Over the past several decades, rapid advances in molecular genomics have transformed our understanding of thyroid malignancies and are increasingly integrated into international clinical guidelines. Mutational profiles and epigenetic events are now recognized not only as diagnostic and prognostic tools but also as predictors of therapeutic response. Papillary, follicular, oncocytic, medullary, and anaplastic thyroid carcinomas harbor distinct early driver mutations, such as BRAFV600E, RAS, and fusion events (RET, NTRK, and ALK), that cooperate with secondary alterations (TERT promoter, TP53, PIK3CA, and CDKN2A/B loss) to drive dedifferentiation, metastasis, and therapeutic resistance. Insights from The Cancer Genome Atlas (TCGA) and transcriptomic scoring systems (e.g., BRAF–RAS score) now link genotype to tumor morphology, metastatic tropism, and radioactive iodine refractoriness. These molecular insights have been incorporated into updated risk stratification frameworks, preoperative surgical planning, and treatment algorithms, informing the selection of kinase inhibitors, redifferentiation strategies, and enrollment in genotype-directed clinical trials for radioiodine-refractory disease. This review synthesizes recent evidence connecting genomic alterations to clinical behavior and highlights their translation into evolving approaches for thyroid cancer management.

A retrospective analysis of clinicopathological features was conducted on 10 cases of thyroid tumors with PTEN mutations from Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Fujian Provincial Hospital, and the Affiliated Hospital of Qingdao University from 2020 to 2024. Histomorphological features were quantified using the Thyroid Histomorphological PTEN Hamartoma Syndrome (PHTS) scoring system(THiPS), immunophenotypic profiling and genetic features were examined via immunohistochemical staining and next-generation sequencing respectively. The cohort included 3 males and 7 females, with the age [M(Q1,Q3)] of 68.0(53.0, 74.0) years. Those 10 cases included papillary thyroid carcinomas (3 cases), oncocytic carcinoma of the thyroid (2 cases), follicular thyroid carcinoma (1 case), differentiated high-grade thyroid carcinoma (1 case), and thyroid low risk neoplasm (3 cases). The cases in this study had low THiPS scores [(1.0±1.15) scores], and all lacked the characteristic morphological features of PHTS. Immunohistochemical staining showed that loss of PTEN expression was confirmed in 7 cases, positive expression was found in 3 cases with non-sense PTEN mutation. Molecular analysis revealed co-mutations with PTEN in 80% of cases (8/10), including BRAFV600E(3 cases), TERT promoter (4 cases), and TP53 mutations (2 cases), while 2 cases harbored PTEN-only mutations. Follow-up data were obtained for 6 cases, with a follow-up period of 15.0 (9.0, 20.0) months. Among them, 1 case was initially diagnosed with OCT pulmonary metastasis, while the remaining 5 cases showed no recurrence or metastatic lesions during the follow-up period. The THiPS score has limited diagnostic value for thyroid tumors with PTEN alteration. Negative PTEN immunohistochemical staining may suggest a PTEN mutation, but positive staining does not exclude a genetic alteration. PTEN gene mutations can be combined with BRAF, TERT, and TP53 alteration.

Introduction: Oncocytic adrenocortical carcinoma (OAC) is a rare histologic variant of adrenocortical carcinoma. It is characterized by cells with abundant eosinophilic cytoplasm because of high mitochondrial content. Unlike conventional Adrenocortical carcinoma (ACC), which is typically aggressive, OAC often presents with a more indolent biological behavior. The paradoxical features of OAC make the diagnosis and management challenging. Case Report: A 45-year-old female presented with weight loss and left-sided abdominal pain, with initial imaging revealing a large (24 cm) left adrenal mass. Imaging revealed that the mass had radiologic signs and necrotic features concerning for malignancy. She subsequently underwent a left adrenalectomy with en bloc pancreatectomy, splenectomy, and left nephrectomy along with paraaortic lymphadenectomy. Histopathology revealed classic oncocytic morphology with low Ki-67 index (2%) and absence of any lymph node involvement, despite venous and capsular invasion. Due to the venous invasion alone, the tumor met the Lin–Weiss–Bisceglia (LWB) criteria for malignancy. Additional molecular analysis revealed a favorable diagnosis by showing TP53 alterations, low tumor burden, along with microsatellite stability. Postoperatively, the patient recovered and was administered external beam radiation. Conclusion: This case is an example of a rare subtype of ACC and highlights a clinical paradox. In patients with OAC, a large tumor size with necrosis may not always be associated with a poor prognosis. Additionally, OAC has unique diagnostic and management challenges due to its rare nature. However, surgery is still the mainstay treatment for OAC, with the role of mitotane in adjuvant therapy still being explored.

