Historical Evolution of the Polymorphous Adenocarcinoma

Abstract

The 2017 World Health Organization Classification of Head and Neck Tumors introduced for the first time the diagnostic terminology "cribriform variant of polymorphous adenocarcinoma". This nomenclature attempts to reconciliate the ongoing taxonomical controversy related to cribriform adenocarcinoma of tongue. In order to better understand this classification conundrum, it is imperative for pathologist to comprehend the historical evolution of polymorphous adenocarcinoma formerly known as polymorphous "low grade" adenocarcinoma. This review highlights our understanding of these tumors since their origins.

Keywords: Cribriform adenocarcinoma of tongue; Cribriform variant of polymorphous adenocarcinoma; Minor salivary gland; PRDK1; PRDK2; PRKD3; Polymorphous adenocarcinoma; Polymorphous low grade adenocarcinoma.

Fig. 1

In summary, polymorphous adenocarcinoma (PA) was first described by two different groups in 1983 as terminal duct carcinoma and lobular carcinoma of minor salivary glands. Subsequently, it was renamed as polymorphous low-grade adenocarcinoma (PLGA) in 1984 and included as such in the 1991 WHO classification of salivary gland tumors as a distinct entity. In 1999, cribriform adenocarcinoma of the tongue (CAT) was proposed as different and distinct entity, based on its localization to the base of the tongue, morphologic features including glomeruloid/cribiform structures and nuclear features reminiscent of papillary thyroid carcinoma, and clinical behavior including the presence of synchronous lymph node metastasis. The 2005 WHO classification did not recognize CAT as a distinct tumor but as a possible variant of PLGA. Since them CAT has been reported at other anatomic sites. In 2014 rearrangements in PRKD 1–3 were reported in CAT and PRDK1 point mutations in PLGA. In the 2017 WHO classification, a terminology change was presented to include renaming PLGA as PA and owing to overlapping morphological and molecular features to subsume CAT within the classification of PA and referring to it as the cribriform variant of PA

Fig. 2

Polymorphous adenocarcinoma (PA) is classically characterized by an invasive unencapsulated neoplastic proliferation showing diverse morphological patterns (a, Hematoxylin & Eosin [H&E] stained slide at 2 × 10 magnification); single cell filing and perineural invasion with concentric whorling are commonly identified (c, H&E stained slide at 10 × 10 magnification); tumor cells are bland, small to medium in size and have oval nuclei with open chromatin and inconspicuous to small nucleoli (e, H&E stained slide at 60 × 10 magnification). Cribriform variant of PA is predominately characterized by a cellular proliferation divided by fibrous septa into tumor nodules (b, H&E stained slide at 2 × 10 magnification); some nodules are detached from the surrounding fibrous stroma imprinting a glomeruloid appearance (d, H&E stained slide at 10 × 10 magnification); tumor cells are bland with clear to light eosinophilic cytoplasm and overlapping nuclei showing optical clearing reminiscent nuclei features of papillary thyroid carcinoma (f, H&E stained slide at 60 × 10 magnification)