Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment

Abstract

Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50 years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in well-known oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.

Keywords: androgen receptor; fine-needle aspiration; human epidermal growth factor receptor 2; salivary duct carcinoma; salivary gland tumor; targeted therapy.

FIGURE 1.

Contrast-enhanced computed tomography images of salivary duct carcinoma (SDC) in (A) the parotid gland and (B) the submandibular gland. SDCs (arrowheads) exhibit a heterogeneously enhanced mass with an ill-defined border. Occasional calcification and necrosis are noted.

FIGURE 2.

Histology and immunohistochemistry of salivary duct carcinoma (SDC). (A) Low-power view of an SDC tumor shows tumor cell proliferation with comedo-type central necrosis resembling breast ductal carcinoma. (B) Tumor cells of SDC have large nuclei with conspicuous nucleoli and abundant eosinophilic cytoplasm. (C) Sarcomatoid SDC. Abrupt transition from conventional SDC (left portion) to fascicular proliferation of highly atypical spindle cells is observed. (D) SDC ex pleomorphic adenoma. Ducts composed of atypical SDC cells (left portion) abut myxochondroid stroma of preexisting pleomorphic adenoma (right portion). (E) Invasive morphology of the tumor front. Many tumor buds (nests comprising <4 cells, indicated with arrows) and poorly differentiated clusters (nests comprising >5 cells, indicated with arrowheads) are observed. (F) Diffuse and strong immunohistochemical staining for androgen receptor (left panel) and human epidermal growth factor receptor 2 (right panel).

FIGURE 3.

Fine needle aspiration of salivary duct carcinoma (SDC). (A) A low-power view shows 3-dimensional pseudopapillary clusters of tumor cells. (B) Tightly cohesive cluster with nuclear crowding. Tumor cells show nuclear pleomorphism suggestive of high-grade malignant tumor. (C) Loose cell clusters are observed in a necrotic background. Tumor cells have large pleomorphic nuclei with coarse chromatin and conspicuous nucleoli and abundant eosinophilic cytoplasm. (D) Isolated tumor cells in the aspirates have round to oval nuclei and abundant cytoplasm. Markedly enlarged nucleus, mutinucleation, and cannibalism are noted. (E) Aspirate from a sarcomatoid SDC tumor shows isolated atypical spindle cells on a hemorrhagic background. (F) Immunohistochemical staining of a formalin-fixed cell block specimen. Tumor cells express androgen receptor (left panel) and human epidermal growth factor receptor 2 (right panel).