms, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and xanthomatous giant cell renal cell carcinoma (XGC RCC). Here, we validate a TSC2 immunohistochemistry (IHC) assay by comparison to genomic data in these neoplasms. Automated TSC2 IHC was performed on formalin-fixed paraffin embedded (FFPE) tissues from 38 genetically-confirmed TSC/mTOR-associated renal tumors (6ESCs, 16 EVTs, 13 LOTs, 2 XGC and 1 clear cell RCC) and visually scored in a semi-dichotomous fashion compared to internal control tissue. The positive predictive value (PPV) of TSC2 protein loss for underlying pathogenic mutation in TSC2 was 92% (11/12), while the negative predictive value (NPV) of intact TSC2 by IHC for lack of underlying pathogenic mutation in TSC2 was 81% (21/26). Intact TSC2 by IHC was 95% (21/22) specific for absence of underlying pathogenic TSC2 mutation. All the cases lacking TSC2 mutation with intact TSC2 protein had an underlying mutation in TSC1, MTOR or PIK3CA. Loss of TSC2 was 77% (10/13) sensitive for underlying TSC2 truncation mutations and 33% (1/3) sensitive for underlying TSC2 missense mutations. Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.

The Utility of BSND Immunohistochemistry in the Differential Diagnosis of Oncocytic and Warthin-like Mucoepidermoid Carcinoma of Salivary Gland.

BSND is a chloride channel subunit that is expressed in the normal salivary gland. We aimed to validate the utility of BSND immunohistochemistry in the differential diagnosis of oncocytic salivary gland neoplasms. BSND immunohistochemistry was performed in a retrospective cohort of 93 salivary gland lesions, enriched with tumors with oncocytic features and histologic variants of mucoepidermoid carcinoma (MEC). All oncocytomas (n = 18) showed diffuse membranous BSND immunopositivity. Warthin tumors (n = 18) were also positive for BSND, but the staining pattern was patchy cytoplasmic and membranous in 10-25% of tumor cells. Using a threshold of 10% BSND-positive cells, all Warthin tumors were positive, while none of Warthin-like MECs or non-MEC salivary tumors were positive. Applying the same 10% positivity criterion, two oncocytic MECs were positive for BSND. The percentage of BSND staining in oncocytic MECs was up to 20%. In contrast, BSND was diffusely positive in oncocytomas with a median percentage of positivity of 95% (range: 40 - 100%). Therefore, a higher threshold of > 20% BSND-positive cells may be considered when differentiating between oncocytoma and oncocytic MEC. BSND immunohistochemistry is a potentially useful diagnostic marker for salivary gland neoplasms, especially oncocytic and Warthin-like MECs. A threshold of ≥ 10% positivity can differentiate Warthin tumors from Warthin-like MECs, whereas > 20% positivity can be effective for separating oncocytomas from oncocytic MECs.

Sonography Could Predict Complete/Near-Complete Necrosis of Thyroid Tumors After Fine-Needle Biopsy: Necrotic Ring Sign.

Necrosis, a rare histologic alteration caused by the fine-needle aspiration biopsy (FNA) of thyroid tumors, could be problematic in the clinical management of such cases due to the difficulty in making a definitive histopathologic diagnosis. The aim of this study was to define US features that may help to predict FNA-induced necrosis which is more common in oncocytic tumors. This cross-sectional study consists of all patients who underwent thyroid surgery in our center between January 2011 and December 2023. All nodules, which complete/near-complete necrosis reported on final histopathology, were included into study when full video record of preoperative US exam also available for re-evaluation. US findings of necrotic tumors compared with control group consisting of similar histopathology without necrosis. A total of 11 patients have met the inclusion criteria during study period. Of these cases, seven were papillary thyroid carcinomas and four were follicular adenomas. Among the evaluated distinctive US features, necrotic ring offers the best accuracy (88%) and area under the curve (0.91) values in detecting necrosis after FNA and most valuable when combined with lack of intranodular vascularity. In the preoperative evaluation of surgical candidates, necrotic ring, refractive edge shadowing, posterior acoustic enhancement, and lack of vascular signal may predict complete/near-complete necrosis with great accuracy.

GATA3 Expression in Solid Vimentin-Negative Eosinophilic Renal Epithelial Tumors-A Comprehensive Study of 48 Tumors.

