Medullary Thyroid Cancer with Paraganglioma-Like Pattern Diagnosed During Pregnancy: A Case Report and Literature Revision

Abstract

Introduction: Medullary thyroid carcinoma (MTC) is an infrequent thyroid malignancy rarely observed and managed during pregnancy. An accurate diagnostic workup is extremely important in this clinical setting to correctly diagnose and treat the disease, avoiding both maternal and fetal complications. Objective: We report our experience in managing an MTC incidentally diagnosed during pregnancy in a 28-year female, highlighting critical aspects through the diagnostic workup. Additionally, we provide a literature revision searching on PubMed terms related to “medullary thyroid carcinoma”, “primary thyroid paraganglioma”, “paraganglioma-like medullary thyroid cancer” in relationship with a nodular appearance at neck US, serum CT measurement, cytological and histological findings. Methods: Specimens for cytological evaluation were stained with the Papanicolaou method while tissue sections were stained with hematoxylin and eosin and Congo red stain. Immunohistochemical evaluation was also performed for thyroid transcription factor-1, enolase, thyroglobulin, cytokeratin, chromogranin A, S-100 protein, glial fibrillary acidic protein, calcitonin and Ki-67. Results: Serum CT was incidentally found to be elevated in two consecutive venous samples. However, the cytological assessment of the fine needle aspiration (FNAc) showed “cells with round-shaped nuclei and granular chromatin, organized to form nests or syncytial flaps, scattered among histocytes, and immunocytochemical positivity for CT, thyroid transcriptional factor-1, cytokeratin, S-100 protein”, highlighting a suspicion of both MTC and intrathyroidal paraganglioma. MTC was finally supposed after the evidence of a really elevated CT (3,726 pg/ml) measurement in the FNA washout fluid. After a careful discussion about both risks and benefits, the patient decided to postpone the surgery after the delivery. Conclusion: The histological diagnosis finally confirmed a rare case of paraganglioma-like MTC (T1 N0 Mx), emphasizing the complexity of our differential diagnosis, between an MTC and a thyroidal paraganglioma. In similar cases, due to a relevant impact on surgical timing, patients should be adequately informed about both risk and benefits of the surgery during pregnancy, and a careful management of the disease is required until and after surgery.

Cytologic and histological features of rare nonepithelial and nonlymphoid tumors of the thyroid

“…The cytological diagnosis of paraganglioma is challenging and, not surprisingly, might lead to misdiagnoses. FNA smears are cellular and contain single cells or loose clusters of medium to large cells 37,41‐43 . The neoplastic cells have epithelioid, plasmacytoid, and spindle features.…”

“…The smears are characterized by a bloody background and lack colloid or an amyloid component. Malignancy in paraganglioma cannot be reliably diagnosed on cytological smears (or histology) 41‐43 …”

“…Multifocal tumors may be seen in patients with familial paraganglioma-pheochromocytoma syndrome, defined by a mutation in the succinate dehydrogenase subunit genes SDHD, SDHC, or SDHB. 1,2,[37][38][39][40][41][42][43][44][45]…”

“…FNA smears are cellular and contain single cells or loose clusters of medium to large cells. 37,[41][42][43] The neoplastic cells have epithelioid, plasmacytoid, and spindle features. They have scant to moderate basophilic cytoplasm, round to oval nuclei, open chromatin, and inconspicuous nucleoli (Fig.…”

“…Malignancy in paraganglioma cannot be reliably diagnosed on cytological smears (or histology). [41][42][43]…”