Adrenal cortical carcinoma (ACC) is a rare malignancy, and oncocytic ACC (OAC) is a rare histopathologic variant of ACC, with <70 cases documented worldwide as of 2021. This is a case of a 64-year-old female initially presenting with epigastric-to-periumbilical pain, left flank pain, nausea, vomiting, and bloatedness. Computed tomography (CT) urogram revealed a 12.2 x 12.7 x 15 cm left adrenal mass, with pulmonary metastases on chest CT. The patient was clinically and biochemically unremarkable based on the hormonal panel. Left thoracoabdominal adrenalectomy was done, and the left adrenal mass was identified as a high-grade non-functioning OAC on histopathology and immunohistochemistry. The patient showed clinical improvement on chemotherapy with etoposide, cisplatin, doxorubicin (EDP), without mitotane, due to local unavailability. In conclusion, while EDP + mitotane is the standard therapy for metastatic cases, EDP alone showed promising outcomes in improving quality of life and resolving paraneoplastic neuropathy in the absence of mitotane. To date and to the best of our knowledge, this is the first documented case of non-functioning OAC in the Philippines. DS-related Kaposi sarcoma (KS) progresses rapidly with early mucosal and systemic involvement. Early diagnosis and treatment are crucial as they significantly impact the outcome. This is a case of disseminated cutaneous and gastrointestinal KS in a 24-year-old Filipino male living with HIV, presenting with hyperpigmented violaceous subcutaneous nodules, odynophagia, progressive dysphagia, and symptomatic anemia. Capsule endoscopy demonstrated utility in diagnosing gastrointestinal KS lesions, highlighting its crucial role when conventional upper endoscopy was challenging due to oropharyngeal involvement. Diagnostic limitations, mainly the unavailability of human herpesvirus-8 (HHV-8) immunohistochemical stain, were addressed through high clinical suspicion. Multidisciplinary approach including chemotherapy with liposomal doxorubicin, radiotherapy, and supportive care eventually yielded good clinical response. This case emphasizes the importance of early diagnosis, timely intervention, and long-term surveillance in achieving favorable outcomes for patients with KS despite some diagnostic limitations. Keywords. Oncocytic, Adrenal cortical carcinoma, Abdominal pain, Non-functioning, Case report

Oncocytic (Hürthle cell) carcinoma of the thyroid (OCT) is characterized by widespread loss of heterozygosity (LOH), mitochondrial accumulation and recurrent mitochondrial DNA mutations leading to impairment of complex I. Here, we establish and characterize a novel OCT cell line, UT946, which displays severe mitochondrial electron transport chain dysfunction and a Warburg metabolic phenotype. Using a series of cytoplasmic hybrids, we establish that the complex I defect in UT946 stems from a nuclear-encoded loss of function mutation in the complex I subunit NDUFS1. To our surprise, the mutation in NDUFS1 was inherited as a recessive germline allele that underwent LOH in the tumor to expose functional loss of complex I. A re-analysis of 91 OCT tumor genomes revealed that LOH-driven exposure of recessive germline mutations in complex I subunits was a recurrent mechanism underlying complex I inactivation in OCT. These findings unveil a new germline-driven mechanism of complex I loss and metabolic reprogramming in cancer, and provide further evidence of the strong selective pressure for complex I impairment in OCT.

