A spectrum of basaloid morphology in a subset of EBV-associated "lymphoepithelial carcinomas" of major salivary glands

Nasopharyngeal carcinomas of the undifferentiated or lymphoepithelial type are most commonly seen in South East Asians. Identical tumors have also been described at a variety of other sites including lung, skin and salivary gland and have been referred to by a number of names including lymphoepithelial carcinoma (LEC). LECs of major salivary gland are extremely rare. They are particularly common amongst the Inuit populations of the arctic region including Greenland (Denmark), Canada and Alaska, as well as South East Asians. Within the Inuit group, this tumor represents the majority of all salivary gland carcinomas. Amongst primary LEC of major salivary gland, most cases reported in the literature have represented typical nasopharynx-like tumors. Variants of Epstein–Barr Virus (EBV) associated LEC have not been described previously, to the best of our knowledge. In this report, we describe 4 EBV-associated major salivary gland LECs with prominent basaloid morphology, which represent 22 % of a cohort of 18 salivary LECs from an Inuit population in Greenland. The features described in these cases raise a differential diagnosis of other basaloid tumors, particularly in light of the salivary gland location. A basaloid variant of LEC in major salivary gland should be recognized, especially in highly prone populations, to avoid misdiagnosis of other more common salivary tumors

Microcribriform Adenocarcinoma of Salivary Glands: A Unique Tumor Entity Characterized by an SS18::ZBTB7A Fusion

The landscape of salivary gland carcinomas is ever-changing, with a growing list of new tumors and newly elucidated variants of well-known tumor entities. The routine use of next-generation sequencing has been instrumental in identifying novel fusions and tumor entities, which has helped bring the classification to a more objective and evidenced-based model. However, morphology remains critical in assessing the validity of these novel molecular findings, and most importantly, in assessing which of these findings will have an impact on the prognosis and treatment decisions for patients. The recognition of microsecretory adenocarcinoma (MSA) as a distinct low-grade malignancy of salivary glands, underpinned by MEF2C::SS18, and a single possibly related case of SS18::ZBTB7A, recently expanded this growing list of distinctive tumors. It was not until now, however, that the morphology of the latter case was known to be unique and reproducible. The authors have now seen 4 of these distinctive tumors that show a combination of distinctive oncocytic cells forming compact glandular growth as well as amphophilic cells forming tubular growth, and suggest the appellation "microcribriform adenocarcinoma" (MCA). So far, these tumors appear to preferentially occur in nonoral sites (2 parotid, 1 submandibular gland, and 1 bronchial seromucous glands). By immunohistochemistry, they express S100 and SOX-10 with focal outer myoepithelial cells marked by circumferential p63, p40, and smooth muscle actin staining around some of the nests and tubules. The tumors show infiltrative growth within a hyalinized and myxoid stroma. Cytologically, they appear generally low grade, similar to MSA. The morphologic and molecular uniformity of these 4 microcribriform adenocarcinoma cases warrants their recognition, and while related to MSA, they are sufficiently different to be classified as a distinct tumor. So far, in limited follow-up, these tumors appear to be relatively indolent

HPV-independent Vulvar Squamous Cell Carcinoma is Associated With Significantly Worse Prognosis Compared With HPV-associated Tumors

Vulvar squamous cell carcinomas (VSCC) represent the most common carcinoma of the female external genitalia, with increasing incidence. Although high-risk human papillomavirus (HPV) infection has long been implicated in the majority of cervical and anal squamous cell carcinomas, there is uncertainty about its prevalence and prognostic impact in VSCC. In this study, we conducted a retrospective integrated morphologic and multimodal HPV analysis of a cohort of 114 VSCC cases treated at the Princess Margaret Cancer Centre/University Health Network, Toronto, Canada between 2000 and 2010. VSCC histology was reviewed. We analyzed the cohort for HPV using polymerase chain reaction based method, and tissue microarray DNA and RNA in situ hybridization (ISH), and p16 immunohistochemistry. Among the 114 cases (age 70±16 yr), 36.7% of cases were classified as having histomorphology of HPV infection. HPV was detected in 31.9% (polymerase chain reaction), 14.0% (DNA ISH), and 27.3% (RNA ISH) of cases. p16 immunohistochemistry was positive in 37.8% of cases. On univariate analysis, HPV morphology (P=0.009), p16+ (P=0.00013), DNA ISH+ (P=0.021), and RNA ISH+ (P=0.00061) were associated with better 5-yr progression-free survival. DNA ISH+ (P=0.049) was associated with better 5-yr overall survival. On multivariate analysis, HPV morphology (P=0.033), p16+ (P=0.01), and RNA ISH+ (P=0.035) were associated with better 5-yr progression-free survival. In conclusion, a subset of VSCC is associated with HPV, which correlates with better outcome. Relatively inexpensive tests such as histomorphologic evaluation, p16 immunohistochemistry, and HPV RNA ISH can be used to predict outcome in VSCC. Therefore, routine reporting of HPV status in VSCC is recommended

