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Head and Neck Pathology Mar 2022The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several...
The salivary gland section in the 5th edition of the World Health Organization Classification of Head and Neck Tumours features a description and inclusion of several new entities, including sclerosing polycystic adenoma, keratocystoma, intercalated duct adenoma, and striated duct adenoma among the benign neoplasms; and microsecretory adenocarcinoma and sclerosing microcystic adenocarcinoma as the new malignant entities. The new entry also includes mucinous adenocarcinoma subdivided into papillary, colloid, signet ring, and mixed subtypes with recurrent AKT1 E17K mutations across patterns suggesting that mucin-producing salivary adenocarcinomas represent a histologically diverse single entity that may be related to salivary intraductal papillary mucinous neoplasm (IPMN). Importantly, the number of entities in the salivary chapter has been reduced by omitting tumors or lesions if they do not occur exclusively or predominantly in salivary glands, including hemangioma, lipoma, nodular fasciitis and hematolymphoid tumors. They are now discussed in detail elsewhere in the book. Cribriform adenocarcinoma of salivary gland origin (CASG) now represents a distinctive subtype of polymorphous adenocarcinoma (PAC). PAC is defined as a clinically, histologically and molecularly heterogeneous disease group. Whether CASG is a different diagnostic category or a variant of PAC is still controversial. Poorly differentiated carcinomas and oncocytic carcinomas are discussed in the category "Salivary carcinoma not otherwise specified (NOS) and emerging entities". New defining genomic alterations have been characterized in many salivary gland tumors. In particular, they include gene fusions, which have shown to be tightly tumor-type specific, and thus valuable for use in diagnostically challenging cases. The recurrent molecular alterations were included in the definition of mucoepidermoid carcinoma, adenoid cystic carcinoma, secretory carcinoma, polymorphous adenocarcinoma, hyalinizing clear cell carcinoma, mucinous adenocarcinoma, and microsecretory adenocarcinoma.
Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adenoma; Biomarkers, Tumor; Humans; Salivary Gland Neoplasms; Salivary Glands; World Health Organization
PubMed: 35312980
DOI: 10.1007/s12105-022-01420-1 -
Surgical Pathology Clinics Mar 2021Myoepithelial carcinoma (MECA) may overlap histologically with other salivary gland neoplasms, especially pleomorphic adenoma. MECA is characterized by cellular, uniform... (Review)
Review
Myoepithelial carcinoma (MECA) may overlap histologically with other salivary gland neoplasms, especially pleomorphic adenoma. MECA is characterized by cellular, uniform growth of myoepithelial cells and multinodular expansile invasive pattern with zonal cellular distribution. It may arise de novo or in association with pleomorphic adenoma (myoepithelial carcinoma ex pleomorphic adenoma). By immunohistochemistry, MECA is positive for cytokeratins and at least one of the myoepithelial markers, including S100. PLAG1 fusion is the most common genetic alteration. Carcinoma ex pleomorphic adenoma and necrosis correlate with worse clinical outcome in MECA, and necrosis can be used to stratify MECA as high grade.
Topics: Adenoma, Pleomorphic; Diagnosis, Differential; Epithelial Cells; Humans; Immunohistochemistry; Myoepithelioma; Necrosis; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Prognosis; Salivary Gland Neoplasms
PubMed: 33526224
DOI: 10.1016/j.path.2020.09.008 -
Neoplasia (New York, N.Y.) May 2021Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been...
Diagnosis of salivary gland neoplasms is often challenging due to their high morphological diversity and overlaps. Several recurrent molecular alterations have been described recently, which can serve as powerful diagnostic tools and potential therapeutic targets (e.g. NTRK or RET fusions). However, current sequential molecular testing can be expensive and time consuming. In order to facilitate the diagnosis of salivary gland neoplasms, we designed an all-in-one RNA-based next generation sequencing panel suitable for the detection of mutations, fusions and gene expression levels (including NR4A3) of 27 genes involved in salivary gland neoplasms. Here we present the validation of the "SalvGlandDx" panel on FFPE histological specimen including fine needle aspiration (FNA) cell block material, against the standard methods currently used at our institution. In a second part we describe selected unique cases in which the SalvGlandDx panel allowed proper diagnosis and new insights into special molecular characteristics of selected salivary gland tumors. We characterize a unique salivary gland adenocarcinoma harboring a ZCCHC7-NTRK2 fusion, a highly uncommon spindle cell and pseudoangiomatoid adenoid-cystic carcinoma with MYBL1-NFIB fusion, and a purely oncocytic mucoepidermoid carcinoma, whereas diagnosis could be made by detection of a CRTC3-MAML2 rearrangement on the cell block specimen of the FNA. Further, a rare case of a SS18-ZBTB7A rearranged low-grade adenocarcinoma previously described as potential spectrum of microsecretory adenocarcinoma, is reported. In addition, features of six cases within the spectrum of polymorphous adenocarcinoma / cribriform adenocarcinoma of salivary gland including PRKD1 p.E710D mutations and novel fusions involving PRKAR2A-PRKD1, SNX9-PRKD1 and ATL2-PRKD3, are described.
