Correlation between basal cell adenoma and basal cell adenocarcinoma of the salivary gland: a histomorphological and molecular review of 129 cases

Abstract

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are salivary gland tumors with biphasic differentiation, composed of luminal ductal cells and abluminal basal cells with a high nuclear-to-cytoplasmic ratio. While BCA is a relatively common benign tumor, BCAC is a rare malignancy, and its genetic context and relationship with BCA remain unclear. We investigated 93 BCA and 36 BCAC cases to further characterize these two tumor entities from histological and molecular perspectives. BCA/BCAC proliferated in a mixture of tubular, trabecular, solid, cribriform, and membranous patterns. A jigsaw puzzle pattern, peripheral palisading, S100-positive stroma, cystic change, and sclerosis were observed in approximately 50% of the cases. BCAC demonstrated the following malignant features: infiltration to surrounding tissue, tumor necrosis, and increased mitotic activity (81%, 22%, and 22%, respectively). The nuclear expression of β-catenin was frequently observed in both BCA and BCAC (89% and 60%), and CTNNB1 hotspot mutations were detected in 46% and 48% of BCA and BCAC cases, respectively. Tubular patterns of growth, jigsaw puzzle patterns, peripheral palisading, S100-positive stroma, and cystic changes were more common in β-catenin-positive BCA/BCAC than in β-catenin-negative BCA/BCAC. Among the β-catenin-negative BCA/BCAC cases, one case each harbored PLAG1 and MYB rearrangements. We concluded that β-catenin-positive BCA and BCAC share common histologic and molecular features, and BCAC is considered a malignant counterpart of BCA. β-Catenin-negative BCA/BCAC might include morphological mimickers, which can be genetically classified into other tumor types, including pleomorphic adenoma and adenoid cystic carcinoma.

Keywords: CTNNB1; Basal cell adenocarcinoma; Basal cell adenoma; Salivary gland tumor; β-catenin.

Fig. 1

Growth patterns and histologic features of basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC). The basaloid neoplastic cells of BCA/BCAC proliferate with a combination of several growth patterns (a: tubular pattern, b: trabecular pattern, c: solid pattern, d: cribriform pattern, and e: membranous pattern). In membranous patterns, the tumor cell nests are surrounded by dense hyaline material. (f) Nuclear palisading is observed at the periphery of the tumor cell nests. Tumor cell nests are separated by a narrow stromal component exhibiting a characteristic jigsaw puzzle pattern. Cystic changes (g) and sclerosis (h) are common features of BCA/BCAC. Myxoid stroma (i), squamous differentiation (j), and adjacent intercalated duct hyperplasia (IDH) (k, l) are the less frequently observed histological features. (k) Low-power view of the BCA (lower portion) and the adjacent IDH (upper portion). (l) High-power view of the IDH. IDH consists of small ducts with a minimal intervening stroma

Fig. 1

Growth patterns and histologic features of basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC). The basaloid neoplastic cells of BCA/BCAC proliferate with a combination of several growth patterns (a: tubular pattern, b: trabecular pattern, c: solid pattern, d: cribriform pattern, and e: membranous pattern). In membranous patterns, the tumor cell nests are surrounded by dense hyaline material. (f) Nuclear palisading is observed at the periphery of the tumor cell nests. Tumor cell nests are separated by a narrow stromal component exhibiting a characteristic jigsaw puzzle pattern. Cystic changes (g) and sclerosis (h) are common features of BCA/BCAC. Myxoid stroma (i), squamous differentiation (j), and adjacent intercalated duct hyperplasia (IDH) (k, l) are the less frequently observed histological features. (k) Low-power view of the BCA (lower portion) and the adjacent IDH (upper portion). (l) High-power view of the IDH. IDH consists of small ducts with a minimal intervening stroma

Fig. 2

Immunohistochemical and genetic findings of BCA/BCAC. (a) Luminal ductal cells are strongly positive for CK7 (left) whereas basal cells are positive for p63 (right). (b) S100-positive stromal cells are present. (c) The nuclear expression of β-catenin is restricted to a subset of basal cells, while luminal ductal cells are consistently negative for β-catenin. Additionally, some S100-positive spindle stromal cells are positive for β-catenin (inset). (d) Sanger sequencing of the CTNNB1 p.I35T variant

Fig. 3

Invasion, infiltration, nuclear atypia, and necrosis in BCA and BCAC. Capsular invasion (a) and pseudopodia (b) of BCA. These findings are not diagnostic features of a malignancy. c–f Malignant features of BCAC. c Infiltration of the surrounding tissue is the major diagnostic criterion for BCAC. This patient was positive for nuclear β-catenin. d Perineural invasion. This patient was positive for nuclear β-catenin and harbored the CTNNB1 p.I35T variant. e Vascular invasion. This patient was negative for nuclear β-catenin. f Necrosis. This patient was negative for nuclear β-catenin. g Severe nuclear atypia. This patient was positive for nuclear β-catenin and harbored the CTNNB1 p.I35T variant