Vimentin-negative solid eosinophilic renal tumors, such as renal oncocytoma, chromophobe renal cell carcinoma (chromophobe RCC), low-grade oncocytic tumor (LOT) of the kidney, and eosinophilic vacuolated tumor (EVT), often present diagnostic challenge to pathologists as they can have significant morphologic overlap. Recent studies have shown that the LOT is consistently positive for GATA3. To test the utility of GATA3 in this potentially challenging diagnostic setting, we investigated GATA3 expression in 48 vimentin-negative solid eosinophilic renal tumors with unequivocal diagnosis, which included 19 LOTs, 3 EVTs, 12 chromophobe RCCs, 11 renal oncocytomas (ROs), and 3 FLCN-mutated renal tumors. GATA3 was at least focally positive in 89% of the LOTs (17/19), 67% of the EVTs (2/3), and 33% of the chromophobe RCCs (4/12) and was negative in all ROs (0/11) and FLCN-mutated renal tumors (0/3). Our study shows that GATA3 can be useful in differentiating between LOT and RO, but it can be focally positive in many tumors of EVT and chromophobe RCC. Therefore, GATA3 could be useful as a panel of immunohistochemical stains that are used in diagnostic algorithm of vimentin-negative solid eosinophilic renal tumors. However, one should not solely rely on GATA3 as vimentin-negative solid eosinophilic renal tumors can have overlapping GATA3 expression.

Reappraisal of Oncocytic Adenocarcinoma: Unveiling Its Connection to Oncocytic Variants of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma Through ImmunoHisto-Molecular Perspectives.

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.

Mitochondrial Proteome Defined Molecular Pathological Characteristics of Oncocytic Thyroid Tumors.

Oncocytic thyroid tumors are characterized by an elevated mitochondrial density within the cells, distinguishing them from other thyroid tumors, exhibit distinct clinical behaviors, including increased invasiveness and iodine therapy resistance. However, the proteomic alterations in oncocytic thyroid tumors remain inadequately characterized. In this study, we analyzed 156 Asian patients with oncocytic thyroid adenomas (OA) and carcinomas (OCA) to explore their clinical, genetic, and proteomic features. Genetic testing of 73 samples revealed frequent mutations in TERT, NRAS, EIF1AX, EZH1, and HRAS, with TERT promoter mutations being exclusive to OCAs. Proteomic analysis identified 66 mitochondrial-specific proteins significantly highly expressed in oncocytic tumors than in non-oncocytic tumors. This led to the development of a thyroid oncocytic score (TOS) to quantify oncocytic characteristics. Among these proteins, isocitrate dehydrogenase 2 (IDH2) was substantially overexpressed in oncocytic tumors and further confirmed by immunohistochemistry in oncocytic tumor slides (n = 41) and non-oncocytic tumor slides (n = 40). Moreover, IDH2 is significantly overexpressed in OCA compared to OA highlighting its potential as a biomarker for differential diagnosis of oncocytic tumors and malignancy. These findings improve the understanding of oncocytic thyroid tumors molecular pathology and suggest IDH2 as a valuable marker for clinical management.

Molecular Pathogenesis of Renal Neoplasms in Patients with Birt–Hogg–Dubé Syndrome

Birt–Hogg–Dubé syndrome (BHDS) is an autosomal dominant disease characterized by skin, lung, and renal manifestations. This syndrome is caused by a germline mutation in the FLCN gene, which leads to disruption in multiple downstream pathways. Renal cell carcinomas are one of the serious clinical manifestations of the disease, which usually presents as bilateral and multiple tumors. Morphologically, most of these tumors are classified as hybrid oncocytic tumors. Recent advances in molecular techniques have shed light on the pathogenesis of these renal tumors. In this review, we evaluate and summarize the current knowledge of BHDS, pathologic changes, and its molecular basis with the focus on the renal hybrid oncocytic tumor (HOT), their pathogenesis, and molecular underpinning.

Oncocytic Adrenal Neoplasms: Clinical Profiles and Long-Term Outcomes.