Vascular Flip-Flop: Theranostic Transition in Oncocytic Thyroid Carcinoma

High-resolution imaging has increased the detection rate of adrenal gland neoplasms, necessitating changes in the management of patients with adrenal incidentalomas. Despite existing guidelines, the treatment strategy in patients with incidental adrenal gland neoplasms of 4 cm remains debatable. According to the updated EHS/ENSAT guidelines on incidentalomas (2023), benign neoplasms with ≤10 HU do not require further imaging examinations. For neoplasms of 4 cm with a native density of 11–20 HU, a follow-up examination after 12 months is recommended. This paper presents a clinical case of adrenocortical cancer with autonomous cortisol secretion, which originated from a nonfunctioning right adrenal gland neoplasm of 2 cm. The tumor was detected accidentally during abdominal and retroperitoneal ultrasound and computed tomography; however, malignant transformation did not occur until 11 years later. A comprehensive preoperative assessment, including biochemical and imaging examinations, confirmed that the patient was eligible for elective surgery. A pathological examination confirmed an oncocytic adrenocortical carcinoma (Ki-67: 40%).

Follicular thyroid carcinoma (FTC) and oncocytic thyroid carcinoma (OTC) are distinct entities with differing biological behaviors, yet optimal surgical and radioactive iodine (RAI) therapy management remains debated. Demographic, clinicopathological, and treatment characteristics were gathered from the Surveillance, Epidemiology, and End Results (SEER) database and compared between FTC and OTC according to tumor size. The Kaplan-Meier method and log-rank test were used to analyze cancer-specific survival (CSS). The effect of potential predictors associated with survival was estimated using the Cox regression model. 13,653 patients were included in our study. OTC patients were older and presented higher rates of extrathyroidal extension (ETE) and lymph node metastases (LNM), while FTC had higher distant metastasis (DM) rates. Increasing tumor size was correlated with worse features in both subtypes. Total thyroidectomy (TT) had no CSS benefit over less than TT (LTT) for FTC ≤2 cm or any OTC size group. TT was paradoxically associated with worse CSS for FTC >2 cm. RAI therapy did not improve CSS for patients with ETE (FTC or OTC) or DM (OTC). Multivariable analysis confirmed that TT was independently associated with worse CSS in FTC but not in OTC, while RAI therapy was beneficial in FTC but not in OTC. FTC and OTC exhibited distinct clinical behaviors. In conclusion, TT did not improve CSS for small FTC (≤2 cm) or any OTC, and appeared to be associated with worse outcomes in larger FTC. RAI therapy provided limited benefit in OTC, especially with DM. Treatment should be individualized, avoiding routine aggressive surgery or RAI.

Pediatric adrenocortical carcinoma (ACC) is rare malignancy, and its oncocytic variant is exceptionally rare in infants. A 1-year-old girl presented with excessive hair growth and hoarseness of voice for 8 months of age. Investigations revealed elevated androgen levels, and whole-body 18F FDG PET-CT imaging showed an isolated large left adrenal mass. The mass was surgically excised, and histopathology confirmed oncocytic adrenocortical carcinoma with a Wieneke score of 5, indicating malignancy. The postoperative course was uneventful with stabilization on antihypertensive and corticosteroid therapy.

