Recurrent IDH2 Mutations in Salivary Gland Striated Duct Adenoma Define an Expanded Histologic Spectrum Distinct From Canalicular Adenoma.

Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases.

Human Papillomavirus-Associated Oropharyngeal High-Grade Neuroendocrine Carcinoma in an Adolescent: Case Report and Review of Literature.

Oropharyngeal small cell carcinomas (OPSmCC) are rare with only few case reports and case series published in the literature. More recently, an association of these tumors with human papillomavirus (HPV) infection has been detected. However, unlike oropharyngeal squamous cell carcinomas which have a better outcome when associated with HPV, OPSmCC exhibit an aggressive behavior.

Recurrent RET Gene Rearrangements in Intraductal Carcinomas of Salivary Gland.

Intraductal carcinoma (IC) is the World Health Organization designation for lesions previously called low-grade cribriform cystadenocarcinoma. The relationship of IC to salivary duct carcinoma (SDC) is controversial, but currently these are considered distinct entities. It is hypothesized that IC and SDC should have different genomic signatures that may be identifiable by next-generation sequencing.

Epithelial-Myoepithelial Carcinoma: Frequent Morphologic and Molecular Evidence of Preexisting Pleomorphic Adenoma, Common HRAS Mutations in PLAG1-intact and HMGA2-intact Cases, and Occasional TP53, FBXW7, and SMARCB1 Alterations in High-grade Cases.

We hypothesized that there is a relationship between the preexisting pleomorphic adenoma [PA]), histologic grade of epithelial-myoepithelial carcinomas (EMCAs), and genetic alterations. EMCAs (n=39) were analyzed for morphologic and molecular evidence of preexisting PA (PLAG1, HMGA2 status by fluorescence in situ hybridization, FISH, and FGFR1-PLAG1 fusion by next-generation sequencing, NGS). Twenty-three EMCAs were further analyzed by NGS for mutations and copy number variation in 50 cancer-related genes.

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).

Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands.

Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.

Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin.

Polymorphous low-grade adenocarcinoma (PLGA) and cribriform adenocarcinoma of minor salivary gland (CAMSG) are low-grade carcinomas arising most often in oral cavity and oropharynx, respectively. Controversy exists as to whether these tumors represent separate entities or variants of one spectrum, as they appear to have significant overlap, but also clinicopathologic differences. As many salivary carcinomas harbor recurrent translocations, paired-end RNA sequencing and FusionSeq data analysis was applied for novel fusion discovery on two CAMSGs and two PLGAs.

Salivary duct carcinoma and the concept of early carcinoma ex pleomorphic adenoma.

Aims: The data on the histological type of carcinomatous component and the extent of extracapsular invasion for salivary carcinomas ex pleomorphic adenoma (PA) are conflicting. We aimed to determine the prognostic value of extracapsular invasion in salivary duct carcinomas (SDC) ex PA.

Methods And Results: A total of 117 patients with SDC were identified retrospectively; 44 cases involving major salivary glands had pre-existing PA (44 of 117, 37%).

Human papillomavirus and Epstein-Barr virus in nasopharyngeal carcinoma in a low-incidence population.

Background: The significance of human papillomavirus (HPV) in nasopharyngeal carcinomas (NPCs) in a low-incidence population remains unknown.

Methods: Samples from 90 patients with NPC (years, 1957-2012) were analyzed for Epstein-Barr virus (EBV). Clinical data, EBV, HPV, and p16 status were correlated with overall survival (OS; 63 cases; years, 1981-2012).

Use of anti tumor necrosis factor-alpha monoclonal antibody for ulcerative jejunoileitis.

Ulcerative jejunoileitis is an uncommon clinical syndrome consisting of abdominal pain, weight loss associated with diarrhea, and multiple inflammatory ulcerations and strictures of the small bowel. Ulcerative jejunoileitis can complicate established celiac disease or develop in patients de novo. Increased levels of tumor necrosis factor-alpha (TNF-α) in the small intestine of patients with untreated celiac disease are associated with a role in the immune pathogenesis of this disorder.

Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands.

Aims: Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC.

Methods And Results: Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented.

The profile of acinic cell carcinoma after recognition of mammary analog secretory carcinoma.

To determine the influence of the newly described mammary analog secretory carcinoma (MASC) with ETV6 translocation on our understanding of salivary acinic cell carcinoma (AciCC), we reviewed 81 cases of AciCC: 64 "classic" AciCCs, 11 AciCCs with high-grade transformation (HGT), and 17 zymogen granule poor AciCCs. ETV6 fluorescence in situ hybridization revealed that classic AciCC (7 of 7 tested) and AciCC-HGT (4 of 4 tested) have intact ETV6. However, 10 of 17 zymogen granule poor AciCCs showed ETV6 translocation and were reclassified as MASC; the diagnosis of AciCC was retained for cases with intact ETV6.

