Why There Is the Tendency to “Overdiagnose” the Follicular Variant of Papillary Thyroid Carcinoma (2002)

A story is told by Juan Rosai about an atypical melanocytic lesion sent to him in consultation from a pathologist friend in private practice. After a long study, Dr Rosai decided it was benign. His friend thanked him for his opinion, but told him that he was still going to diagnose it as malignant melanoma. He said that if he called it melanoma and it never came back, everyone would be happy that the patient was cured. If he called it benign and it came back, then he would end up in court. This is the dilemma that faces the practicing pathologist every day. The tendency to “overdiagnose” seems to be inevitable as long as there is a surfeit of aggressive, unforgiving malpractice attorneys as well as pathology experts and a limited risk to the “overdiagnosis.” This tendency to overdiagnose clearly is accentuated in private practice. Fueled by the perception that private practitioners are not as good as their academic counterparts, cases in growing numbers are being referred to the university setting for a second opinion, sometimes years after the case originally was signed out. If the diagnosis from this second opinion on a thyroid nodule is malignant when the original diagnosis was benign, the ramifications can be quite devastating. While there certainly are benefits to second opinions,1 and we are in no way arguing against them, the unintended result of this practice is to render the private pathologist more vulnerable, more prone to litigation, and more likely to overdiagnose. Defensive pathology is now so ingrained in the psyche of most private pathologists that it has become second nature. The purely follicular variant of papillary thyroid carcinoma (PTC) described by Lindsay in 19602 and later popularized by Chen and Rosai3 and Rosai et al4 is now well accepted. The nuclear features have become tantamount to papillary structures in the diagnosis of PTC. The nuclear features include the following: (1) overlapping ground-glass, optically clear, or “Orphan Annie” nuclei and (2) nuclear pseudoinclusions and grooves, which represent cytoplasmic invaginations into the nucleus. Despite the universal recognition of this variant, it is not well characterized. The conventional PTC is classically an invasive tumor even when the majority of it is composed of follicles. The purely follicular variant of PTC on the other hand is often well circumscribed and encapsulated.4 What clearly is lacking is a minimal histologic definition of the follicular variant of PTC. Is an occasional grooved nucleus with pale chromatin in a follicular neoplasm enough to warrant a diagnosis of malignancy? Should the nuclear changes be uniformly present throughout the nodule? Are the nuclear changes that we are seeing significant or are they the “pseudoclear nuclei” described by Hapke and Dehner in the 1970s?5 At present, there are only a few long-term follow-up studies (totaling only 107 patients, as nicely summarized by Chan6) of the encapsulated follicular variant of PTC. While it is true that only 1 of these 107 patients died of disease,7 more than 25% of these patients had regional lymph node metastases. In addition, a recent study by Baloch and LiVolsi8 described 5 cases in which the encapsulated follicular variant of PTC manifested as an occult primary with metastatic disease, or in which bone metastases appeared many years after resection, and invasion in the primary lesion was subtle enough to be overlooked. Another study documented rare clinical progression (lymph node metastases) in the macrofollicular variant of PTC despite the fact that the dominant cytology and architecture of the primary tumor very closely resembled goiter.9 In summary, although the follicular variant of PTC usually behaves in a very indolent fashion, it rarely can cause distal metastasis. Furthermore, the follicular variant