Introduction: Oncocytic cell tumours (OCTs), previously referred to as Hürthle cell tumours of the thyroid, are a subset of thyroid and endocrine neoplasms that pose diagnostic and therapeutic challenges owing to their unpredictable clinical behaviour. The transcriptomic and proteomic landscapes of OCTs remain poorly characterized compared with those of mitochondrion-rich neoplasms (MRNs: thyroid tumours with ≥75% oncocytic cells that share similar morphology but harbour nuclear driver mutations consistent with their respective histotypes rather than mitochondrial alterations). Methods: We performed RNA and protein sequencing on 12 OCT samples and 6 MRNs. This study was prompted by the understanding that oncocytic morphology alone does not necessarily predict tumour behaviour. Results: RNA sequencing analysis identified 47 downregulated and 38 upregulated differentially expressed genes (DEGs) in OCTs relative to MRNs, with significant enrichment in pathways related to heme metabolism. Protein sequencing further revealed 20 under-expressed and 64 over-expressed differentially expressed proteins (DEPs) in OCTs. Notably, all oncocytic carcinomas formed a distinct cluster separate from the MRNs, indicating a unique proteomic profile. Conclusion: Most of the DEPs were involved in three key cellular pathways: epigenetic regulation, the tumour microenvironment, and protein biogenesis, suggesting that these processes may underlie the distinctive morphology and behaviour of OCTs. These findings highlight the need for continued research into these molecular mechanisms to improve the diagnostic accuracy and develop targeted therapies for patients with OCTs.

Disclosure: M.R. Graff: None. A. Fingeret: None. O. Shats: None. C. Zheng: None. B. Swanson: None. W.S. Goldner: None. A. Kotwal: None. Background: Differentiated thyroid carcinoma (DTC), specifically papillary thyroid cancer (PTC), is the leading endocrine malignancy. BRAFV600E is the most common driver mutation in PTC and is present in approximately 60% of cases overall. Recent studies suggest using this with histologic data to predict risk of recurrence could be synergistic. The gold standard for detecting BRAFV600E in DTC has been NextGen sequencing. Efforts have been made to screen the tumors first with immunohistochemistry (IHC), which is quick, inexpensive, and easily implemented compared to its counterpart, and this method was used for data collection in this study. Methods: We obtained paraffin embedded DTC tissue, created Tissue microarrays, then performed IHC for BRAFV600E mutation. BRAFV600E expression was calculated using an H-score: the staining intensity (0-3) multiplied by the amount of tumor that stained positive. H-score >0 was considered positive for BRAFV600E. Clinicopathologic features including extrathyroidal extension, angiolymphatic invasion (ALI), lymph node (LN) ratio (number of positive LN/total LN removed), tumor size, AJCC stage, response to therapy, and structural recurrence were evaluated for association with BRAFV600E mutation. To compare the distribution of variables between positive and non-positive H score groups, Chi-square test, t-test, and log-rank test were used for categorical, continuous, and time-to-event variables, respectively. Results: We evaluated 234 DTC specimens with IHC. BRAFV600E mutation was detected in 109 (66%) of the 166 PTC, 21(41%) of 51 follicular variant PTC, 1 (100%) of 1 tall cell variant of PTC, 2 (18%) of 11 FTC, and 1 (20%) of 5 oncocytic carcinoma specimens. Factors including LN ratio [0.21 (SD=0.32) vs 0.12 (SD=0.26), p=0.002], number of LN removed [10.56 (SD=17.2) vs 5.02 (SD=9.85), p<0.001], and presence of ALI (p=0.015) were significantly associated with BRAFV600E mutation. When stratified by age, the association of BRAFV600E with LN ratio was not significant in age <55 years but remained significant in age ≥ 55 years. In the age ≥ 55 years group, BRAFV600E was significantly associated with the presence of Hashimoto’s thyroiditis (p=0.02). BRAFV600E was not significantly associated with AJCC stage, ATA risk category, response to therapy, structural recurrence, and overall survival. Conclusions: The high frequency of BRAFV600E mutation detected in PTC and its association with LN ratio demonstrate that IHC is a reliable tool for detecting BRAFV600E in DTC. This strengthens the feasibility of using IHC for rapid results when necessary to complement or replace NextGen sequencing. In this cohort of DTC, BRAFV600E was associated with histopathological aggressiveness but did not translate to differences in response to therapy or survival, supporting the need for incorporating other clinicopathological and molecular factors. Presentation: Saturday, July 12, 2025

