A Noninvasive Encapsulated Macrofollicular Variant of Papillary Thyroid Carcinoma Presenting with Gross Lymph Node Metastasis: A Case Report and Literature Review

Abstract

Dear Editor:The follicular variant of papillary thyroid carcinoma (FV-PTC) without vascular or capsular invasion is considered tohave virtually no metastatic potential or recurrence risk (1).The macrofollicular variant of papillary thyroid carcinoma(MFV-PTC) is a very rare variant of FV-PTC the behavior ofwhich appears to be similar to FV-PTC (2). However, morerecently, this phenomenon has been challenged by reports ofsystemic metastases and recurrent and fatal cases (3). We re-port a case of encapsulated noninvasive MFV-PTC that pre-sented with gross lymph node metastases, and briefly reviewthe literature. A right thyroid nodule was incidentally foundby a computed tomography scan in an 80-year-old male.Subsequently, a 3.7cm·3.6cm·3.3cm heterogeneous iso- tohyperechogenic thyroid nodule in the right lobe and a2.2cm·2cm·1.3cm right jugular lymph node, both withcalcifications, were detected by ultrasonography. Fine-needleaspiration biopsy of both lesions was performed under ultra-sonography guidance and showed malignant cells consistentwith PTC. The patient underwent a total thyroidectomy withcentral and right (levels 3–4) lymph node dissection. Thethyroidectomy specimen revealed a 3.7cm·3.2cm·2.9cmencapsulated white solid nodule in the right lobe (Fig. 1),which was entirely submitted for histological evaluation. Onhistology, the nodule was completely surrounded by a thickand focally calcified capsule, without evidence of vascular orcapsular invasion. The nodule was predominantly macro-follicular, with minor areas composed of smaller follicles. Thecells lining the macrofollicles were often attenuated withoutsignificant nuclear atypia (Fig. 1). In contrast, the cells liningthe smaller follicles were more cuboidal and had the typicalnuclear features of PTC (Fig. 1). Numerous intratumoral cal-cifications and psammoma bodies were observed (Fig. 1).Insular/solid growth, necrosis, or mitotic activity was notobserved. Two lymph node metastases were found. Thelargest one (2.4cm) was composed predominantly ofmacrofollicles, akin to the primary tumor (Fig. 1). Im-munohistochemistry was supportive of malignancy, withthe tumor cells being diffusely positive for galectin-3, andfocallypositiveforHBME-1(HectorBattiforamesothelin-1)inthe non-macrofollicular areas only. The proliferative index(Ki-67) in the primary tumor and in the larger metastasis wasvery low ( 50%) was composed ofmacrofollicles (>250lm), corresponding to the arbitrarydefinition of an MFV-PTC (2). Interestingly, that feature wasalso retained in the larger lymph node metastasis, but not inthe smaller one. In the literature, although several cases ofMFV-PTC have presented with lymph node metastasis, mostof these cases were either infiltrative and/or associated withvascular invasion (2). In the largest series of MFV-PTC of 29patients, 6 developed lymph node and 2 developed lungmetastasis (2). The metastases occurred in older patients whohad insular components, extrathyroidal extension, and vas-cular invasion. In our case, although the patient was elderly,no other risk factors were identified. To the best of ourknowledge, there are two other documented cases of encap-sulatedMFV-PTCwithoutcapsularorvascularinvasionwithlymph node and/or systemic metastasis (3). In comparison,we found no well-documented cases of conventional encap-sulated noninvasive FV-PTC with lymph node metastases. Inthe study by Liu et al. (1), the only encapsulated FV-PTC withlymph node metastasis had several foci of lymphovascularinvasion. Moreover, observing that most cases of FV-PTCwith metastatic disease had obvious invasion, Lloyd et al. (4)recommend caution in making a diagnosis of FV-PTC in theabsence of the major histopathologic features or obvious