Background: Oncocytic adrenal neoplasms, defined by ≥90 % of oncocytic cells, are rare. The significance of oncocytic changes within an adrenal neoplasm remains unclear.Methods: A retrospective study of adults who underwent adrenalectomy at a large center identified pure oncocytic neoplasms on final pathology (1997-2022). Neoplasms were categorized based on Lin-Weiss-Bisceglia system as malignant, benign, or of uncertain malignant potential. Analysis was performed using Fisher exact, Kruskal-Wallis tests, and Kaplan-Meier analysis.Results: Among a total of 33 patients, 24% had benign, 36% malignant, and 39% neoplasm of uncertain malignant potential. None of the benign neoplasms recurred, while 50% of the malignant neoplasms recurred (median of 40 months). Two of 13 neoplasms initially thought to be of uncertain malignant potential recurred as distant metastatic adrenocortical carcinoma at 11 and 25 months, over a median follow-up duration of 31 months. Ki67% was available for 20 patients: median (IQR) Ki67% was 5 (1, 5) for benign, 10 (6, 15) for malignant, and 6.5 (5, 10) for neoplasms of uncertain behavior, P = 0.05. Recurred neoplasms had higher Ki67% at initial resection compared to cases that did not recur.Conclusion: While oncocytic adrenal neoplasms are rare, a significant proportion are malignant or have malignant potential. Judicious follow-up is required for oncocytic adrenal neoplasms of uncertain malignant potential, as they can recur as metastatic adrenocortical carcinoma. Ki67% should always be obtained in cases of malignancy or uncertain malignant potential as it can predict recurrence. Larger studies are needed to evaluate the appropriate follow-up protocols for these neoplasms.

Molecular Profiling and Surgical Outcomes in Indeterminate Thyroid Nodules: Experience from a Tertiary Care Center

Abstract Introduction/Objective This study examines molecular results(MR) and surgical follow-up(SFU) of cytologically- indeterminate thyroid nodules. Methods/Case Report Atypia-of-undetermined significance/suspicious-for-follicular-neoplasm cases that underwent Quest/ThyroSeq molecular testing between 2015-2022 were analyzed for MR, SFU and lymph node metastasis(LNM). Results (if a Case Study enter NA) 417 cases(Quest=192, ThyroSeq=225). 59% had SFU. 43% malignancy rate.SFU for Quest(49%): non-neoplastic(NNP)=20%, neoplastic(NP)=80%. MR in these cases:NRAS=48, HRAS=19, BRAF=15, KRAS=8, RET/PTC=3, PAX8=2. SFU: papillary thyroid carcinoma(PTC)=35, non-invasive-follicular-thyroid- papillary-neoplasm with papillary-like nuclear features(NIFTP)=20, thyroid nodular follicular disease(TFND)=18, follicular adenoma(FA)=10, follicular carcinoma(FC)=5, oncocytic carcinoma(OC)=1, lymphocytic thyroiditis(LT)=1. Surgical-molecular correlation(SMC): PTC in 3/3 RET/PTC-mutated, 14/15 BRAF-mutated cases. 1 TFND was BRAF- positive. RAS-mutated category: NIFTP=20,PTC=18,TFND=17,FA=9, OA=5, FC=5, LT=1. In RAS-mutated PTCs, NRAS was most common(n=13), followed by HRAS(n=4) and KRAS(n=1). 2 PAX8-mutated cases showed FA and OC. 9/41 malignant cases, all PTC, had LNM, MR:BRAF=6, HRAS=2, RET/PTC=1.SFU for ThyroSeq(68%): NN=10%, NNP=90%. MR:NRAS=34, copy number alterations(CNAs)=25, HRAS=14, BRAF=13, KRAS=11, gene expression alterations(GEA)=7, THADA+IGF2BP3=7, CNAs Hurthle cell type(HCT)=6, EIF1AX=6, DICER1=4, PAX8- PPARG fusion=4, CNAs+GEA=3, NTRK3=3, TERT=2, RAS+EIF1AX=2, TERT+CNAs=2, EIF1AX=1, EZH1=1, RET/PTC1 fusion=1, ALK=1, BRAF K601E=1,RAS+TERT=1, RAS+TERT+PTEN+EIF1AX=1, TERT+BRAF=1, TERT+EIF1AX=1,TP53+CNAs=1. SFU:PTC=39, NIFTP=31, OA=21, FA=20, papillary microcarcinoma(PMiC)=13, TFND=10, OC=7, LT=6, FC=5, poorly differentiated carcinoma(PdC)=1.10/13 BRAF-mutated cases were PTC, other 3 PMiC. SFU of RAS-mutated cases(n=59):TFND=6, LT=4, NIFTP=19, FA=8, OA=4, PTC=13, PMiC=2, FC=2. RAS mutations in PTC: KRAS=6, HRAS=4, NRAS=3. SFU of CNAs-HCT: OA=3, OC=2, TFND=1. Infrequently detected mutations with SFU of PTC:RET/PTC(1/1), ALK(1/1), RAS+TERT(1/1), TERT+BRAF(1/1), BRAF K601E(1/1), RAS+EIF1AX(1/2). SFU of RAS+TERT+PTEN+EIF1AX:PdC. 11/65 malignant cases, all PTC had LNM:BRAF=5, KRAS=3, CNAs=1, EIF1AX=1, TERT+BRAF=1. Conclusion Substantial proportion of cases with positive MR underwent surgical resection. BRAF-positive and CNAs- HCT correlated with PTC and oncocytic neoplasms, respectively. BRAF-positive PTCs had a higher incidence of LNM compared to wild-type cases(46% vs.18%).

