Thyroid neoplasms of follicular cell derivation: A simplified approach

Thyroid tumors of follicular cell derivation are increasing in incidence. These lesions exhibit a spectrum of morphologic and behavioral features that provide the opportunity to understand malignant transformation and progression. Molecular data suggest that the thyroid undergoes a series of genetic alterations that account for the development of the various types of thyroid carcinoma. Our understanding of these tumors has progressed dramatically over the past 50 years and the classification has become complex and cumbersome. We provide a practical approach to clinical diagnosis and propose a simplified classification of these common neoplasms.     

Comparison of diagnostic values of thyroid aspiration samples using liquid‐based preparation and conventional smear: one‐year experience in a single institution

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Fine‐needle aspiration (FNA) is the most useful tool in the diagnosis of thyroid nodules. Liquid‐based preparation (LBP) in FNA of thyroid nodules is now widely used and is replacing the conventional smear (CS). We compared the diagnostic value of the LBP method with that of CS in thyroid lesions. A total of 1767 CS FNA samples and 2523 LBP FNA samples were included in this comparison of diagnostic values. We also assessed the differences in cytomorphologic features in 41 randomly selected cases of PTC. The measured sensitivities of CS and LBP were 78.9% and 76.3%, respectively, and the specificities were 64.2% and 54.9%, respectively, whereas the positive predictive values were 92.3% and 94.3%, respectively, and the negative predictive values were 89.5% and 81.8%, respectively. The cytomorphological features of LBP showed better‐preserved nuclear details, cleaner background and fewer large papillae than were evident in CS. The results indicate that LBP reduces the diagnosis of non‐diagnostic or unsatisfactory/atypia of undetermined significance or follicular lesion of undetermined significance, although the diagnostic values for CS and LBP are not appreciably different.     

Do HOXB13 and P63 have a role in differentiating poorly differentiated prostatic carcinoma from urothelial high‐grade carcinoma?

Poorly differentiated prostatic carcinoma may overlap with high‐grade urothelial carcinoma; a distinction is a must as treatments differ. This study aims to evaluate traditional (PSA and HMWCK) and relatively novel (P63 and HOXB13) markers in distinguishing them; and to evaluate their role in the diagnosis of challenging cases. Sections from: diagnosed group includes 65 prostatic and urothelial carcinoma cases were stained with PSA, HMWCK, P63, and HOXB13. Sensitivity, specificity, and accuracy were evaluated. The second group includes 25 challenging cases which were stained first by PSA and HMWCK, then solved the problematic cases with P63 and HOXB13. PSA and HMWCK were sensitive and specific for prostatic and urothelial carcinomas, respectively, but the sensitivity and accuracy were higher for P63 and HOXB13. By using the traditional markers, 17 cases were diagnosed in the second group while the remaining eight cases need the novel markers to be diagnosed. A confident diagnosis can be established in the majority of cases of poorly differentiated carcinoma in either prostatic or urothelial by using a panel of PSA and HMWCK. In some problematic cases, an extended panel including P63 and HOXB13 is helpful in resolving the diagnosis.     

Multiple and bilateral kidney tumors with clear cells of three different histotypes: A case report with clinicopathologic and molecular study

We describe a rare multicentric neoplastic disease arising bilteraly in the kidney. The patient was a 70‐year‐old man, who, during a period of 3 years, was treated for five independent tumors of three histotypes (three multilocular cystic clear cell renal cell neoplasms of low malignant potential, one clear cell renal cell carcinoma, and one clear cell papillary renal cell carcinoma, respectively). Pathologic diagnosis of the reported tumors was confirmed by immunohistochemical analyses, including CD10, CA IX, CK7, AMACR/RACEMASE, and 34 beta E12. Molecular detection of KRAS, BRAF, NRAS, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET, and EGFR gene mutational analysis was also performed in all tumors.     

TESTIN was commonly hypermethylated and involved in the epithelial‐mesenchymal transition of endometrial cancer

We previously reported frequent loss of TESTIN in human endometrial carcinoma, which significantly suppressed tumor proliferation and invasion. Herein, we further explored the mechanisms underlying TESTIN loss and its roles in the epithelial‐mesenchymal transition (EMT, a key step for tumor spreading). Methylation‐specific PCR was performed to investigate the promoter status of TESTIN in a panel of endometrial cancer and normal endometrium tissues. The expression of TESTIN mRNA was determined by real‐time PCR. Up‐ and down‐regulation of TESTIN were achieved by transient transfection with pcDNA3.1‐TESTIN and shRNA‐TESTIN plasmids, respectively. The EMT alterations were observed under the optical microscope and EMT‐related markers were detected by real‐time PCR and western blot. Compared to the control (3.6%), TESTIN was hypermethylated in 43.7% endometrial cancer tissues (p < 0.001). Moreover, TESTIN hypermethylation was significantly correlated with advanced tumor stage, deep myometrial invasion and lymphatic node metastasis. In vitro, the demethylating agent dramatically restored the expression of TESTIN. In addition, up‐regulation of TESTIN significantly suppressed the EMT procedure; whereas down‐regulation of TESTIN enhanced EMT. In conclusion, we demonstrated that loss of TESTIN was mainly caused by hypermethylation, which might be a potent prognostic marker. Furthermore, we proved that TESTIN significantly suppressed the EMT procedure, proposing restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma.     

Molecular pathology of thyroid tumours of follicular cells: a review of genetic alterations and their clinicopathological relevance

Thyroid cancer is the most common endocrine malignancy. Knowledge of the molecular pathology of thyroid tumours originating from follicular cells has greatly advanced in the past several years. Common molecular alterations, such as BRAF p.V600E, RAS point mutations, and fusion oncogenes (RET–PTC being the prototypical example), have been, respectively, associated with conventional papillary carcinoma, follicular‐patterned tumours (follicular adenoma, follicular carcinoma, and the follicular variant of papillary carcinoma/non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features), and with papillary carcinomas from young patients and arising after exposure to ionising radiation, respectively. The remarkable correlation between genotype and phenotype shows how specific, mutually exclusive molecular changes can promote tumour development and initiate a multistep tumorigenic process that is characterised by aberrant activation of mitogen‐activated protein kinase and phosphoinositide 3‐kinase–PTEN–AKT signalling. Molecular alterations are becoming useful biomarkers for diagnosis and risk stratification, and as potential treatment targets for aggressive forms of thyroid carcinoma. What follows is a review of the principal genetic alterations of thyroid tumours originating from follicular cells and of their clinicopathological relevance.