Cytomorphological and clinical features of follicular variant papillary thyroid carcinoma (with focal insular pattern) metastasis to kidney

Abstract

Follicular variant of papillary thyroid carcinoma (FV-PTC) is the second most common subtype of PTC after the classic PTC. FV-PTC is characterized by nuclear features of classic PTC with a follicular architecture that lacks classic papillary morphology. Unlike follicular thyroid carcinoma (FTC), which is more often manifested by hematogenous metastases to lung and bone, PTC tends to metastasize to cervical lymph nodes. Distant metastases of PTC are very rare, whereas renal metastasis is extremely rare.[1] Renal fine-needle aspiration (FNA) is not commonly used due to concerns about safety and diagnostic accuracy. However, it can be used for diagnosis in poor surgical candidates or patients with unresectable tumors and for excluding metastasis, hematologic malignancy, and benign or reactive processes.[2] Here, we report the cytomorphological and clinical features of a 74-year-old female patient with renal mass diagnosed as FV-PTC metastasis with FNA. We report this case because of the rarity of renal metastasis of FV-PTC, which can be a diagnostic pitfall in the evaluation of renal FNA. A 74-year-old woman presented for evaluation of a right renal mass, and she did not have any urinary symptoms such as hematuria or pain. Computerized tomography (CT) of abdomen revealed a 29 × 28 mm homogeneous solid mass arising from the upper pole of the right kidney. The medical history of the patient indicated a total thyroidectomy performed at our hospital 7 years ago. The histologic type of tumor was identified as FV-PTC (with focal insular pattern and extrathyroidal extension). A recent fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan of the patient revealed multiple hypermetabolic pulmonary and bone metastasis as well as an additional new hypermetabolic lesion with an SUVmax value of 7.5 on right upper renal pole [Figure 1].Figure 1: FDG-PET/CT scan maximum intensity projection (MIP) image revealing intense FDG uptake on upper pole of right kidney, which was proven to be thyroid cancer metastasis on histopathology (black arrow). She also had multiple bone metastases and pulmonary metastases with increased FDG uptakeCT-guided FNA was performed on renal mass for diagnosis. Very few cells were found on slides by rapid on-site evaluation; however, a second FNA could not be performed because the patient was unable to tolerate the procedure. In cytological evaluation, the slides were hypocellular, but the hematoxylin and eosin slides of cell block were rich in tumoral cells. The small- to medium-sized tumor cells with a follicular architecture with slightly monomorphic atypia were seen [Figure 2]. An immunohistochemical study was carried out in cell block to support the diagnosis. Tumor cells were positive for CK7, thyroid transcription factor-1 (TTF-1), thyroglobulin, and focal positive for CD56. No staining was observed with PAX2 [Figure 3]. The case was assessed with previous slides of thyroid resection. The same histological features were seen. With these findings, the case was reported as renal metastasis of FV-PTC.Figure 2: Conventional slides were very hypocellular, and there were only a few tumor cells in the follicular pattern (a, May-Grünwald-Giemsa (MGG), x200; b, MGG, x400). In cell block sections, small- to medium-sized tumor cells with a follicular architecture that had slightly monomorphic atypia were seen (c, hematoxylin and eosin (H and E), x200; d, H and E × 400)Figure 3: The immunohistochemical stains (a, TTF-1, x200; b, CK7, x200; c, thyroglobulin, x200; d, CD56, x200; e, PAX2 × 200)Renal metastasis is very uncommon in cases of well-differentiated thyroid carcinomas.[1] Diagnosis of FV-PTC by FNA aspiration cytology is difficult because they do not have all cytologic features of classical PTC, such as papillary structures consisting of fibrovascular cores, or the nuclear features like nuclear enlargement and overlap, chromatin clearing, grooves, and intranuclear pseudo inclusions. FV-PTCs often show microfollicular patterns in cytologic specimens and are frequently classified under the “follicular neoplasm/suspicious for a follicular neoplasm” or “suspicious for PTC” category within the Bethesda System, according to the severity of atypia.[3] A diagnostically challenging lesion in the differential diagnosis of metastatic FV-PTC is FTC, showing a microfollicular pattern or a further cytologic feature such as a solid trabecular or cribriform pattern. Furthermore, both lesions have identical propensity to metastasize to lung and bone by hematogenous instead of lymphatic route as in conventional PTC.[3] In addition, FV-PTC also represents various genetic abnormalities with FTC, including RAS mutations and PAX8/PPARg rearrangements.[4] In differential diagnosis, thyroid-like follicular carcinoma (TLFC) of the kidney, which is an extremely rare type of renal tumor, was considered. Histologically, TLFC consists of follicles of various sizes filled with colloid-like material. These tumors are immunoreactive for PAX2, PAX8, and CK7 but lack reactivity for thyroglobulin and TTF-1.[5] In the present case, immunohistochemical analysis was performed for differential diagnosis. The tumor cells were immunoreactive for CK7, TTF-1, thyroglobulin, and focal positive for CD56 but PAX2-negative. These immunohistochemical results supported our diagnosis of renal metastasis of FV-PTC. In our case, there was a focal insular pattern with FV-PTC and extrathyroidal extension. It is known that insular thyroid carcinomas have a high incidence of metastasis, recurrence, mortality, and poor prognosis.[6] Focal insular pattern may explain the aggressive behavior and the large number of distant metastases of the initial carcinoma. In conclusion, metastatic tumors in the kidney can be difficult to diagnose on cytologic specimens. In our case, the patient’s clinical history of FV-PTC and immunohistochemical studies were helpful in distinguishing other tumors and supported the diagnosis. In differential diagnosis of renal masses, metastases of thyroid-origin carcinomas should be kept in mind. Future reports of similar cases may improve the awareness of this pathology and enrich the literature. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.