Intraductal Carcinoma of Salivary Gland (So-Called Low-Grade Cribriform Cystadenocarcinoma) Arising in an Intraparotid Lymph Node

Since the first description of an entirely intraductal epithelial proliferation of salivary gland by Chen in 1983 as an “intraductal carcinoma”, there have been several dozen reported cases with the same and various additional names including “low-grade salivary duct carcinoma”, “low-grade cribriform cystadenocarcinoma” and “carcinoma in situ” of salivary gland. These refer to a combination of nests and cysts of varying size formed by a cellular proliferation resembling atypical ductal hyperplasia or ductal carcinoma in situ of the breast. The lesions are generally entirely intraductal with low, intermediate or high-grade dysplasia. Occasional benign tumors of salivary gland, particularly Warthin tumor and rare salivary carcinomas may arise within an intraparotid lymph node. In addition, intraparotid lymph nodes are a routine location for metastatic disease. A case of a 59-year-old female with a parotid mass is described, which grossly had the appearance of a Warthin tumor. Microscopically, it was an entirely intranodal proliferation of cells with diffuse AE1/AE3 and S100 positivity. The nests and cysts were completely surrounded by a rim of non-neoplastic myoepithelial cells, which were positive for CK14, p63, SMA, MSA and calponin. The tumor cells were negative for these markers. The cells were only focally positive for AR and BRST-2. They showed negligible MIB-1 staining. This report describes, for the first time, an entirely intranodal location for a low-grade intraductal carcinoma (so-called low-grade cribriform cystadenocarcinoma)

Salivary duct carcinoma: the predominance of apocrine morphology, prevalence of histologic variants, and androgen receptor expression

Salivary duct carcinoma (SDC) is a prototypic aggressive salivary gland carcinoma. Our aim is to determine the prevalence of histologic variants (micropapillary, basal-like) and androgen receptor (AR) expression in a large multi-institutional series of SDC. AR status was determined by immunohistochemistry (IHC). Most SDCs were characterized by an apocrine phenotype and AR expression. Cases with a nonapocrine phenotype and AR-negative status were studied by additional IHC and fluorescence in situ hybridization for ETV6 or MYB/NFIB. The diagnosis of SDC was confirmed in 187 of 199 (94%) cases. Variant morphologies were identified in 12 cases: micropapillary (n=6), sarcomatoid (n=3), mucinous (n=2), and basal-like (n=1). AR IHC was performed in 183 cases, of which 179 (97.8%) showed AR expression. On the basis of morphologic appearance and results of additional studies, 12 cases were reclassified as squamous cell carcinoma (SCC) (n=4), epithelial-myoepithelial carcinoma with high-grade transformation (HGT) (n=2), myoepithelial carcinoma (n=2), mammary analogue secretory carcinoma, high grade (ETV6 translocated; n=1), adenoid cystic carcinoma with HGT (n=1), acinic cell carcinoma with HGT (n=1), and adenosquamous carcinoma (n=1). AR-negative SDC is extremely rare, and the majority of such cases are more accurately classified as other entities. HGTs of other salivary carcinomas and squamous cell carcinoma are the most common mimics of SDC. SDCs with variant morphologies still show at least a minor component of conventional apocrine appearance. Thus, apocrine morphology defines SDC