A Case Series of a Rare Parotid Gland Oncocytic Mucoepidermoid Carcinoma

Abstract Introduction/Objective We analyzed two cases of oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland which highlight the diagnostic challenges of oncocytic salivary gland neoplasms. OMEC’s are a rare type of salivary gland tumor commonly arising from the parotid gland that can easily be mistaken as benign. Proper pathologic diagnosis of these masses is critical, as it guides therapeutic intervention and has prognostic significance. Methods/Case Report In this case series, two patients were analyzed retrospectively for unilateral parotid masses. Results (if a Case Study enter NA) In a 67-year-old female, an MRI and biopsy were performed. Only a differential diagnosis could be provided, which favored oncocytoma or oncocytic carcinoma. Due to this uncertainty, a complete excision of the mass was performed. Considering the cytomorphology, immunohistochemistry (CK5/6 and P63 in oncocytes), and mucicarmine special stain highlighting scattered mucocytes, the patient was diagnosed with a low- grade OMEC. In our second case, an 80-year-old female, FNA of a posterior left ear mass 1 year prior revealed a low- grade oncocytic proliferation. With the presence of a left parotid mass one year later, additional imaging was performed and showed increased T2 hyperintensity on MRI, which caused concern for the clinicians. A superficial limited parotidectomy was performed and a differential of oncocytoma versus oncocytic variant of mucoepidermoid carcinoma was rendered. Further tumor characterization with fluorescence in situ hybridization (FISH) demonstrated a MAML2 translocation which guided diagnosis of OMEC. Conclusion With approximately 30% of all malignant salivary gland tumors being constituted by mucoepidermoid carcinoma, the ability to accurately diagnose even this rare subtype, oncocytic mucoepidermoid carcinoma, is of significant importance and relevance to pathologists in many practice settings. Herein we demonstrate the utility of H&E morphology, immunohistochemistry, and MAML2 FISH in diagnosing OMEC in the setting of oncocytic salivary gland lesions. Future avenues, including tumor molecular profiling, will aid in elucidating clinicopathologic characteristics of this entity.

