We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.
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"The distinction is important since it is not only histologic, but also clinical, prognostic, and with therapeutic implications as well . The distinct features of the PDCs remained somewhat unclear for years, after the original description of this entity  as different histopathological tumor types were combined under this term by different authors         . "
[Show abstract][Hide abstract] ABSTRACT: Histological and cytological criteria in predicting clinical outcomes in patients with oncocytic poorly differentiated carcinoma (PDC) of the thyroid were investigated. In a set of 102 PDC patients, we performed a computer-assisted evaluation of cell size based on two different methods. Univariate analysis showed that cell size was a discriminant prognostic parameter in oncocytic PDC (30 cases) but not in the non-oncocytic carcinomas cases (72 cases). Patients with oncocytic PDC with small medium cell size had a significantly increased risk of death (p=0.029) and a decrease of disease-free survival (p=0.014). This correlation was absented in cases of non-oncocytic PTC, where age and extensive vascular invasion were significant indicators of progression. The proposed morphological signature shows a robust discriminatory ability when tested on the oncocytic PDC group and cell size assessment could thus be proposed as an inexpensive and readily evaluable parameter for predicting prognosis and planning therapy in this tumor type.
"They appear partially de-differentiated compared to FTCs or PTCs and typically behave more aggressively . Several of these tumors arise de novo, whereas others seem to originate from PTCs or FTCs . "
[Show abstract][Hide abstract] ABSTRACT: Thyroid cancer is one of the most common malignancies of the endocrine system with increasing incidence. The vast majority of thyroid carcinomas derive from thyroid hormone producing follicular cells. Carcinomas of follicular origin are classified as follicular (FTCs), papillary (PTCs), partially differentiated (PDTCs) or anaplastic (ATCs) thyroid carcinomas. While FTCs and PTCs can be managed effectively, ATCs are considered one of the most lethal human cancers. Despite the identification of various genetic alterations, pathogenic mechanisms promoting the progression of thyroid carcinomas are still largely elusive. Over the recent years, aberrant microRNA expression was revealed in all as yet analyzed human cancers, including thyroid carcinomas. In view of the rapidly evolving perception that deregulated microRNA expression serves a pivotal role in tumor progression, microRNAs provide powerful tools for the diagnosis of thyroid carcinomas as well as the identification of potential therapeutic targets. Here, we summarize recent findings on microRNA signatures in thyroid carcinomas of follicular origin and discuss how deregulated microRNA expression could promote cancer progression.
[Show abstract][Hide abstract] ABSTRACT: Some of the numerous examples that can be quoted are those on dysplasia in Barrett's esophagus, 6 grading of prostatic carcinoma, 7 grading of breast carcinoma, 8 diagnosis of hydatidiform mole, 9 and classification of thymic tumors. 10 On first sight, these results make surgical pathology look like a subjective, arbitrary, unscientific discipline, and therefore many surgical pathologists don't like them. I still get occasional snotty remarks about a study of the kind I did many years ago on proliferative ductal lesions of the breast. 11 Yet, I doubt whether burying our head in the sand is the solution. Perhaps it is the nature of the beast, and nothing can be done about it. 12 As Vickery 13 stated, some of the criteria on which we base those distinctions "may be indefinite and vulnerable to subjective morphologic interpretation." Or perhaps some of these studies will identify a specific problem that can be addressed. The various thyroid studies above quoted mainly deal with the diagnostic significance of certain morphologic nuclear features (herein referred to as PTC-type nuclei) in the diagnosis of papillary thyroid carcinoma (PTC). It is obvious from the results obtained that some experts have a much lower threshold for the identification and/or diagnostic significance of PTC-type nuclei than others. It may be of some interest to briefly recount the evolution that PTC-type nuclei have had in thyroid pathology until reaching their presently exalted status. Originally, and for the many decades that followed its description, PTC was diagnosed primarily on the basis of the presence of papillae, hence its name. Then people began noticing that these tumors had peculiar nuclei, which looked empty or optically clear. Ronald DeLellis 14 gave credit to Nancy Warner for drawing the amusing analogy between these nuclei and the eyes of Harold Gray's comic strip character, "Little Orphan Annie". Thus, the expression "Orphan Annie's eyes nuclei" became popular when referring to PTC, although the presence of papillae and other cytoarchitectural features (carefully listed and discussed in Vickery's authoritative review on the subject 13 ) were still regarded as important criteria for the diagnosis of PTC. However, with the passing of the years, PTC-type nuclei rose through the ranks, so to speak, to become the paramount criterion for the diagnosis of PTC. At present, a thyroid tumor can have a papillary, follicular, solid, trabecular or cribriform pattern of growth; it can be composed of large, small, oncocytic, clear, round, spindle or columnar cells; it can be encapsulated, minimally invasive or widely invasive; in sum, it can have any of those features and more, but as long as it has PTC-type nuclei it is thought to be a PTC or one of its innumerable variants.