Poorly differentiated (PD) thyroid carcinomas lie both morphologically and behaviorally between well-differentiated and undifferentiated (anaplastic) carcinomas. Following the original description of this entity, different diagnostic criteria have been employed, resulting in wide discrepancies and confusion among pathologists and clinicians worldwide. To compare lesions occurring in different geographic areas and the diagnostic criteria applied in those countries, we designed a study with a panel of internationally recognized thyroid pathologists to develop consensus diagnostic criteria for PD carcinomas. Eighty-three cases were collected from Europe, Japan, and the United States, and circulated among 12 thyroid pathologists. Diagnoses were made without any knowledge of the clinical parameters, which were subsequently used for survival analysis. A consensus meeting was then held in Turin, Italy, where an agreement was reached concerning the diagnostic criteria for PD carcinoma. These include (1) presence of a solid/trabecular/insular pattern of growth, (2) absence of the conventional nuclear features of papillary carcinoma, and (3) presence of at least one of the following features: convoluted nuclei; mitotic activity >or=3 x 10 HPF; and tumor necrosis. An algorithmic approach was devised for practical use in the diagnosis of this tumor.
We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.
In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.
We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.
Experimental evidence has shown , both in vitro and in animal models , that neoplastic growth and subsequent metastasis formation depend on the tumor's ability to induce an angiogenic switch. This requires a change in the balance of angiogenic stimulators and inhibitors. To assess the potential role of angiogenesis factors in human thyroid tumor growth and spread , we analyzed their expression by semiquantitative RT-PCR and immunohistochemistry in normal thyroid tissues , benign lesions , and different thyroid carcinomas. Compared to normal tissues , in thyroid neoplasias we observed a consistent increase in vascular endothelial growth factor (VEGF) , VEGF-C, and angiopoietin-2 and in their tyrosine kinase receptors KDR , Flt-4 , and Tek. In particular , we report the overexpression of angiopoietin-2 and VEGF in thyroid tumor progression from a prevascular to a vascular phase. In fact , we found a strong association between tumor size and high levels of VEGF and angiopoietin-2. Furthermore , our results show an increased expression of VEGF-C in lymph node invasive thyroid tumors and , on the other hand , a decrease of thrombospondin-1 , an angioinhibitory factor , in thyroid malignancies capable of hematic spread. These results suggest that , in human thyroid tumors , angiogenesis factors seem involved in neoplastic growth and aggressiveness. Moreover , our findings are in keeping with a recent hypothesis that in the presence of VEGF , angiopoietin-2 may collaborate at the front of invading vascular sprouts , serving as an initial angiogenic signal that accompanies tumor growth. (Am J Pathol 1999Pathol , 155:1967Pathol -1976
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