Synchronous Papillary and Oncocytic Thyroid Carcinomas: An Unusual Occurrence

Malignant struma ovarii (MSO) represents a rare form of ovarian tumor, necessitating further refinement in both classification systems and management approaches. In this study, we aimed to delineate the clinicopathological and molecular characteristics of MSO while assessing the utility of the World Health Organization (WHO) 2022 thyroid tumor classification framework for its diagnostic subtyping and clinical management. We analyzed MSO cases through comprehensive histopathology, immunohistochemistry (IHC), and targeted next-generation sequencing (NGS). The nine MSO cases comprised three papillary thyroid carcinomas (PTC; one follicular variant), four follicular thyroid carcinomas (FTC), one oncocytic (Hürthle cell) carcinoma (OCA), and one differentiated high-grade thyroid carcinoma (DHGTC). All tumors were unilateral and FIGO stage I. The patients (median age 59, range 23-73years) most often presented with an adnexal mass or abdominal pain. Histologically, all cases showed thyroid-type carcinoma arising within a teratomatous ovary. IHC demonstrated universal thyroid differentiation (TTF-1, thyroglobulin, PAX8 +) and typical thyroid carcinoma markers (CK19, HBME1, galectin-3) in most cases, and frequent CD56 loss. Molecular analysis of eight successful sequencing tumors revealed NRAS Q61 or HRAS Q61 mutations in three cases and a rare BRAF exon 11 (p.G469A) mutation in one PTC case. Novel EIF1AX/PTEN/KMT2C/BRCA1 alterations were identified in four cases. No TERT promoter mutations or RET/PTC fusions were detected. Tumors were assigned into RAS-like (5/8) and BRAF-like category (2/8) per WHO 2022 criteria; the remaining one tumor had no specifical mutations or related profiles. Clinically, all patients remain disease-free after surgery (follow-up 4-120months). In conclusions, MSO shares histomolecular overlap with primary thyroid carcinoma, validating WHO 2022 thyroid tumor classification for risk stratification in struma ovarii. Conservative surgical management achieves excellent outcomes in low-grade cases.

BackgroundCD44v6 is a membranous antigen upregulated in solid tumors and a promising molecular radiotherapy target, especially in anaplastic thyroid carcinoma (ATC). A Phase 1 trial recently launched to evaluate the lutetium-labeled anti-CD44v6 antibody [1⁷⁷Lu]Lu-DOTA-AKIR001 in CD44v6-positive solid tumors. Given limited data in non-ATC, we assessed CD44v6 immunoreactivity in tumors that may progress to a radioiodine-refractory state.Materials and MethodsAn exploratory cohort of 33 tumors (30 papillary thyroid carcinomas [PTCs], 3 poorly differentiated thyroid carcinomas [PDTCs]) was screened using the VFF-7 antibody, supported by detailed iodine concentration, genetic, and RNA sequencing data. A validation cohort of 40 oncocytic thyroid carcinomas (OTCs), 28 additional PDTCs, and one differentiated high-grade thyroid carcinoma was also screened using two antibody clones, VFF-7 and VFF-18.ResultsIn the exploratory cohort, 10 of 33 tumors (30%) showed focal or diffuse CD44v6 expression, while the rest were negative. Among OTCs in the validation cohort, 15 of 40 (38%) were partially or diffusely positive, and in PDTCs, 14 of 28 (50%) showed focal or diffuse staining. The VFF-7 and VFF-18 clones produced similar patterns.ConclusionsSubstantial subsets of non-ATCs express CD44v6, indicating that some patients may be candidates for [1⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy, particularly when conventional treatments are exhausted.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13044-025-00266-3.

Nodal Metastases in Oncocytic Carcinoma of the Thyroid Are Associated With Decreased Survival.