Multiple tumor-suppressor genes on chromosome 3p contribute to head and neck squamous cell carcinoma tumorigenesis.

Head and neck squamous cell carcinoma (HNSCC) remains a significant cause of morbidity and mortality. There has been a great interest in finding specific genomic changes which contribute to HNSCC tumorigenesis, especially within the chromosome 3p area, where high frequency of LOH (loss of heterozygosity) has been reported. However, tumor-suppressor genes that may account for the frequent LOH remain to be identified.

The T1799A BRAF mutation is absent in cribriform-morular variant of papillary carcinoma.

Context: Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) is one of the rare types of papillary carcinoma. It has been associated with familial adenomatous polyposis, though it can also occur sporadically. The molecular pathogenesis of this tumor is incompletely understood.

Head and neck squamous cell carcinoma in FAMMM syndrome.

Background: Germline mutations at the INK4a/p16 locus are implicated in several human cancer syndromes, including familial atypical multiple mole melanoma (FAMMM) syndrome, FAMMM-pancreatic cancer (FAMMM-PC) syndrome, and in familial head and neck cancer syndrome.

Methods: We present an individual with a family history of melanoma and pancreatic cancer who had multiple dysplastic nevi, squamous cell carcinoma of the tongue at age 22, multiple melanomas, a second squamous cell cancer of the tongue at age 40, and ultimately a pancreatic cancer.

Results: We demonstrate a germline mutation in INK4a and loss of heterozygosity at this locus in his HNSCC tissue.

Invasive size is an independent predictor of survival in pulmonary adenocarcinoma.

Current classification of pulmonary adenocarcinoma includes noninvasive bronchioloalveolar carcinoma, mixed subtype adenocarcinoma, and several patterns of invasive carcinoma. The extent of invasion in mixed subtype adenocarcinoma is variable, and prior studies suggest that estimates of extent of desmoplasia or invasion and gross tumor size are predictors of survival. Pathologic review of 178 consecutive primary lung adenocarcinoma resections from 1997 to 2000 was performed blinded to outcome.

Thyroidectomies from patients with history of therapeutic radiation during childhood and adolescence have a unique mutational profile.

Radiation in childhood is a known risk factor for thyroid carcinoma, but may also be related to benign nodular hyperplasias. Recent evidence from comparative genomic hybridization indicates that radiation can induce clonal DNA damage in cultured rat thyrocytes. We used a loss of heterozygosity analysis for the loci identified by comparative genomic hybridization to study human thyroids.

Novel mutant-enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer.

We previously reported 4 PIK3CA mutations in 38 head and neck cancer samples, 3 of which were identified in 6 pharyngeal cancer samples. To determine the mutation frequency of PIK3CA in pharyngeal cancer, we studied 24 additional cases of pharyngeal squamous cell carcinoma in this study. Using both direct genomic DNA sequencing and novel mutant-enriched sequencing methods developed specifically for the 3 hot-spot mutations (H1047R, E545K and E452K) of PIK3CA, we detected 5 mutations of PIK3CA in the 24 pharyngeal cancers (20.

Platelet-derived growth factor is increased in pulmonary capillary hemangiomatosis.

Background: Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown.

Methods: We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects.

Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma.

Immunohistochemical staining for cytokeratin 7 (CK7), KIT, and PAX2 expression was performed on 91 renal neoplasms, 37 conventional (clear cell) renal cell carcinomas (CRCCs), 20 papillary RCCs (PRCCs), 11 chromophobe RCCs (ChCs), and 23 oncocytomas, with available karyotypes. All ChCs, 19 PRCCs, 2 CRCCs, and 1 oncocytoma were CK7+; all ChCs, 22 oncocytomas, 2 CRCCs, and no PRCCs expressed KIT; PAX2 was positive in 31 CRCCs, 17 PRCCs, 20 oncocytomas, and 1 ChC. The predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37); PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7-/KIT+/PAX2+ (19/23).

Branchial cleftlike cysts of the thyroid.

Branchial cleftlike cysts of the thyroid gland are rare lesions. Although initially described in patients with chronic lymphocytic thyroiditis, these cysts have been reported in a variety of histologic settings. We present 2 case studies, 1 in a 30-year-old woman and 1 in a 50-year-old man.

Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors.

Background: Male germ cell tumor (GCT) is a highly curable malignancy, which exhibits exquisite sensitivity to cisplatin treatment. The genetic pathway(s) that determine the chemotherapy sensitivity in GCT remain largely unknown.

Results: We studied epigenetic changes in relation to cisplatin response by examining promoter hypermethylation in a cohort of resistant and sensitive GCTs.