Histopathologic characterization of radioactive iodine‐refractory fluorodeoxyglucose‐positron emission tomography‐positive thyroid carcinoma

Abstract

BACKGROUND.Radioactive iodine‐refractory (RAIR) 18F‐fluorodeoxyglucose (FDG)‐positron emission tomography (PET) positive thyroid carcinomas represent the major cause of deaths from thyroid carcinomas (TC) and are therefore the main focus of novel target therapies. However, to the authors' knowledge, the histology of FDG‐PET‐positive RAIR metastatic thyroid carcinoma has not been described to date.METHODS.Metastatic tissue from RAIR PET‐positive patients identified between 1996 and 2003 at the study institution were selected for histologic examination. The biopsied metastatic site corresponded to a FDG‐PET positive lesion sampled within 2 years (87% of which were sampled within 1 year) of the PET scan. Detailed microscopic examination was performed on the metastatic deposit and the available primary tumors. Poorly differentiated thyroid carcinomas (PDTC) were defined on the basis of high mitotic activity (≥5 mitoses/10 high‐power fields) and/or tumor necrosis. Other types of carcinomas were defined by conventional criteria. The histology of the metastases and primary were analyzed, with disease‐specific survival (DSS) as the endpoint.RESULTS.A total of 70 patients satisfied the selection criteria, 43 of whom had primary tumors available for review. Histologic characterization of the metastasis/recurrence in 70 patients revealed that 47.1% (n = 33 patients) had PDTC, 20% (n = 14 patients) had the tall cell variant (TCV) of papillary thyroid carcinoma, 22.9% (n = 16 patients) had well‐differentiated papillary thyroid carcinoma (WDPTC), 8.6% (n = 6 patients) had Hurthle cell carcinoma (HCC), and 1.4% (n = 1 patient) had anaplastic carcinomas. The histopathologic distribution of the tumor in the primaries was: PDTC, 51%; TCV, 19%; WDPTC, 23%; and widely invasive HCC, 7%. A differing histology between the primary tumor and metastasis was observed in 37% of cases (n = 16 patients). In the majority of instances (63%; 10 of 16 patients) this was noted as transformation to a higher grade. Of the primary tumors classified as PTC, 70% progressed to more aggressive histotypes in the metastasis. Tumor necrosis and extensive extrathyroid extension in the primary tumor were found to be independent predictors of poorer DSS in this group of patients (P = .015). Approximately 68% of the PDTC primary tumors were initially classified by the primary pathologist as better‐differentiated tumors on the basis of the presence of papillary and/or follicular architecture or the presence of typical PTC nuclear features.CONCLUSIONS.Several observations can be made based on the results of the current study. The majority of metastases in patients with RAIR PET‐positive metastases are of a histologically aggressive subtype. However, well‒differentiated RAIR metastatic disease is observable. Poorly differentiated disease is underrecognized in many cases if defined by architectural and nuclear features alone. The presence of tumor necrosis was found to be a strong predictor of aggressive behavior, even within this group of clinically aggressive tumors. Finally, there is a significant amount of histologic plasticity between primary tumors and metastases that may reflect the genetic instability of these tumors. Cancer 2008. © 2008 American Cancer Society.

Do histological, immunohistochemical, and metabolic (radioiodine and fluorodeoxyglucose uptakes) patterns of metastatic thyroid cancer correlate with patient outcome?

“…FDG uptake is correlated with clinical factors predicting a poor survival and the absence of response to 131 I treatment, such as age over 45 years and the presence of necrosis (LiVolsi & Baloch 2002, Durante et al 2006, Rivera et al 2008). Necrosis and mitosis that are interrelated have already been shown to be highly prognostic in other endocrine cancers (La Rosa et al 2009, Lau & Weiss 2009, and in recent studies, they were considered essential for the diagnosis of poorly differentiated thyroid carcinoma (Volante et al 2004a(Volante et al ,b, 2007.…”

Histologic coagulative tumour necrosis as a prognostic indicator of aggressiveness in renal, lung, thyroid and colorectal carcinomas: A brief review

“…Within this group of patients, microstaging (tumour size, the extent of capsular invasion, and extrathyroid extension), rather than growth pattern or cell type, is capable of stratifying patients into various prognostic categories (6). These findings indicate that grading of thyroid carcinoma based on increased mitotic activity, necrosis, nuclear pleomorphism and invasiveness is of high clinical and prognostic significance, whereas architectural grading has not yet been clearly proven to have any prognostic value (6)(7)(8)(9)11,18,19).…”

Poorly Differentiated Thyroid Carcinoma: 5 Years after the 2004 WHO Classification of Endocrine Tumours

“…However, standard postoperative dosages of 131 I do not differ from those of well 8 differentiated thyroid cancer [17,23]. It is worth noticing that recently a high prevalence of PDTC histotype was found in a series of radioiodine refractory metastatic thyroid cancers, and that, in this specific subgroup of patients, the presence of necrosis and extrathyroidal extension were associated to shorter disease-specific survival [27].…”