Paul E. Wakely

Modulation of Sodium/Iodide Symporter Expression in the Salivary Gland

BACKGROUNDnPhysiologic iodide-uptake, mediated by the sodium/iodide symporter (NIS), in the salivary gland confers its susceptibility to radioactive iodine-induced damage following (131)I treatment of thyroid cancer. Subsequent quality of life for thyroid cancer survivors can be decreased due to recurrent sialoadenitis and persistent xerostomia. NIS expression at the three principal salivary duct components in various pathological conditions was examined to better our understanding of NIS modulation in the salivary gland.nnnMETHODSnNIS expression was evaluated by immunohistochemistry in human salivary gland tissue microarrays constructed of normal, inflamed, and neoplastic salivary tissue cores. Cumulative (123)I radioactivity reflecting the combination of NIS activity with clearance of saliva secretion in submandibular and parotid salivary glands was evaluated by single-photon emission computed tomography/computed tomography imaging 24 hours after (123)I administration in 50 thyroid cancer patients.nnnRESULTSnNIS is highly expressed in the basolateral membranes of the majority of striated ducts, yet weakly expressed in few intercalated and excretory duct cells. The ratio of (123)I accumulation between parotid and submandibular glands is 2.38±0.19. However, the corresponding ratio of (123)I accumulation normalized by volume of interest is 1.19±0.06. The percentage of NIS-positive striated duct cells in submandibular salivary glands was statistically greater than in parotid salivary glands, suggesting a higher clearance rate of saliva secretion in submandibular salivary glands. NIS expression in striated ducts was heterogeneously decreased or absent in sialoadenitis. Most ductal salivary gland tumors did not express NIS. However, Warthins tumors of striated duct origin exhibited consistent and intense NIS staining, corresponding with radioactive iodine uptake.nnnCONCLUSIONSnNIS expression is tightly modulated during the transition of intercalated to striated ducts and striated to excretory ducts in salivary ductal cells. NIS expression in salivary glands is decreased during inflammation and tumor formation. Further investigation may identify molecular targets and/or pharmacologic agents that allow selective inhibition of NIS expression/activity in salivary glands during radioactive iodine treatment.

Surgical management of oropharyngeal squamous cell carcinoma: Survival and functional outcomes

The purpose of this study was to further define the impact of primary surgery in the management of oropharyngeal squamous cell carcinoma (SCC).

Highly aggressive human papillomavirus-related oropharyngeal cancer: clinical, radiologic, and pathologic characteristics

OBJECTIVEnAlthough the majority of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas have a favorable prognosis, we search for markers of poor prognosis by carefully examining a subset of highly aggressive cases.nnnSTUDY DESIGNnSeven patients with HPV-positive oropharyngeal cancer who presented with non-pulmonary distant metastasis or developed distant metastasis posttreatment were identified. Eight control cases were chosen which responded well to treatment. Pathologic and radiologic studies were reviewed and compared.nnnRESULTSnTwo cases displayed a small cell carcinoma (SmCC) component upon pathologic review. Biomarker analysis revealed lower expression of NOTCH1 in the aggressive cohort in comparison to controls (P = .04). Cases showed a predominance of clustering of lymph nodes, extracapsular spread, and central tumor necrosis.nnnCONCLUSIONnAlthough most HPV-related oropharyngeal cancers display a positive prognosis, it is evident that there is a subset, which behaves more aggressively. This early investigation identifies pathologic and radiologic features that may help to predict this behavior.

Nuclear PRMT5, cyclin D1 and IL-6 are associated with poor outcome in oropharyngeal squamous cell carcinoma patients and is inversely associated with p16-status

Protein arginine methyltransferase-5 (PRMT5) plays an important role in cancer progression by repressing the expression of key tumor suppressor genes via the methylation of transcriptional factors and chromatin-associated proteins. However, very little is known about the expression and biological role of PRMT5 in head and neck cancer. In this study, we examined expression profile of PRMT5 at subcellular levels in oropharyngeal squamous cell carcinoma (OPSCC) and assessed its correlation with disease progression and patient outcome. Our results show that nuclear PRMT5 was associated with poor overall survival (p < 0.012) and these patients had 1.732 times higher hazard of death (95% CI: 1.127–2.661) as compared to patients in whom PRMT5 was not present in the nucleus of the tumors. Nuclear PRMT5 expression was inversely correlated with p16-status (p < 0.001) and was significantly higher in tumor samples from patients who smoked > 10 pack-years (p = 0.013). In addition, nuclear PRMT5 was directly correlated with cyclin D1 (p = 0.0101) and IL-6 expression (p < 0.001). In a subgroup survival analysis, nuclear PRMT5-positive/IL-6-positive group had worst survival, whereas nuclear PRMT5-negative/IL-6-negative group had the best survival. Similarly, patients with p16-negative/nuclear PRMT5-positive tumors had worse survival compared to patients with p16-positive/nuclear PRMT5-negative tumors. Our mechanistic results suggest that IL-6 promotes nuclear translocation of PRMT5. Taken together, our results demonstrate for the first time that nuclear PRMT5 expression is associated with poor clinical outcome in OPSCC patients and IL-6 plays a role in the nuclear translocation of PRMT5.