7040 Embolization Of Hepatic Metastases Is Effective For Palliative Management Of Severe Cushing Syndrome

Abstract Disclosure: S. Zhang: None. C. Musonza: None. A. Pillai: None. M. Ramos-Roman: None. J. Abramowitz: None. S. Mirfakhraee: None. P. Polanco: None. A.P. Dackiw: None. S. Al Mutar: None. A. Mallik: None. L. Jia: None. O. Hamidi: None. Background: Cushing syndrome (CS) due to metastatic endocrine neoplasms poses substantial treatment challenges. Arterial embolization and Yttrium-90 (Y-90) radioembolization for hepatic metastases are effective in the management of metastases due to neuroendocrine tumors (NETs). However, data are scarce on the role of embolization of liver metastases in patients with CS. Here, we report two cases of severe CS due to bulky hepatic metastases treated with embolization techniques. Case 1 A 49-year-old woman presented with severe ectopic CS and a 15-cm hepatic metastatic conglomerate. Liver biopsy showed NET of unknown primary. Treatment with subcutaneous octreotide and metyrapone (total daily dose 3000mg) resulted in modest improvement of serum cortisol from 89.8 to 45.8 mcg/dL. She was not a candidate for bilateral adrenalectomy or hepatectomy due to bulky hepatic metastases and subsequently underwent bland embolization to the hepatic conglomerate. Cortisol decreased from 63.9 mcg/dL to 13.8 mcg/dL after the initial procedure, but then rebounded to 35.8 mcg/dL. Serum cortisol decreased to 19.4 mcg/dL following additional embolization, and she was discharged on metyrapone 500mg three times daily. CS remained controlled 12 weeks after the procedure. Interval imaging showed a decrease in size of the dominant hepatic mass (9.7 cm). The patient is currently undergoing chemotherapy with carboplatin and etoposide. Case 2: A 40-year-old man presented to an outside institution with CS due to a 6.9 cm right adrenal mass and underwent adrenalectomy. Pathology showed oncocytic neoplasm of uncertain malignant potential. A year later, he presented to our hospital with recurrent CS and was found to have a 10.2 cm liver lesion, confirming stage IV adrenocortical carcinoma. FDG PET/CT did not show additional lesions. He was treated with osilodrostat and mitotane but his hypercortisolism remained uncontrolled. Mitotane was discontinued after a few doses due to side effects. Metastasectomy was attempted but halted due to extensive peritoneal carcinomatosis noted in the operating room. He was subsequently treated with Y-90 radioembolization to the liver metastasis. Afterwards, osilodrostat was held and serum cortisol decreased from 49.6 to 6.9 mcg/dL on day 14 post-procedure. Hydrocortisone was initiated for treatment of adrenal insufficiency. He received cisplatin, doxorubicin, and etoposide, but stopped after the first cycle due to side effects. Recent imaging showed a decrease in the hepatic lesion to 6.5 cm. Presently, the patient continues to have persistent adrenal insufficiency confirming remission of CS. Conclusion: These cases illustrate the potential efficacy of bland embolization and Y-90 radioembolization for palliative treatment of severe CS in patients with hepatic metastases. Presentation: 6/2/2024

7387 A Rare Case Of Concomitant Intrathyroidal Parathyroid Carcinoma With Osteitis Fibrosa Cystica, Masquerading As Oncocytic Thyroid Carcinoma - A Post-operative Diagnosis

Abstract Disclosure: Y. Koh: None. D.E. Chew: None. T.P. Quek: None. Introduction: Parathyroid carcinoma is a rare form of malignancy. An intrathyroidal location of parathyroid carcinoma further complicates the diagnosis as it may be mistakenly presumed to be of thyroid origin instead. We present a case report of an intrathyroidal parathyroid carcinoma which was diagnosed post-total thyroidectomy. Clinical case: A 72-year-old lady was found to have an intrathyroidal mass after presenting with unintentional weight loss and chronic constipation. Ultrasound of the neck showed a 4.0 x 2.9cm markedly hypoechoic solid mass in the mid-lower right thyroid lobe. Fine needle aspiration of the mass was suspicious for an oncocytic neoplasm. She underwent total thyroidectomy with central neck dissection for concerns of oncocytic thyroid carcinoma. Intraoperatively, a 4cm right hard intrathyroidal nodule invading into the right recurrent laryngeal nerve was observed. All 4 parathyroids were identified and preserved. Post-operatively, routine biochemistry to monitor for hypocalcemia showed hypercalcemia instead. This quickly transitioned into hypocalcemia on post-operative day 4, with biochemistry supportive of hungry bone syndrome [adjusted calcium 2.05mmol/L [normal range (NR) 2.15-2.5], phosphate 0.6mmol/L (NR 0.8-1.4), PTH 8.2pmol/L (NR 0.8-6.8), 25-OH vitamin D 18ug/L (NR 30-100)]. She was started on oral calcium carbonate, calcitriol and cholecalciferol aiming for normocalcemia. Evidence for underlying primary hyperparathyroidism were sought for, which showed osteitis fibrosa cystica, severe osteoporosis and an ossifying fibroma of the mandible, suggesting underlying hyperparathyroidism-jaw tumour-syndrome. The intra-operative histology was reported as oncocytic carcinoma with angio- and perineural invasion, presumed to be thyroid in origin. Given our suspicion of underlying primary hyperparathyroidism, we requested our pathology colleagues to perform additional immunochemical stains, which stained diffusely positive for parathyroid hormone, GATA3 but were negative for thyroglobulin, thyroid transcriptor factor-1, confirming its parathyroid origin. Her hungry bone syndrome resolved 22 weeks post-operatively. Till present (14 months post-operatively), her calcium and PTH levels remain normal and ultrasound of the neck did not reveal any evidence of recurrence. She declined genetic screening. Clinical Lesson: A high index of suspicion is required for the diagnosis of parathyroid carcinoma. In a patient who presents with constitutional symptoms and a neck mass, it is imperative to consider parathyroid disease as a differential diagnosis. A lesion with oncocytic morphology may be of parathyroid or thyroid origin, and the use of immunochemical stains can help differentiate them. Effective communication between clinicians and pathologists is essential in clinching the correct cytopathological diagnosis. Presentation: 6/3/2024

