Observer Variation in the Diagnosis of Follicular Variant of Papillary Thyroid Carcinoma

Abstract

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Papillary carcinoma of the breast lacks evidence of RET rearrangements despite morphological similarities to papillary thyroid carcinoma

“…Such differences between these two forms of papillary carcinoma of the breast are not surprising given the unique nature of solid papillary carcinoma. 20,21 It is also interesting that our frequencies of nuclear clearing (27%) and nuclear inclusions (3%) in papillary carcinoma of the breast, both cytological features that some consider more specific for papillary thyroid carcinoma, 7,22,23 were considerably less common than nuclear overlap (73%) and nuclear grooves (42%). This suggests that these latter two features alone are probably not very useful for the diagnosis of papillary thyroid carcinoma outside the confines of the thyroid gland, where one may encounter a large variety of cell types harboring nuclear grooves.…”

The Impact of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma on Rates of Malignancy for Fine-Needle Aspiration Diagnostic Categories

“…In the past decade it has become clear that not all FVPTCs are biologically alike. FVPTCs with an infiltrative growth pattern, which account for roughly 20% of FVPTCs, are associated with frequent lymph node metastases and a risk of recurrence (2,3,23). Additionally, about a quarter of infiltrative FVPTCs harbor the BRAF V600E mutation and a small percentage have a RET/ PTC rearrangement (6).…”

“…Although this finding has significant implications, it must be noted that these findings are specific for our institution. Because the decrease in the risk of malignancy depends on the prevalence of the diagnosis of FVPTC, and FVPTC is known to be a diagnosis with low interobserver reproducibility (23,30), it is essential that additional studies are performed at other institutions. The magnitude of the impact will vary, and the biggest impact will be seen at institutions where the rate of diagnosis of FVPTC is the highest.…”

Microarray analysis refines classification of non-medullary thyroid tumours of uncertain malignancy

“…However, for decades, conventional histology failed to classify some encapsulated follicular thyroid tumours as benign or malignant because these lesions share overlapping histological features. This already known difficulty is underscored by recent substantial interobserver variability (Hirokawa et al, 2002;Franc et al, 2003;Lloyd et al, 2004), either in the pathological assessment of thyroid nodules or in the identification of underlying diagnosis criteria, such as papillary nuclear features, vascular and/or capsular invasion. These difficulties are especially relevant in encapsulated differentiated thyroid carcinomas for their belonging to the encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) or the minimally invasive FTC group, and for their ability to harbour predominant oncocytic features.…”