Topics: Biomarkers, Tumor; Biopsy; Cell Line, Tumor; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Mutation; Neoplasm Grading; Neoplasm Staging; Oncogene Proteins, Fusion; Salivary Gland Neoplasms
PubMed: 33878706
DOI: 10.1016/j.neo.2021.03.008 -
Archives of Pathology & Laboratory... Dec 2023Salivary gland neoplasms are rare lesions in the head and neck (H&N) pathology realm. There are more than 20 malignant and 15 benign salivary gland neoplasms in the 5th... (Review)
Review
CONTEXT.—
Salivary gland neoplasms are rare lesions in the head and neck (H&N) pathology realm. There are more than 20 malignant and 15 benign salivary gland neoplasms in the 5th edition of the World Health Organization classification of H&N tumors. These neoplasms consist of heterogeneous groups of uncommon diseases that make diagnosis and treatment challenging for the clinical team. Using an algorithmic immunohistochemical approach-defined tumor origin and type has proven to be effective and advantageous. Immunohistochemistry may be used as sort of a "diagnostic looking glass," not as a positive or negative type tool, but as an indispensable complement to a hematoxylin-eosin morphologic pattern-based approach. Furthermore, the understanding of the novel discoveries of the salivary gland gene fusions and the molecular aspects of these tumors makes the process easier and improve the diagnosis as well as treatment aspects. This review reflects our experience with more recent diagnostic antibodies, which include MYB RNA, Pan-TRK, PLAG1, LEF1, and NR4A3. Each of these is linked with a specific type of neoplasm; for example, gene fusions involving the PLAG1 and HMGA2 oncogenes are specific for benign pleomorphic adenomas, and MYB is associated with adenoid cystic carcinoma.
OBJECTIVE.—
To review these more recent antibodies, which highly enhance salivary gland neoplasm diagnosis.
DATA SOURCES.—
The study sources involved literature PubMed searches, including multiple review articles, case reports, selected book chapters, and Geisinger Medical Center cases.
CONCLUSIONS.—
Salivary gland tumors are a rare, varied group of lesions in H&N pathology. We need to have continuous readings and revisions of the molecular consequences of these fusion oncoproteins and their subsequent targets, which will eventually lead to the identification of novel driver genes in salivary gland neoplasms.
Topics: Humans; Immunohistochemistry; Salivary Gland Neoplasms; Adenoma, Pleomorphic; Salivary Glands; Carcinoma, Adenoid Cystic; Transcription Factors; Biomarkers, Tumor
PubMed: 37074867
DOI: 10.5858/arpa.2022-0461-RA -
Modern Pathology : An Official Journal... Jan 2017This review concentrates on three salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma... (Review)
Review
This review concentrates on three salivary gland tumors that have been accepted in the recent literature as new neoplastic entities: mammary analog secretory carcinoma (MASC), sclerosing polycystic adenoma (SPA) and cribriform adenocarcinoma of tongue and other minor salivary glands (CAMSGs). MASC is a distinctive low-grade malignant salivary cancer that harbors a characteristic chromosomal translocation, t(12;15) (p13;q25) resulting in an ETV6-NTRK3 fusion. SPA is a rare lesion often mistaken histologically for low-grade salivary carcinoma. Previously thought to be a reactive fibroinflammatory process, but recent evidence of clonality, recurrences in up 30%, and dysplastic foci suggest it may be truly neoplastic. CAMSG is a distinct tumor entity that differs from polymorphous low-grade adenocarcinoma (PLGA) by location (ie, most often arising on the tongue), by prominent nuclear clearing, alterations of the PRKD gene family and clinical behavior with frequent metastases at the time of presentation of the primary tumor. Early metastatic disease seen in most cases of CAMSG associated with indolent behavior makes it a unique neoplasm among all low-grade salivary gland tumors. Salivary glands may give rise to a wide spectrum of different tumors. They are often diagnostically challenging as morphological features often overlap between different entities. Although conventional morphology in combination with immunohistochemical findings still provide the most important clues for diagnosis, recent advances in molecular pathology offer new diagnostic tools in investigating the differential diagnosis, as well as providing potentially valuable prognostic indicators. In the last two decades, several new salivary gland tumor entities have been described, namely MASC, SPA and CAMSGs.
Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Humans; Mammary Analogue Secretory Carcinoma; Oncogene Proteins, Fusion; Prognosis; Salivary Gland Neoplasms
PubMed: 28060365
DOI: 10.1038/modpathol.2016.167 -
International Journal of Molecular... Jun 2021Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma,... (Review)
Review
Salivary gland tumors are a rare tumor entity within malignant tumors of all tissues. The most common are malignant mucoepidermoid carcinoma, adenoid cystic carcinoma, and acinic cell carcinoma. Pleomorphic adenoma is the most recurrent form of benign salivary gland tumor. Due to their low incidence rates and complex histological patterns, they are difficult to diagnose accurately. Malignant tumors of the salivary glands are challenging in terms of differentiation because of their variability in histochemistry and translocations. Therefore, the primary goal of the study was to review the current literature to identify the recent developments in histochemical diagnostics and translocations for differentiating salivary gland tumors.
Topics: Biomarkers, Tumor; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Humans; Neoplasm Grading; Neoplasm Staging; Preoperative Care; Salivary Gland Neoplasms; Translocation, Genetic
PubMed: 34202474
DOI: 10.3390/ijms22136771 -
Archives of Pathology & Laboratory... Sep 2016Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement... (Review)
Review
Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.
Topics: Diagnosis, Differential; Humans; In Situ Hybridization, Fluorescence; Mammary Analogue Secretory Carcinoma; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Prognosis; Salivary Gland Neoplasms; Salivary Glands
PubMed: 27575269
DOI: 10.5858/arpa.2015-0075-RS -
Cancer May 2020Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment.
BACKGROUND
Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment.
METHODS
Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM.
RESULTS
Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003).
CONCLUSIONS
In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Incidence; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Risk Factors; Salivary Gland Neoplasms; Sex Characteristics; Survival Analysis; Young Adult
PubMed: 32097509
DOI: 10.1002/cncr.32792 -
International Journal of Molecular... Nov 2022Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality.... (Review)
Review
Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality. Nevertheless, some malignancies have a tendency of recurrence, with possible distant metastasis. Alternative treatment strategies, such as primary radiation or chemotherapeutics, often present low response rates. As a result, there is an unmet need for novel therapeutic approaches. Nowadays, target-based therapies (e.g., small inhibitors and immunotherapy) are used by the medical oncologist for possible treatment of advanced SGMs. Based on recent published trials, some novel treatments may provide additional disease control for some patients. However, sample sizes are small, the general findings are unsatisfactory, and a lot of uncertainties remain to be elucidated. Nevertheless, research shows that patients do not benefit from blind administration of systemic treatments and therefore a more personalized approach is highly needed. The aim of this review paper is to summarize the most recent advances in the biological understanding and molecular pathways of salivary gland cancers, the association of these pathways with the current treatments used and their implications for more personalized targeted-based therapies.
Topics: Humans; Salivary Gland Neoplasms; Head and Neck Neoplasms
PubMed: 36499216
DOI: 10.3390/ijms232314891 -
Cancer Cytopathology Apr 2022Fine-needle aspiration (FNA) is the preferred diagnostic test for salivary gland lesions. The purpose of the Milan System for Reporting Salivary Gland Cytopathology...
Utility of the Milan System for Reporting Salivary Gland Cytology, with focus on the incidence and histologic correlates of atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP): A 3-year institutional experience.
BACKGROUND
Fine-needle aspiration (FNA) is the preferred diagnostic test for salivary gland lesions. The purpose of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is to standardize salivary gland cytology reporting and guide treatment decisions. The objective of the current study was to evaluate the utility and performance of the MSRSGC, with a focus on the cytomorphology of lesions diagnosed as atypia of undetermined significance (AUS) and salivary gland neoplasm of uncertain malignant potential (SUMP).
METHODS
In total, 123 salivary gland FNAs were included in the study. FNA diagnoses for all cases were reviewed and recategorized, as applicable, according to the MSRSGC. Cytohistologic correlation was performed in 51 cases that had available surgical follow-up, and the risk of malignancy (ROM) was calculated.
RESULTS
Most FNA samples were from the parotid gland. The mean patient age was 61.4 years, and the male-to-female ratio was 1.3:1. The ROM was 0% (categories I and II; nondiagnostic and benign nonneoplastic, respectively), 50% (category III; AUS), 0% (category IVA; benign neoplasm), 40% (category IVB; SUMP), 100% (category V; suspicious for malignancy), and 100% (category VI; malignant). Sensitivity, specificity, positive predictive value, and negative predictive value were 100% each. In addition, the primary factors for an AUS diagnosis were identified as low cellularity and/or the presence of lymphocytes. The presence of oncocytes followed by cellular atypia in an otherwise classic pleomorphic adenoma were principal factors for a SUMP diagnosis.
CONCLUSIONS
The authors report an ROM comparable to that reported in the literature, with a sensitivity and specificity of 100%, supporting adaptation of the MSRSGC into the system for reporting salivary gland cytology. In addition, the findings emphasize the need to refine criteria for AUS and SUMP, thereby improving the predictive capability and subsequent management of salivary gland lesions.
Topics: Cytodiagnosis; Female; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Salivary Gland Neoplasms; Salivary Glands
PubMed: 34875145
DOI: 10.1002/cncy.22538