Silverberg's principles and practice of surgical pathology and cytopathology

Interestingly, principles and practice of surgical pathology and cytopathology that you really wait for now is coming. Its significant to wait for the representative and beneficial books to read. Every book that is provided in better way and utterance will be expected by many peoples. Even you are a good reader or not, feeling to read this book will always appear when you find it. But, when you feel hard to find it as yours, what to do? Borrow to your friends and dont know when to give back it to her or him.

Nodular fasciitis: A frequent diagnostic pitfall on fine-needle aspiration.

Nodular fasciitis (NF) is a benign, self‐limited, fibroblastic/myofibroblastic proliferation that is diagnostically challenging, often mimicking a malignant process due to its rapid growth clinically and its high cellularity, mitotic activity, and variable/nonspecific cytomorphologic findings. Herein, the authors report what to their knowledge is the largest and first multi‐institutional study of the cytomorphologic characteristics of NF by fine‐needle aspiration (FNA).

Sinonasal Tract Alveolar Rhabdomyosarcoma in Adults: A Clinicopathologic and Immunophenotypic Study of Fifty-Two Cases with Emphasis on Epithelial Immunoreactivity

Sinonasal tract (SNT) alveolar rhabdomyosarcoma (ARMS) are frequently misdiagnosed, especially in adults. Fifty-two adult (≥18xa0years) patients with SNT ARMS were reviewed and characterized by immunohistochemistry and molecular studies. Twenty-six females and 26 males (18–72xa0years; mean 43.2xa0years), presented after a short duration (mean 2.6xa0months) with a large (mean 5.5xa0cm) destructive nasalxa0cavity mass, involving multiple contiguous paranasal sites (nu2009=u200946) and with cervical adenopathy (nu2009=u200941). The tumors showed an alveolar, nested to solid growth pattern below an intact, but often involved (nu2009=u20099) epithelium with frequent necrosis (nu2009=u200937), destructive bone invasion (nu2009=u200930), and lymphovascular invasion (nu2009=u200925). The neoplastic cells were dyshesive and dilapidated, with crush artifacts. Rhabdoid features (nu2009=u200936) and tumor cell multinucleation (nu2009=u200928) were common. Mitotic counts were high (mean 17/10 HPFs). The neoplastic cells showed the following immunohistochemical positive findings: desmin (100%), myogenin (100%), MYOD1 (100%), MSA (96%), SMA (52%), CAM5.2 (50%), AE1/AE3 (36%); other positive markers included S100 protein (27%), CD56 (100%), synaptophysin (35%), and chromogranin (13%). Overall, 54% show epithelial marker reactivity. Molecular studies showed FOXO1 translocations (81%) with PCR demonstrating PAX3 in 72.7% tested. Patients presented with high stage (IV 24; III 26) and metastatic disease (lymph nodes nu2009=u200941; distant metastases nu2009=u200925) (IRSG grouping). Surgery (nu2009=u200916), radiation (nu2009=u200941) and chemotherapy (nu2009=u200945) yielded an overall survival of 36.1 months (mean; range 2.4–286); 18 alive without disease (mean 69.6 months); 7 alive with disease (mean 11.0 months); 1 dead without disease (63.7 months); and 26 dead with disease (mean 18.5 months). SNT ARMS frequently present in adults as a large, destructive midline mass of short symptom duration, with high stage disease. The alveolar to solid pattern of growth of cells with rhabdoid-plasmacytoid features suggests the diagnosis, but epithelial immunohistochemistry markers are present in 54% of cases, leading to misdiagnosis as carcinomas if muscle markers are not also performed. Overall survival of 36.1 months is achieved with multimodality therapy, but 64% have incurable disease (16.9 months). Mixed anatomic site (pu2009=u20090.02) was a significant adverse prognostic indicator, while stage (0.06) and tumor size >5xa0cm (0.06) approached marginal significance.

Chondroblastic osteosarcoma: Cytomorphologic characteristics and differential diagnosis on FNA.

Chondroblastic osteosarcoma (COS) is a uniformly fatal bone malignancy if not diagnosed and treated appropriately in a timely manner. Fine‐needle aspiration (FNA) of osseous lesions is routinely performed in major medical centers. Appropriate characterization of the tumor will significantly influence patient management and outcomes.

Primary gastric extra-uterine endometrial stromal sarcoma.

Endometrial stromal sarcoma (ESS) is an uncommon uterine neoplasm, but its occurrence as an extra-uterine primary (EESS) is exceedingly unusual, and the fine-needle aspiration (FNA) cytopathology of EESS is rarely described. We hereby present 2 women with primary gastric EESS whereby the FNA cytopathology of this rare entity showed a population of cytologically monotonous oval-spindle shaped cells. This cytopathology is correlated with the subsequent histopathology. EESS is another, albeit rare, diagnostic consideration along with gastrointestinal stromal tumor, schwannoma, glomus tumor, and leiomyoma of cytologically bland neoplasms of the stomach that can be encountered using endoscopic ultrasound-guided FNA biopsy.

Variants in microRNA genes in familial papillary thyroid carcinoma

Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs’ maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common.