Case presentation
A 63-year-old woman presented in 2022 due to an enlarged mediastinum measuring 4.2×2.4 cm incidentally observed on a chest computed tomography (CT) scan during a routine health check-up (see timeline in Fig. 1A, enhanced CT in Fig.1B). Her prior medical history was remarkable for resection of nonfunctional pituitary macroadenoma in 2007 and 2008 successively complaining visual field defects. In 2010 at the age of 51 years, she presented to the clinic with recurrent reduced consciousness and hypoglycemia of 1.7mmol/L. Symptoms resolved in 5-10 minutes with intravenous dextrose. Plasma insulin (47.6uIU/mL) and C-peptide (4.7ng/ml) were high. Subsequent imaging identified multifocal lesions in the head and neck of the pancreas. Tumor enucleation was performed in November 2010—pathology documented an islet cell tumor. In addition to insulinoma, laboratory testing revealed an inappropriately normal intact parathyroid hormone (iPTH) level of 596ng/L (normal range 12-68), corrected calcium values of 2.99mmol/l(normal range 2.13-2.70), associated with low phosphorus levels (0.68mmol/l, normal range 0.81-1.45). The neck ultrasound showed a 10 mm round hypoechoic nodule posterior to the right inferior thyroid lobe with undefined margins. The same lesion was detected by Technetium-99m MIBI scan, documenting a persistent uptake. The pathology from a right-sided parathyroidectomy was consistent with parathyroid hyperplasia. She reported a family history of insulinoma in her elder sister.
On admission, swelling of the face, neck, or upper body and dyspnea or distended neck veins were not observed. Furthermore, 18-FDG PET/CT showed intense glucose uptake from a 4.5cm mediastinal mass, suspicious of malignant thymic lesions with a SUVmax value of 11.9. (Fig. 1C).
Concurrent with the mediastinal mass, primary hyperparathyroidism was observed following normal-high free cytoplasmic calcium (1.26mmol/L) and 24-hour urinary calcium of level 7.42mmol/L in the setting of elevated parathyroid hormone levels (88ng/L). The neck ultrasound and parathyroid MIBI scan showed uptake consistent with a 10 mm left inferior parathyroid adenoma. There was no evidence of renal dysfunction, urolithiasis, or loss of bone mass. Repeat MRI identified a possible 2.3cm pituitary macroadenoma (Fig. 1D-E) that has remained stable. Pituitary hormone levels have always been normal. Pancreatic perfusion CT showed multiple calcification foci and a small nodular shadow in the pancreatic body and tail. She underwent whole gene sequencing that found a heterozygous, pathogenic splice donor variant in the MEN1 gene(c.783+1G>A), confirming a diagnosis of MEN1.To rule out other endocrinopathies, serum gastrin, calcitonin, glucagon levels, C-peptide, fasting blood glucose, and urinary catecholamine test was performed and resulted in range.
Thoracoscope surgery was performed in August 2022 after a multidisciplinary board composed of endocrinologists, pancreatic surgeons, thoracic surgeons, anesthesiologists, neurosurgeons, and an intensive care unit. No tumor invasion to the pericardium and lung was observed, and the tumor was removed entirely. Pathologists diagnosed thymoma (WHO type B3, Fig.1F-I). The tumor had a Ki67 proliferation index of 20%. Immunolabelling with CK19 was positive and Syn was negative. Postoperatively, she was referred for consideration for external beam radiation therapy and will continue to undergo routine surveillance for all aspects of MEN 1 disease. Genetic testing for her daughter is being considered. At six months from surgery, the patient is in good condition and disease-free, as demonstrated by the physical examinations and tests to which he is regularly submitted.
Electronic literature search
We searched PubMed and EMBASE (1974 to 6 Feb 2023). Mesh terms and free-text words were matched and used together for database searches using combinations of keywords: multiple endocrine neoplasia type 1; MEN1; thymoma; mediastinum; mediastinal; thymic; thymus; thoracic. The reference lists of all relevant articles were also searched to identify additional potentially relevant studies. The selection process is documented in a detailed flowchart (Fig. 2). Eligible studies included those reporting the outcomes of patients with thymoma associated with MEN1 and met the following inclusion criteria: (i) patients fulfilled the clinical, genetic, and/or familial criteria for MEN1 based upon the clinical practice guidelines [1]; (ii) the diagnosis of thymoma was based on histopathological results either from surgery or core needle biopsy; and (iii) the study was written in English. We excluded studies from this review if they were the following: (i) review articles, case reports, family studies, conference abstracts, and letters; (ii) studies without clinical data. Among the final cases, clinical characteristics, including sex, age, ethnicity, symptoms, family history, pathological classification and size of the tumor, components of MEN1, and treatment, were summarized.