8214 Adrenocortical Oncocytic Neoplasm Presenting As Cushing's Syndrome: A Case Report

8214 Adrenocortical Oncocytic Neoplasm Presenting As Cushing's Syndrome: A Case Report

A Confirmed Extrarenal Birt-Hogg-Dubé-Associated Oncocytic Neoplasm.

Birt-Hogg-Dubé (BHD) syndrome is a rare inherited disease characterized by a variety of renal epithelial tumors and oncocytosis, with extrarenal manifestations primarily consisting of pulmonary cysts and cutaneous fibrofolliculomas. Here we report a unique case of a primary extrarenal BHD-associated oncocytic epithelial neoplasm which arose between the duodenum and head of the pancreas. The unusual morphology and immunoprofile of this lesion defied classification as any previously reported entity, despite an extensive diagnostic workup. The immunohistochemical and molecular features indicate the tumor was driven by FLCN loss, and thus a consequence of the underlying germline mutation with a somatic second hit. This tumor is the first reported example of an extrarenal BHD-associated oncocytic epithelial tumor driven by FLCN loss.

Unilateral gynecomastia unveiling an adrenal finding: a case report of a large adrenal oncocytic tumour

Unilateral gynecomastia unveiling an adrenal finding: a case report of a large adrenal oncocytic tumour

Imaging of Chromophobe Renal Cell Carcinoma with 99mTc-Sestamibi SPECT/CT: Considerations Regarding Risk Stratification and Histologic Reclassification.

Indeterminate renal masses are increasingly incidentally found on cross-sectional imaging. 99mTc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) scans can be used to identify oncocytomas and oncocytic renal neoplasms, including a subset of chromophobe renal cell carcinomas (chRCCs), which are viewed as false-positive. Patients imaged with renal sestamibi scans between 2014 and 2023 were reviewed. Those patients with solitary tumors that were originally classified as chRCC were included in the analysis. Imaging with SPECT/CT from the liver dome down had been carried out 75min after the administration of 925MBq of 99mTc-sestamibi. All available H&E and immunostained slides were re-reviewed and classified according to WHO 2022 criteria. Confirmatory immunohistochemical stains were performed in tumors considered morphologically suspicious for non-chRCC entities. A total of 18 patients with solitary tumors were included in the final analysis. 13/18 (72.2%) tumors in this cohort remained classified as chRCC, with 4/18 (22.2%) being eosinophilic-variant chRCC. The reclassified tumors (5/18 [27.8%]) included 2/18 (11.1%) low-grade oncocytic tumor (LOT), 1/18 (5.5%) eosinophilic vacuolated tumor (EVT), and 2/18 (11.1%) unclassified low-grade oncocytic neoplasms. As such, only 2/9 (22.2%) qualitatively "hot" tumors were chRCC other than eosinophilic-variant and only 1/9 (11.1%) "cold" tumors was a histology other than chRCC. Based on current histopathologic classification methods, it is likely that the "false-positive" rate of uptake on renal sestamibi scans with chRCC has been over-stated. Further study is warranted to better refine the optimal utility of renal sestamibi scans for non-invasive risk stratification of indeterminate renal masses.

Low-grade oncocytic tumor of the kidney: imaging features of a novel tumor entity.

Low-grade oncocytic tumor (LOT) is a rare renal tumor that has emerged from the spectrum of eosinophilic/oncocytic renal tumors and poses a diagnostic challenge due to its similarity to chromophobe renal cell carcinoma (CHRCC) and renal oncocytoma (RO). The imaging features of this novel tumor entity have not yet been clearly described. The purpose of this study was to describe the imaging features of LOT with radiologic-pathologic correlation. We conducted a retrospective observational study involving two expert centers. We identified 12 pathologically proven LOT with preoperative imaging available, including at least computed tomography (CT) or magnetic resonance imaging (MRI), from the past 12 years. Three experienced radiologists performed the imaging analysis independently. All tumors presented well-defined borders. Nine of the 12 LOT exhibited an early peripheral enhancement with complete or almost complete centripetal fill-in on nephrographic or delayed phases without any particular shape. Three showed a homogeneous contrast enhancement. Macroscopic fat and calcifications were not observed in any of the tumors. Early peripheral enhancement with complete or almost complete centripetal fill-in on nephrographic or delayed phases without any particular shape suggests a LOT diagnosis. Further analyses involving larger studies are needed to fully confirm these imaging characteristics. To date, a percutaneous biopsy should be performed before considering management.

