<p>Medullary Thyroid Carcinoma in a Patient with MEN 1 Syndrome. Case Report and Literature Review</p>

Abstract

Medullary thyroid cancer (MTC) is typically associated with multiple endocrine neoplasia type 2 syndrome (MEN 2), but not with multiple endocrine neoplasia type 1 (MEN 1). We report a very rare case of MTC in a patient with MEN 1 syndrome. A 60-year-old Caucasian woman with sporadic MEN 1 syndrome was admitted in October 2018 for recurrent hyperparathyroidism unresponsive to medical therapy. Her medical history included the diagnosis of a non-functioning pancreatic neuroendocrine tumor (NF-pNET) of the head of the pancreas 1.5 cm in size in 2001, and subtotal parathyroidectomy for uncontrolled hyperparathyroidism due to bilateral parathyroid hyperplasia in the same year. This history prompted genetic studies, and MEN 1 syndrome was confirmed. Family screening was performed in first-degree relatives, with negative results. Other typical clinical manifestations of MEN 1 syndrome were ruled out. In November 2018, the patient underwent excision of the residual left inferior parathyroid, extended to include the left thyroid lobe, for recurrent uncontrolled hyperparathyroidism. The pathologist identified MTC and adenoma of the parathyroid gland. Genetic tests were performed to identify any RET mutation, with negative results. The patient underwent total thyroidectomy about 6 months later, and the subsequent histological report showed only focal reactive C-cell hyperplasia of the thyroid. A literature review identified only three previously published cases of MTC coexisting with MEN 1 syndrome. This association may have two etiological hypotheses: either a sporadic MTC arising in a patient with MEN 1 syndrome, or a rare case of medullary cancer linked to a MEN 1 gene mutation.

Evaluation of multinodular goiter and primary hyperparathyroidism leads to a diagnosis of AL amyloidosis

“…It is crucial to rule out medullary thyroid carcinoma as the etiology especially in this patient given there is concern for MEN. Medullary thyroid carcinoma is a common manifestation associated with MEN2, a more likely possibility in this patient but there are a few rare case reports of MTC occurring in MEN1 [ 11 ]. Amyloid deposit in the parathyroid glands is also clinically rare and can go easily undetected in patients with systemic amyloidosis [ 12 ].…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…At a lower level of statistical evidence, we mention the sample-focused analysis of case reports with regard to the parathyroid and pancreatic MEN1-NETs having a specified genetic confirmation of the MEN1 pathogenic variant (regardless of if the type was detailed by the original authors) [ 68 , 73 , 75 , 77 , 81 , 97 , 100 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ] ( Table 6 ).…”

“…There were 24 MEN1 subjects (including index cases with genetic analysis for their relatives) within 24 papers; they were aged between 17 years (only two pediatric cases were found) and 74 years; the female-to-male ratio was 0.84. The female population (N = 11) had an average age of 43.63 years (ranges between 28 and 60); males (N = 13) had a mean age of 40.07 years (ranges between 17 and 74) [ 68 , 73 , 75 , 77 , 81 , 97 , 100 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ].…”

“…Notably, with respect to the overall MEN1 presentation, we mention adults with two lipomas [ 77 ] or a single giant cervical lipoma [ 125 ]; for the synchronous thyroid malignancy of papillary [ 81 ] and medullary type in a RET -negative patient [ 128 ], two MEN1 subjects displayed a thymus carcinoid as the first MEN1 manifestation [ 129 , 132 ].…”

“…Notably, in the study conducted by Shyamasunder et al [ 114 ], seven out of the ten individuals who, despite being suspected with MEN1, were found MEN1 -negative carried a p.V109G polymorphism in the CDKN1B gene, which required additional testing to be highlighted as pathogenic variant [ 114 ]. As prior specified, the fourth ever case of RET -negative medullary thyroid carcinoma in a MEN1-positive patient was reported in 2020, suggesting than a larger dichotomy in understanding this field should be kept in mind [ 128 ]. An additional case was reported in 2022 [ 142 ].…”