Dipti P. Sajed

Purpose: Salivary duct carcinoma (SDC) is the most common malignancy to arise in a pleomorphic adenoma (PA). Intracapsular or non-invasive carcinoma ex PA (CXPA) is defined by the presence of malignant-appearing tumor cells within the PA that do not violate the tumor border. Knowledge regarding the possible morphologic spectrum and prognosis of intratumoral CXPA is scarce. This study aims to evaluate the morphologic, immunohistochemical, and clinical features of PAs with apocrine / salivary-duct-like intratumoral atypia. Methods: Surgical pathology databases were queried for in situ or intracapsular/intratumoral SDC ex PAs and PAs with atypical epithelial cells (AEC). Exclusion criteria included recurrent lesions, invasion, positive margins, atypia only in myoepithelial cells, or other morphologic variants. Chromogenic multiplex (androgen receptor (AR) and HER2) and monoplex (p40) assays were performed on all available cases, as well as on a control group of non-atypical benign PAs and overtly invasive SDCs. Clinical outcomes were recorded. Results: 96 cases were identified: 23 AEC, 6 apocrine metaplasia, 41 benign PA, 8 SDC ex PA. All AEC, apocrine metaplasia, and benign cases were treated with surgery alone, with 3 AEC cases also receiving a neck dissection. No case recurred. Five of 8 SDC ex PA recurred; 3 died of disease. AR and HER2 were respectively expressed in 96% and 22–48% of AEC; 83% and 0% of apocrine metaplasia; 51% and 0% of benign PA; and 86–100% and 38–57% of SDC ex PA. Patients had increasing average age from benign (~ 50 years) to atypical/in situ (60 years) to invasive carcinoma (~ 70 years). Conclusion: The presence of epithelial atypia within a PA (ranging from isolated AR expression to apocrine metaplasia to overtly dysplastic/malignant epithelial cells) does not portend recurrence or metastasis if the atypia is confined within the borders of the adenoma and negative margins are achieved. Therefore, use of the term “in situ/intracapsular/intratumoral salivary duct carcinoma ex pleomorphic adenoma” is discouraged in light of good prognosis and potential for overtreatment by clinical teams. Nomenclature such as pleomorphic adenoma with epithelial “atypia” or “dysplasia” is recommended, followed by a comment regarding the morphologic features and likely indolent behavior.

Purpose Mesenchymal neoplasms composed of vascular, smooth muscle, and adipocytic components are uncommon in the nasal cavity. While angioleiomyoma (AL) is a smooth muscle tumor in the Head & Neck WHO classification, it is considered of pericytic origin in the Skin as well as Soft Tissue and Bone classifications. For nasal AL with an adipocytic component, the terms AL with adipocytic differentiation and angiomyolipoma (AML) have been applied, among others. AML is a type of perivascular epithelioid cell tumor (PEComa), most often arising in the kidney, sometimes associated with the tuberous sclerosis complex (TSC). It is uncertain whether nasal cavity AML and AL are best considered hamartomas or neoplasms, as their genetics are largely unexplored. Methods We performed a multi-institutional retrospective study of nasal cavity mesenchymal lesions. Patient demographics, clinical histories, and histologic and immunohistochemical findings were collected. DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissue and analyzed by SNP-based chromosomal microarray, targeted RNA fusion sequencing, and whole-exome sequencing. Results Fifteen lesions (3–42 mm) were identified, predominantly in male (87%) patients with a median age of 60. Patients typically presented with obstructive symptoms, and none had a history of TSC. One AL was a recurrence from six years prior; 11 cases showed no recurrence (median 4.7 years, range: 0.88–12.4). Morphologically, 11 AML contained 30–80% smooth muscle, 10–25% vasculature, and 2–60% adipose tissue, while four AL contained 70–80% smooth muscle and 20–30% vasculature. Other histologic observations included ulceration, thrombosis, inflammation, myxoid change, senescent nuclei, and extramedullary hematopoiesis; no well-developed epithelioid cell morphology was identified. Immunohistochemically, all cases were positive for smooth muscle markers (actin, desmin, and/or caldesmon) and negative for melanocytic markers. Molecular analysis revealed loss of 3p and 11q in a single AML. No other known pathogenic copy number or molecular alterations were seen, including in TSC1/2, TFE3, or NOTCH2. Conclusion Nasal cavity AML lacks morphologic, immunophenotypic, and genetic features of PEComa family AML. The significant histologic overlap between nasal AML and AL without distinguishing molecular features in either entity suggests “sinonasal angioleiomyoma with adipocytic differentiation” may be the most appropriate terminology for hybrid vascular and smooth muscle lesions containing adipocytic components.

Salivary gland classification has benefitted immensely from the growing field of molecular diagnostics. Microsecretory adenocarcinoma, a novel salivary gland malignancy recently included in the fifth edition of the World Health Organization Classifications of Head and Neck Tumours, is one such example. This novel entity was discovered among the umbrella category of adenocarcinoma, not otherwise specified, using a combination of careful histologic analysis and advanced molecular techniques. Its strikingly characteristic histologic features including subtle infiltration, flattened tubules, and abundant blue secretions highlight the necessity of meticulous morphologic observation, even in the age of increased molecular testing. It harbors a recurrent novel MEF2C::SS18 gene fusion, which is amenable to fluorescence in situ hybridization analysis. It presents predominantly in the oral cavity with a propensity for the palate and the majority are thus far low grade, clinically indolent tumors. The recent discovery of a cutaneous corollary to this tumor suggests that the spectrum of its presentation has not entirely been delineated. In the context of expanding molecular testing, pathologists are tasked to sift through constantly evolving molecular data to incorporate diagnostically relevant tests into their practice. In salivary gland pathology, the example of microsecretory adenocarcinoma demonstrates that primary histologic assessment, with sensible use of immunohistochemistry, can lead to accurate diagnosis. Molecular testing is beneficial in cases with significant diagnostic challenges.