Thyroid tumours occur in patients with Birt-Hogg-Dubé syndrome (BHD), a condition caused by germline alterations in the FLCN gene that confers an increased cancer risk. Somatic FLCN mutations may also contribute to tumorigenesis. In this study, we present the first description of the cytopathology of two thyroid tumours evaluated by fine-needle aspiration (FNA) and harbouring pathogenic FLCN mutations. We encountered two patients with oncocytic thyroid tumours in which comprehensive next-generation sequencing (NGS) identified pathogenic FLCN mutations. We present the FNA cytologic findings and corresponding histopathology, and discuss the diagnostic challenges posed by the FNAs, one of which was initially confounded by negative preoperative molecular testing. Both patients were middle-aged females. Patient 1 had an incidental thyroid nodule and a history of BHD. FNA of a TI-RADS 5 mass was diagnosed as suspicious for papillary thyroid carcinoma (PTC), Bethesda V, leading to total thyroidectomy. Patient 2 presented with a palpable nodule. Compressive symptoms prompted lobectomy, revealing an angioinvasive oncocytic carcinoma. Subsequent FNA findings of a metastasis cytologically resembled oncocytic PTC; however, it was correctly diagnosed as oncocytic carcinoma after correlation with prior histologic findings. Expanded NGS testing facilitated the final diagnosis of FLCN-mutated oncocytic adenoma in Patient 1 and high-grade differentiated oncocytic carcinoma in Patient 2. Thyroid tumours harbouring FLCN mutations with oncocytic features may mimic PTC cytologically. Although rare, correct diagnosis of these tumours is essential to ensure appropriate treatment. For early detection, patients with BHD may benefit from thyroid ultrasound surveillance.

The incidence of follicular thyroid carcinoma (FTC) and oncocytic carcinoma of the thyroid has seldom been studied. However, thyroid cancer incidence has experienced significant increases globally over recent decades. This study aims to investigate the incidence of FTC and oncocytic carcinoma of the thyroid in Australia with particular attention to the impact of changes in the World Health Organization (WHO) endocrine tumour classification. Using incidence data from the Australian Institute of Health and Welfare cancer registry (spanning 1982-2019), this descriptive epidemiological study employed joinpoint regression analysis to assess temporal trends in FTC and oncocytic carcinoma of the thyroid. Results were then compared with WHO endocrine tumour classification changes over the same period to identify potential impact(s). FTC and oncocytic carcinoma of the thyroid accounted for 9.4 and 3.2% respectively, of all thyroid carcinomas. Oncocytic carcinoma of the thyroid incidence steadily increased across the study period. Subtype analysis of FTC showed the incidence of widely invasive FTC initially increased significantly before declining and was found to affect older adults primarily. On the other hand, minimally invasive FTC incidence rose sharply for both sexes. Encapsulated angioinvasive FTC, a recently classified subtype, was found predominantly in younger age groups, particularly the 30-34 age bracket. Changes in the incidence of FTC and oncocytic thyroid carcinoma are noted to be influenced by classification updates. To conclude, there is a steady rise in Australian FTC and oncocytic carcinoma of the thyroid incidence, influenced to some degree by WHO classification changes.

PurposeOncocytic carcinoma (OCA) has been reclassified from follicular thyroid carcinoma due to its unique features. Its rarity has resulted in limited studies on differentiating OCA from oncocytic adenoma (OA). This study aimed to compare the clinicopathologic and preoperative features of OCA and OA and evaluate the effectiveness of ultrasonography and cytology.MethodsWe conducted a retrospective study involving 83 patients (23 with OCA and 60 with OA) who underwent thyroid surgery between 2011 and 2024. We reviewed clinical, ultrasonographic, cytologic, and histopathologic data to assess diagnostic performance.ResultsOCA cases had larger tumors than OA in both sonographic (4.2 ± 1.7 cm vs. 2.7 ± 1.4 cm, P < 0.001) and pathologic measurements (3.8 ± 1.7 cm vs. 2.3 ± 1.4 cm, P < 0.001). K-TIRADS (the Korean Thyroid Imaging Reporting and Data System) did not effectively distinguish OCA from OA; however, ACR TI-RADS (the American College of Radiology Thyroid Imaging Reporting and Data System) categorized more OCA cases into higher-risk groups (17.4% vs. 1.7%, P = 0.016). Trabecular formation and intranodular vascularity were more frequent in OCA (17.4% vs. 1.7%, P = 0.019; 65.2% vs. 33.3%, P = 0.049). Cytologically, 87% of OCAs were classified as follicular neoplasms compared to 20% of OAs.ConclusionPredicting malignancy in oncocytic neoplasms is challenging. Larger tumor size, higher ACR TI-RADS scores, and trabecular formation are potential indicators for OCA. Cytologic subcategorization within Bethesda IV suggests follicular neoplasms carry a higher malignancy risk than oncocytic neoplasms. Multicenter studies are needed to validate these findings.

