Section 4 -

Basaloid Tumors (Dr. Faquin) William C. Faquin, M.D., Ph.D. Celeste N. Powers, M.D., Ph.D.

Clinical History: A 45 year-old man with a 6 month history of a 3.7 cm mildly painful, enlarging left parotid gland mass. An MRI showed a nodular, slightly irregular lesion with variable signal intensity located in the superficial parotid gland just lateral to the facial nerve. An FNAB was performed. Cytologic Findings: The smears were moderately cellular and showed cohesive clusters of small uniform basaloid cells with hyperchromatic, cytologically bland oval nuclei with indistinct nucleoli, scant cytoplasm, and small amounts of dense homogeneous metachromatic hyaline matrix material between cells. A second population of larger cells with bland pale oval to elongate nuclei and a moderate amount of delicate cytoplasm was also present. The population of small basaloid cells tended to be present around the periphery of cell clusters. Mitotic activity and necrosis were not identified, and at most slight nuclear atypia in the form of mild nuclear pleomorphism was seen. The background contained blood, some bland naked nuclei, and occasional scattered single cells. Based upon these findings, a cytologic diagnosis of a "basaloid neoplasm with slight atypia, favor basal cell adenoma" was made. The lesion was subsequently surgically excised by parotidectomy and revealed a neoplasm with histomorphologic features of the solid subtype of basal cell adenoma but with infiltration into parotid parenchyma and extra-glandular soft tissue, focal perineural invasion, and rare mitotic activity. Therefore, a diagnosis of "basal cell adenocarcinoma, solid subtype" was made. The patient has subsequently been free of disease for 5 years. Section 4 - Figure 1 Section 4 - Figure 2 Discussion: Basal cell adenoma and adenocarcinoma of the parotid gland Basal cell adenocarcinoma (BCAC) is a rare salivary gland neoplasm that is the malignant counterpart of basal cell adenoma (BCA). It should be considered in the differential diagnosis of any basaloid salivary gland neoplasm. BCAC is a low-grade malignancy with a good prognosis having a tendency for local recurrence, but metastatic disease is uncommon. BCAC accounts for 2% of malignant epithelial salivary gland tumors and 1.6% of all salivary gland neoplasms. Most cases occur in the parotid gland although occasional cases have been reported in the submandibular gland and the minor salivary glands. The average age at diagnosis is 60 years with an age range of 27 –92 years, and no sex predilection. Salivary gland enlargement is the main presenting symptom, and uncommonly pain or tenderness may also be present. Importantly, BCAC may be virtually identical to BCA based upon its cytomorphologic features; it is distinguished from the latter histologically by an infiltrative growth pattern. Although most cases have minimal cytologic atypia, there is a subset of BCAC that shows nuclear atypia, mitotic activity, and/or necrosis, and is therefore more easily recognized both cytologically and histologically as malignant. In general, BCAC and BCA cannot be distinguished on the basis of cytologic features. The cytologic diagnosis of BCAC and BCA rests on identifying two populations of basaloid cells: a group of small round to oval cells with bland hyperchromatic nuclei and scant cytoplasm, and a group of larger oval to polygonal or elongate cells with pale nuclei and delicate cytoplasm. The cells are arranged in variable-sized clusters or trabeculae sometimes with peripheral palisading of the smaller basaloid cells. Many cell groups may show a peripheral band of hyaline material as well as intercellular hyaline matrix that is not fibrillar (as in pleomorphic adenoma), and even smooth contoured hyaline globules may be present. The matrix material stains brightly cyanophilic or eosinophilic by Pap stain and basophilic to metachromatic by Diff-Quick. Some cases may contain cells with squamous differentiation. The cytomorphologic pattern will vary depending upon the subtype of BCAC (solid, tubulotrabecular, and membranous) encountered. The solid and tubulotrabecular patterns have overlapping cytologic features that may be difficult to reliably distinguish in aspirates, but the membranous type does have a distinctive cytologic pattern of cohesive cell groups with thick circumferential hyaline bands. Cytologic features of basal cell adenomoa/adenocarcinoma: Two populations of cytologically bland basaloid cells Solid, tubulotrabecular, and membranous patterns Peripheral palisading Squamous morules Acellular matrix material as peripheral bands around groups, and as small intercellular