Parathyroid carcinoma in multiple endocrine neoplasia type 1 (MEN1) syndrome: Two case reports of an unrecognised entity
ABSTRACT Primary hyperparathyroidism occurs in almost all patients with the syndrome of multiple endocrine neoplasia type 1 (MEN1), but the association of MEN1 with parathyroid carcinoma has only been described previously in a single patient. In this report, we describe two further cases of parathyroid carcinoma presenting in MEN1 syndrome.
The first patient was a 69-yr-old woman, who presented with severe primary hyperparathyroidism and tracheal compression by a large mediastinal mass, which was shown histologically to be a parathyroid carcinoma with a second similar lesion in the neck. She was treated with total parathyroidectomy followed by resection of the mediastinal mass with resolution of the hypercalemia. Remarkably, she also reported primary amenorrhea and was found to have an invasive pituitary lactotroph adenoma, which was treated with cabergoline and external beam radiotherapy. Magnetic resonance imaging (MRI) of the pancreas revealed a small lesion characteristic of an islet-cell tumor, which was clinically and biochemically non-functioning. The second patient was a 32-yr-old man who presented with symptomatic hypercalemia and markedly raised serum PTH concentration. Neck exploration revealed two parathyroid glands only. One of the parathyroid glands contained a tumor with fibrous banding, atypical mitoses, extra-capsular extension and moderate Ki 67 staining; features which are highly suggestive of carcinoma. He also had intractable dyspepsia associated with raised serum gastrin concentration. A lesion was localized to the neck of the pancreas by endocopic ultrasound, and a selective arterial calcium stimulation catheter suggested the presence of both a gastrinoma and an insulinoma, although he had no hypoglycemic symptoms. Pituitary MRI was normal. The patient's mother had primary hyperparathyroidism.
This case report describes two further patients in whom parathyroid carcinomas occurred in the context of MEN1, which gives a new insight to the possible presenting phenotype of this condition. Both patients had negative genetic screening for classic MEN1 gene mutation, which may suggest that one or more novel occult mutations may be responsible for this aggressive phenotype.
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ABSTRACT: A 53-year-old man with no past medical history was admitted with complaints of hematuria, flank and abdominal pain of one week duration. He also complained of an enlarging new neck mass one month before presentation. The laboratory assessment showed a calcium level of 17.3 mg/dL (normal 8.5-10.5 mg/dL), serum albumin 2.9 g/dL (normal 3.0-5.0 g/dL), serum creatinine 3.4 mg/dL (normal 0.5-1.2 mg/dL). A neck ultrasound showed a complicated left neck mass. He was hydrated for one week with improvement in his labs, showing a decrease in serum calcium to 9.3 mg/dL and a serum creatinine of1.8 mg/dL. He underwent a total thyroidectomy and parathyroidectomy. The pathology showed multiglandular parathyroid carcinoma. It is important for the physician and surgeon dealing with primary hyperparathyroidism to look for parathyroid carcinoma. A better knowledge and understanding of this condition would aid in early diagnosis and possibly increase the survival rate.Southern Medical Journal 09/2007; 100(8):841-4. DOI:10.1097/SMJ.0b013e318073ca37 · 1.12 Impact Factor
Article: Parathyroid Carcinoma[Show abstract] [Hide abstract]
ABSTRACT: The best opportunity to cure parathyroid carcinoma is to diagnose it before or at the time of parathyroid surgery and for the tumor to be completely removed at the time of the initial operation. Because the diagnosis is often not clear at the time of presentation, recent attempts to distinguish between benign and malignant disease both by genetic and immunohistological analyses are promising. The disease is indolent but progressive. Attempts to remove local recurrences and distant metastases can provide short- and long-term control. Other therapeutic approaches with chemotherapy and radiotherapy are not helpful. Available medical therapy targets the consequence of the disease (hypercalcemia) rather than the disease itself.Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2009; 23(12):1869-80. DOI:10.1359/jbmr.081018 · 6.59 Impact Factor
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ABSTRACT: MEN 1 is a rare hereditary cancer syndrome which manifests a variety of endocrine and non-endocrine neoplasms and lesions. Growing knowledge of this condition in both its molecular genetic underpinnings and its clinical implications have affected the entire spectrum of the clinical management of MEN patients. The MEN1 gene is a tumor suppressor gene, and mutations in it account for the development of the MEN1 clinical syndrome through impairment of several cell functions, such as cell proliferations, cell growth control, apoptosis, DNA replication and repair, gene expression, transcriptional machinery control, and hormone secretion. Currently, DNA testing makes possible the early identification of germline mutations in asymptomatic mutation carriers. The ever increrasing combination of genetic and clinical tools will allow early detection of MEN1-associated neoplasms, potentially improving clinical outcomes and quality of life for both affected patients and their relatives.Genetics in medicine: official journal of the American College of Medical Genetics 11/2009; 11(12):825-35. DOI:10.1097/GIM.0b013e3181be5c97 · 6.44 Impact Factor