Don't SUMP it! Utility of PLAG1 immunocytochemistry in basaloid SUMP subcategory

Abstract

BackgroundBasaloid salivary gland neoplasm of uncertain malignant potential (B‐SUMP) is an indeterminate diagnostic subcategory, with pleomorphic adenoma (PA) representing the most common benign neoplasm. Pleomorphic adenoma gene 1 (PLAG1) staining is frequently seen in PAs and could aid in distinguishing them from other basaloid neoplasms. The authors evaluated the utility of PLAG1 immunocytochemistry (ICC) in differentiating PAs from other basaloid neoplasms in smears and liquid‐based cytology (LBC) specimens.MethodsIn total, 45 B‐SUMP cytology aspirates and corresponding surgical excision specimens were identified. PLAG1 immunostaining was performed in all aspirates and surgical excision specimens and was scored as positive (strong/diffuse), equivocal (focal/weak), or negative.ResultsPLAG1 ICC was performed directly on 38 smears and seven LBC specimens. PLAG1 was positive in 29 of 45 cases (64%), whereas six of 45 (13%) were equivocal, and 10 of 45 (22%) were negative. PLAG1‐positive aspirates included 26 (90%) PAs, two (7%) basal cell adenomas (BCAs), and one (3%) carcinoma ex‐PA. PLAG1‐equivocal aspirates included four (67%) PAs and two (33%) BCAs, whereas negative aspirates included five (50%) BCAs, four (40%) adenoid cystic carcinomas, and one (10%) metastatic adenosquamous carcinoma. The sensitivity, specificity, positive, and negative predictive values were 87%, 86%, 93%, and 75%, respectively. Diagnostic accuracy was 87%.ConclusionsPLAG1 ICC is useful when positive (strong/diffuse) and can be reliably performed on smears and LBC specimens. PLAG1 was positive in most PAs and in a small subset of BCAs. Therefore, in the absence of atypical cytologic features, PLAG1‐positive tumors could be diagnosed as benign, with a note favoring PA versus BCA. In contrast, PLAG1‐negative/equivocal tumors should remain in the B‐SUMP category.

Molecular analysis using SalvGlandDx improves risk of malignancy estimation and diagnosis of salivary gland cytopathology: An exploratory multicenter study

“…Interestingly, the Although nonspecific for PA, the PLAG1-positive cases were most frequently found in benign PA, and moreover in BCA. 14 These data further corroborate our findings that, in the absence of atypical features, PLAG1 rearrangements are most frequently found in the spectrum of cellular PA. Nevertheless, PLAG1 rearrangements can also be detected in myoepithelioma and myoepithelial carcinoma (de novo or ex PA); thus, detection must always be correlated with morphology (monophasic vs. multiphasic neoplasia).…”

Is molecular testing of salivary gland FNA specimens ready for prime time?

“…However, the case demonstrated cytologic atypia, and was therefore morphologically classified as Milan V. Although nonspecific for PA, the PLAG1-positive cases were most frequently found in PA. These data further corroborate the findings from Sanchez-Avila et al 9 that, in the absence of atypical features, PLAG1 rearrangements are most frequently found in the spectrum of cellular PA. This suggests that finding PLAG1 in a basaloid SUMP (by IHC and/or NGS) may allow for a reclassification into Milan IVA category.…”

“…Accordingly, there are several ancillary diagnostic tools at our disposal including IHC, fluorescent in situ hybridization (FISH), and more recently next-generation sequencing (NGS) technologies, which can all be successfully applied to FNA specimens, provided there is adequate material to do so. 1,[6][7][8][9][10] The most common ancillary studies performed on salivary gland FNA include IHC, histochemistry, and FISH, and cell blocks prepared from aspirated salivary gland lesions is the preferred and most convenient material. [6][7][8][9][10] In contrast, NGS is only rarely used by cytopathologists for salivary glands aspirates.…”

“…1,[6][7][8][9][10] The most common ancillary studies performed on salivary gland FNA include IHC, histochemistry, and FISH, and cell blocks prepared from aspirated salivary gland lesions is the preferred and most convenient material. [6][7][8][9][10] In contrast, NGS is only rarely used by cytopathologists for salivary glands aspirates. 6,8,[11][12][13][14] Moreover, the choice of the ancillary technique test depends largely on the institution's budget, available platforms, and expertise of trained staffs.…”

“…6 Furthermore, there are now several commercially available IHC markers, including PLAG-1, MYB, pan-TRK, and NR4A3, that can serve as surrogates for underlying molecular alterations, contributing to the accurate diagnosis and representing a convenient and inexpensive alternative to NGS. 1,[6][7][8][9][10] Over the last few years, some institutions have developed their own comprehensive customizable NGS with broad panels specifically designed to cover most gene alterations, including mutations, fusions ,and RNA gene expression alterations in salivary gland tumors. 3,12,14 Among them, the SalvGlandDx panel is an all-in-one RNA-based NGS panel for the detection of mutations, fusions and gene expression levels of 27 genes involved in salivary gland tumors.…”