Oncocytic Lesions of Salivary Glands: Morphological, Immunohistochemical, and Molecular Findings.

The fifth edition of the World Health Organization (WHO) classification introduces new diagnostic methods based on genetic alterations, providing insight into the molecular basis of lesions. As a result, the classification system has evolved, new entities have been introduced, and existing entities have been reclassified. Oncocytic lesions of salivary glands are a group of neoplastic conditions characterized by the presence of oncocytic cells. These lesions present a diagnostic challenge due to their overlapping histological features. Therefore, a comprehensive evaluation, including morphological, immunohistochemical, and molecular analysis, is crucial for accurate diagnosis and appropriate management. Accurate classification of salivary gland pathologies is essential for selecting the appropriate treatment methods and predicting outcomes. The introduction of new therapeutic approaches, such as targeted therapies for malignant salivary gland tumors, has improved patient outcomes. However, to effectively implement these therapies in clinical practice, a clear classification of lesions is necessary.

Cytopathology approach to rare salivary gland lesions with oncocytic features.

Salivary glands located in the head and neck area are known to have different lesions with prominent oncocytic features. Fine needle aspiration is usually the initial approach in the management of these lesions, whether they represent neoplastic or non-neoplastic processes. Owing to the limited material present upon cytopathologic examination, knowledge of variants and subtypes of various oncocytic lesions that can occur in this area is of major importance to provide the most accurate interpretation to the patients and clinicians. In this article, we selected rare lesions of the salivary glands that may exhibit oncocytic changes, and provided a brief discussion of each one of them, with emphasis on challenges in navigating the differential diagnosis that these cases may pose, from the cytopathology standpoint.

High-resolution genomic profiling of thyroid lesions uncovers preferential copy number gains affecting mitochondrial biogenesis loci in the oncocytic variants.

Oncocytic change is the result of aberrant mitochondrial hyperplasia, which may occur in both neoplastic and non-neoplastic cells and is not infrequent in the thyroid. Despite being a well-characterized histologic phenotype, the molecular causes underlying such a distinctive cellular change are poorly understood. To identify potential genetic causes for the oncocytic phenotype in thyroid, we analyzed copy number alterations in a set of oncocytic (n=21) and non-oncocytic (n=20) thyroid lesions by high-resolution microarray-based comparative genomic hybridization (aCGH). Each group comprised lesions of diverse histologic types, including hyperplastic nodules, adenomas and carcinomas. Unsupervised hierarchical clustering of categorical aCGH data resulted in two distinct branches, one of which was significantly enriched for samples with the oncocytic phenotype, regardless of histologic type. Analysis of aCGH events showed that the oncocytic group harbored a significantly higher number of genes involved in copy number gains, when compared to that of conventional thyroid lesions. Functional annotation demonstrated an enrichment for copy number gains that affect genes encoding activators of mitochondrial biogenesis in oncocytic cases but not in their non-oncocytic counterparts. Taken together, our data suggest that genomic alterations may represent additional/alternative mechanisms underlying the development of the oncocytic phenotype in the thyroid.

CBX7 Expression in Oncocytic Thyroid Neoplastic Lesions (Hürthle Cell Adenomas and Carcinomas).

BACKGROUND: Previous analysis of CBX7 expression in a large number of thyroid adenoma and carcinoma samples revealed a progressive reduction of CBX7 levels that was well related with the malignant grade of thyroid neoplasias. Hürthle cell tumors are unusual thyroid neoplasms characterized by the presence of particular cells called oncocytes. OBJECTIVES: In order to develop new tools for a more accurate diagnosis of Hürthle cell tumors of the thyroid, we evaluated CBX7 protein levels to verify the possible presence of an expression signature. METHODS: CBX7 expression was evaluated by immunohistochemistry in a panel of thyroid tissue sections including normal thyroids, goiters, follicular adenomas and oncocytic lesions. RESULTS: CBX7 expression was low or null in 68% of Hürthle adenomas, whereas it was comparable to normal thyroid tissue in Hürthle hyperplasias and follicular adenomas. CONCLUSIONS: Reduced expression of CBX7 suggests a more aggressive identity of Hürthle adenomas with respect to non-Hürthle ones.