Abstract
Introduction: Medullary thyroid cancer (MTC) is a rare tumor of neuroendocrine origin that co-secretes various peptides leading to diarrhea and vasodilation. Ectopic Cushing syndrome due to production of adrenocorticotropic or corticotrophin-releasing hormone is a well-recognized but uncommon paraneoplastic manifestation of advanced MTC. We report an extremely rare presentation of eosinophilia in a patient with MTC that correlated with disease progression. Case:
A 58-year-old woman with sporadic metastatic MTC harboring somatic RET M918T mutation developed metastatic disease to the liver, lung and bones 2 years after surgery for locally advanced disease. Calcitonin (Ctn) was 123 pg/ml and CEA was 2575 ng/ml. At that time, leukocytosis [WBC 30.8 K/ul (4-11k/ul)] and eosinophilia [eosinophil count 16.01 k/ul (0.04-0.40 k/ul)] were noted. She was asymptomatic. Extensive evaluation of hypereosinophilia ruled out hematological or infectious causes. The patient initiated vandetanib with a partial response (PR) with decrease in lung and liver metastases and a significant improvement of the paraneoplastic eosinophilia [eosinophil count 2.39 k/ul] after 10 weeks of treatment. After a year on treatment, there was progressive disease (PD) with increasing hilar and abdominal lymphadenopathy associated with increased eosinophilia of 4.34 K/ul. Vandetanib was discontinued. She was enrolled on a clinical trial with a highly potent and selective RET inhibitor. The patient achieved PR to study drug by the 2nd month on treatment and durable response for 30 months. The eosinophil count normalized [0.32 k/ul] 4 weeks after starting the new treatment. She developed PD in liver metastases associated with recurrent leukocytosis (WBC 58.6 K/ul) and eosinophilia of 28.13 K/ul. Ctn was 1646 pg/ml. CEA was 8722 ng/ml. Her bone marrow biopsy showed marked eosinophilia, focal MTC metastatic infiltrate, no increased blasts, and was negative for the BCR-ABL1 translocation and the FIP1L1-PDGFRA fusion. She was switched to a different RET Inhibitor but passed away 1 month after starting the new protocol. Discussion: Paraneoplastic eosinophilia should be considered after excluding other causes (e.g. infections, allergy, collagen, vascular or malignant hematopoietic diseases). Thyroid tumors producing colony-stimulating factors, associated with neutrophilia and/or eosinophilia have been described almost exclusively in patients with anaplastic thyroid cancer. This patient had a poorly differentiated MTC as evidenced by the disproportionally high CEA relative to Ctn. The course of the eosinophilia paralleled the clinical behavior of her disease. To our knowledge, this is only the 2nd report of eosinophil trends corresponding with MTC disease course, consistent with a paraneoplastic process. Conclusion: PNE is very rare in MTC and its presence suggests a poor prognosis.
Oncocytic adrenal tumour presenting as Cushing syndrome: rare presentation of a rare tumour