ABSTRACTObjectivesOncocytic thyroid carcinoma (OTC) is recognized as a distinct entity of follicular thyroid carcinoma (FTC), and its prognosis has traditionally been considered poor. However, the available data on this topic remain limited and highly heterogeneous. The objective of this study was to investigate the clinicopathological features and prognosis of patients with OTC and compare them with those of patients with FTC.MethodsA retrospective comparative study of all patients who underwent total thyroidectomy for OTC or FTC in a high‐volume endocrine surgery center between January 2005 and December 2021. Demographic and clinicopathological characteristics, complications, and recurrence rates were compared using univariate and multivariate regression analyses.ResultsIn total, 347 patients, 72% female, median age 48 years (35–61 years) were enrolled, including 123 with OTC and 224 with FTC. Patients were significantly older in the OTC group than in the FTC group (54.7 vs. 44.5 years, respectively, p = 0.001). With respect to other demographic, clinical, and pathological characteristics, no statistically significant differences were observed between the two groups. The median follow‐up duration was 5.6 years (3.2–10.5 years). Eighteen patients (5.2%) experienced recurrence, including 7 (5.7%) in the OTC group and 11 (4.9%) in the FTC group. No difference in recurrence‐free survival was observed between the OTC and FTC groups (p = 0.47). In multivariate analysis, histological type was not associated with the risk of recurrence.ConclusionPatients withOTC have the same recurrence rate as do patients with FTC . It does not appear justified to propose a different therapeutic management for this histological type, and a stepdown management could be proposed.

Oncocytic carcinomas of the salivary glands represent a rare and diverse group of malignancies characterised by granular eosinophilic cytoplasm due to abundant mitochondria. This review provides a comprehensive overview of oncocytic salivary gland carcinomas, categorised by their morphological patterns: monophasic, biphasic, and complex. Monophasic entities include oncocytic intraductal carcinoma (OIDC), oncocytic salivary duct carcinoma (OSDC), acinic cell carcinoma (ACC), and secretory carcinoma (SC). These tumours vary significantly in histological architecture, immunohistochemical profiles, and genetic alterations, ranging from TRIM33::RET fusions and BRAF V600E mutations in OIDC to NR4A3 rearrangements in ACC and ETV6::NTRK3 fusions in SC. Biphasic tumours, such as oncocytic epithelial-myoepithelial carcinoma (OEMC) and oncocytic adenocarcinoma not otherwise specified (OANOS), further complicate diagnosis due to dual cellular composition and overlapping features with other neoplasms. Complex-pattern tumours, particularly oncocytic mucoepidermoid carcinoma (OMEC), highlight diagnostic challenges and underscore the need for advanced molecular diagnostics. This article emphasises the critical role of integrated histopathological examination, immunohistochemical staining, and molecular profiling in the accurate classification of these neoplasms. Despite diagnostic advancements, some entities, like OANOS, remain provisional, pending widespread access to transcriptomic tools. Recognising the molecular heterogeneity and clinicopathologic nuances of oncocytic carcinomas is essential for improving diagnostic precision, prognostication, and guiding targeted therapy.