Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands

Abstract

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.

Keywords: Classification; Gene fusion; Neoplasm; Salivary gland; WHO; World Health Organization.

Fig. 1

Sclerosing polycystic adenoma (SPA). SPA is well circumscribed and encapsulated tumor composed of proliferations of ducts and acini within fibrotic stroma sometimes intermixed with foci of mature adipose tissue (Fig. 1A). The halmark of SPA is a presence acinic cells with abundant large eosinophilic cytoplasmic granules (Fig. 1B). Ductal structures are surrounded by periductal concentric layers of stromal hyalinization (Fig. 1C). SPA frequently harbors intraductal epithelial proliferations with variable degree of atypia. Low-grade atypia is composed of intercalated duct-like epithelium positive for SOX10 (Fig. 1D, E) and high-grade atypia with atypical nuclear features and complex growth pattern of micropapillary structures with luminal apocrine epithelium positive for AR (Fig. 1F, G). Invasive carcinoma arising in SPA is presented in Fig. 1H–J. Well circumscribed predominantly polycystic SPA divided from parotid gland by fibrous pseudocapsule is seen in the left upper part of the picture (Fig. 1H) while Figs. 1I andJ show invasive salivary duct carcinoma and apocrine intraductal carcinoma, respectively

Fig. 2

Keratocystoma. Keratocystoma is composed of multicystic spaces (Fig. 2A), lined by stratified squamous epithelium, containing keratotic lamellae (Fig. 2B). Squamous epithelium shows a parakeratotic or orthokeratotic surface, usually without a granular cell layer (Fig. 2C). (courtesy of Dr. Toshitaka Nagao)

Fig. 3

Intercalated duct adenoma (IDA) (Fig. 3A, B) and striated duct adenoma (SDA) (Fig. 3C, D). IDA is composed of bilayered ducts with a cytological appearance and immunoprofile of normal intercalated ducts (Fig. 3A). High power image shows spindle shaped abluminal myoepithelial cell layer (Fig. 3B). SDA is composed of ducts lined by a monolayer of cells resembling normal striated ducts (Fig. 3C) and do not contain myoepithelial or basal cells. Only occasional abluminal cells are decorated by smooth muscle actin (Fig. 3D)

Fig. 4

Microsecretory adenocarcinoma (MSA). MSA is small tubules and microcysts lined by flat intercalated duct-like cells, and containing abundant basophilic luminal secretions (Fig. 4A, B). Tumor cells show diffuse positivity for p63 (Fig. 4C), S100 protein (Fig. 4D) and SOX10 (Fig. 4E). Next generation sequencing of MSA shows a recurrent MEF2C::SS18 gene fusion (Fig. 4F). (courtesy of Dr. Justin Bishop)

Fig. 5

Sclerosing microcystic adenocarcinoma (SMA). SMAs consist of small infiltrative cords and nests embedded in thick fibrous or desmoplastic stroma (Fig. 5A). Perineural invasion is common (Fig. 5B). (courtesy of Dr. Abbas Agaimy)

Fig. 6

Intraductal carcinoma (IC). IC typically shows an intercalated duct phenotype demonstrating SOX10 positivity of luminal cells (Fig. 6A, B), while a subset of IC shows apocrine morphology supported by androgen receptor positivity (Fig. 6C, D)

Fig. 7

Polymorphous adenocarcinoma, cribriform subtype (CASG). CASG is characterized by a multinodular growth pattern separated by fibrous septa, with predominant glomeruloid, cribriform and microcystic architecture (Fig. 7A, B). Optically clear nuclei with resemblance to “Orphan Annie Eyes” and papillary structures (Fig. 7C) are typically observed but in contrasat to papillary thyroid cancer, the tumor cells are S100 protein positive (Fig. 7D)