globules. Histologic Features of Basal Cell Adenoma/Adenocarcinoma: Histologically, BCAC is characterized by cohesive islands comprised of large and small basaloid cells, often with some degree of palisading at the periphery of groups. Variable amounts of hyalinized basal lamina may be seen either as intercellular droplets or as perinodular bands. Like BCA, BCAC has several morphologic growth patterns including solid, tubular/trabecular, and membranous, of which the solid pattern is the most common. The membranous subtype (AKA dermal analogue subtype) may be associated with multiple dermal cylindromas. Section 4 - Figure 3 Basal cell adenocarcinoma, solid type, showing peripheral small dark-staining basaloid cells, and more central larger basaloid cells . Infiltration into surrounding parenchyma and perineural invasion were present in this case. Section 4 - Figure 4 FNA of membranous BCA Differential Diagnosis The differential diagnosis of BCAC includes BCA, adenoid cystic carcinoma (ACC), metastatic basal cell carcinoma, and rarely, cellular pleomorphic adenoma or chronic sialadenitis (see Table). It has been suggested that the cytologic distinction of basaloid neoplasms, particularly the distinction of basal cell adenoma/adenocarcinoma from the solid variant of adenoid cystic carcinoma, may be the single most difficult diagnostic problem in the salivary gland! Pleomorphic adenoma is typically distinguished from both BCA & BCAC by its numerous cytologically bland myoepithelial cells as well as by the nature of its metachromatic chondromyxoid matrix material that is more often fibrillar with feathery outlines rather than hyalinized with smooth contours. One of the most important entities to exclude from the differential diagnosis is adenoid cystic carcinoma because of its more aggressive clinical behavior (indolent but with a poor long term prognosis). Differentiation of BCA & BCAC from typical cribriform and tubular forms of adenoid cystic carcinoma that exhibit three-dimensional and branching globules and cylinders of hyaline matrix material surrounded by small basaloid cells is usually much less difficult than differentiation from the solid form of adenoid cystic carcinoma. Cytologic features favoring BCA or BCAC over adenoid cystic carcinoma include: two easily identifiable populations of basaloid cells, hyaline-type matrix material between cells and surrounding groups of cells, peripheral palisading of cells, tinctorial properties of the matrix material (more intense in Pap-stained smears and more basophilic in Diff-Quik smears), oval to elongate rather than angulated nuclei, the presence of squamous differentiation, and the absence of nerve palsy. This being said, some cases of solid ACC may be virtually impossible to distinguish from BCA & BCAC. Cytologic Differential Diagnosis of Basaloid Tumors Cytologic Features BCAC* BCA** Pleomorphic Adenoma Adenoid Cystic Carcinoma Basal Cell Carcinoma Architecture cohesive clusters;+ peripheral palisading; haphazard cell arrangement cohesive clusters;+ peripheral palisading; haphazard cell arrangement sheets and syncytia with trabecular or ductal arrangement 3-D cylinders and branching groups; regular mosaic cell arrangement crowded tightly cohesive syncytial groups with sharp angular outlines;+ palisading Cells 2 basaloid cell types: Small hyperchromatic cells and larger pale cells 2 basaloid cell types: Small hyperchromatic cells and larger pale cells plasmacytoid & spindled myoepithelial cells and cuboidal epithelial cells basaloid cells and variable numbers of myoepithelial cells single population of basaloid cells with scant cytoplasm; rare keratin pearls Nuclei round to oval or elongate; +atypia; + mitotic activity round to oval or elongate; atypia and mitotic activity are absent or minimal round to oval with fine chromatin; absent or minimal atypia oval to angulated; mild to moderate atypia; + mitotic activity minimal to marked nuclear atypia; mitotic activity Stroma Intercellular hyaline matrix; circumferential hyaline bands; cyanophilic on Pap, metachromatic on Diff-Quick Intercellular hyaline matrix;circumferential hyaline bands; cyanophilic on Pap, metachromatic on Diff-Quick Fibrillar chondromyxoid matrix that is metachromatic on Diff-Quick; embedded cells large acellular cylinders and globules of hyaline matrix surrounded by cells; pale to transparent on Pap; metachromatic on Diff-Quick ; absent in solid type small amounts of intercellular fibrillary metachromatic matrix material Background naked nuclei;+ necrosis naked nuclei myoepithelial cells + necrosis necrosis * Basal cell adenocarcinoma; ** Basal cell adenoma