Frequency and clinicopathologic features of renal low-grade oncocytic tumour and eosinophilic vacuolated tumour: reclassification of 605 eosinophilic tumours including patients managed with active surveillance

AimsLow-grade oncocytic tumour (LOT) and eosinophilic vacuolated tumour (EVT) are recently described emerging entities, which demonstrate distinct features but are not yet recognised as separate neoplasms in the fifth WHO...

Invasive intraductal oncocytic papillary neoplasms (IOPN) and adenocarcimoma arising from intraductal papillary mucinous neoplasms (A-IPMN) of the pancreas: comparative analysis of clinicopathological features, patterns of recurrence and survival: a multicentre study

BackgroundIntraductal oncocytic papillary neoplasms (IOPNs) of the pancreas are now considered a separate entity to intraductal papillary mucinous neoplasms (IPMN). Invasive IOPNs are extremely rare, and their recurrence patterns, response to adjuvant chemotherapy and long-term survival outcomes are unknown. MethodsConsecutive patients undergoing pancreatic resection (2010–2020) for invasive IOPNs or adenocarcinoma arising from IPMN (A-IPMN) from 18 academic pancreatic centers worldwide were included. Outcomes of invasive IOPNs were compared with A-IPMN invasive subtypes (ductal and colloid A-IPMN). Results415 patients were included: 20 invasive IOPN, 331 ductal A-IPMN and 64 colloid A-IPMN. After a median follow-up of 6-years, 45% and 60% of invasive IOPNs had developed recurrence and died, respectively. There was no significant difference in recurrence or overall survival between invasive IOPN and ductal A-IPMN. Overall survival of invasive IOPNs was inferior to colloid A-IPMNs (median time of survival 24.4 months vs. 86.7, months, p = 0.013), but the difference in recurrence only showed borderline significance (median time to recurrence, 22.5 months vs. 78.5 months, p = 0.132). Adjuvant chemotherapy, after accounting for high-risk features, did not reduce rates of recurrence in invasive IOPN (p = 0.443), ductal carcinoma (p = 0.192) or colloid carcinoma (p = 0.574). ConclusionsInvasive IOPNs should be considered an aggressive cancer with a recurrence rate and prognosis consistent with ductal type A-IPMN.

Oncocytic/Hürthle cell lesions have the same implied risk of neoplasm/malignancy as their follicular counterparts.

There are conflicting results on whether the presence of oncocytes modifies the risk of neoplasm (RON) or malignancy (ROM) for thyroid fine-needle aspirates (FNAs): Atypia of undetermined significance AUS and Follicular Neoplasm, FN, or Oncocytic Neoplasm, ON. To our knowledge, the effect of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has not yet been studied. We compared RON and ROM between follicular type AUS (AUS-FT) and oncocytic type AUS (AUS-OT) and between FN and ON. We retrospectively analysed all thyroid FNAs with the diagnostic category of AUS-other or Neoplasm (2005-2015). AUS-FT had predominance of microfollicles and AUS-OT had predominance of oncocytes. Histology follow-up was then reviewed and RON, ROM was then calculated and compared (significant at p < 0.05). We repeated the search for 2018 to evaluate for NIFTP effect. Pre-NIFTP, 859/5063 cases (17%) were AUS-FT, AUS-OT, FN, and ON. Histology follow-up was available for 297 cases (35%). RON was 83/183 (45%) for AUS-FT, 35/76 (46%) for AUS-OT, 15/25 (60%) for FN and 11/13 (85%) for ON. Post-NIFTP, RON was 11/31 (35%) for AUS-FT, 5/8 (63%) for AUS-OT, 1/2 (50%) for FN and 4/5 (80%) for ON. For both periods, RON, ROM of AUS-FT was not significantly different than AUS-OT, and no significant differences were observed comparing FN and ON. The predominance of oncocytes does not modify the implied RON, ROM for categories of AUS or FN\ON, even after the adoption of NIFTP.