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: The concept of precursor lesions of endocrine neoplasms is a new and interesting topic in endocrine pathology. A variety of clinicopathological conditions are associated with a sequence of cellular changes from hyperplasia to neoplasia; dysplasia is, in contrast, quite rare. The majority of precursor lesions is associated with familial genetic syndromes. These include C-cell hyperplasia in thyroid that is associated with familial medullary thyroid carcinoma, adrenal medullary hyperplasia as a precursor of phaeochromocytomas in MEN2 syndrome, rare pituitary adenohypophyseal cell hyperplasia in familial syndromes associated with pituitary adenomas, MEN1-related precursor gastric enterochromaffin-like cell (ECL) hyperplasia, and duodenal gastrin producing (G) and/or somatostatin producing (D) cell hyperplasia that give rise to type II gastric neuroendocrine tumours (NETs) and duodenal NETs, respectively, and MEN1- or VHL-related islet hyperplasia, islet dysplasia and ductulo-insular complexes that are associated with pancreatic NETs. Other hyperplasias are not thought to be associated with genetic predisposition. Some are attributed to inflammation; autoimmune chronic atrophic gastritis-related ECL hyperplasia can progress to type I gastric NETs, and EC (enterochromaffin) cell or L cell hyperplasia associated with inflammatory bowel diseases can progress to colorectal NETs. In the lung, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia can give rise to peripherally-located low grade pulmonary NETs and tumourlets (neuroendocrine microtumours <5 mm). Rarely, secondary hyperplasias develop into autonomous neoplasms, as in tertiary hyperparathyroidism or pituitary thyrotroph adenomas in primary hypothyroidism. While some precursor lesions, such as thyroid C cell hyperplasia, represent frankly premalignant conditions, others may represent a sequence of proliferative changes from hyperplasia to benign neoplasia that may also progress to malignancy.Pathology 03/2013; DOI:10.1097/PAT.0b013e32835f45c5 · 2.62 Impact Factor
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ABSTRACT: Parathyroid carcinoma is a malignant neoplasm affecting 0.5% to 5.0% of all patients with primary hyperparathyroidism. Since it was first described by De Quervain in 1904 to this day, it continues to defy diagnosis and treatment because of its rarity, overlapping features with benign parathyroid disease, and lack of distinct characteristics. En bloc surgical extirpation of the tumor with clear margins remains the best curative treatment. Although prolonged survival is possible with recurrent or metastatic disease, cure is rarely achievable. Efficacy of adjuvant therapies, such as radiotherapy and chemotherapy, in management of persistent, recurrent, or metastatic disease has been disappointing.Hematology/oncology clinics of North America 12/2012; 26(6):1221-38. DOI:10.1016/j.hoc.2012.08.009 · 2.05 Impact Factor
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ABSTRACT: Introduction: Parathyroid carcinoma (PC) is a rare endocrine malignancy that still suffers from a problem of delayed clinical diagnosis. Consequently, it usually is not recognized preoperatively and often is not conclusively identified during the operation either. Areas covered: The role played by parafibromin in the development of PC, representing an important advance in understanding the pathogenesis of this malignancy, is discussed. Through a careful search of the international literature, using "parathyroid carcinoma", "molecular genetics of parathyroid carcinoma" and "parathyroid tumorigenesis" as key words, other less mentioned molecular mechanisms are reappraised as potential molecular markers of PC; we also discuss their potential role in 20 parathyroid outgrowths. Finally, both the major efforts and the limitations of reported molecular diagnostic techniques and diagnostic markers are considered. Expert opinion: Currently, several critical issues still need to be addressed, such as the lack of: i) common criteria for the histopathological diagnosis of parathyroid malignancy and ii) timely appropriated preoperative diagnosis of PC. The latter issue would be of fundamental importance to assist the surgeon in performing a complete resection of all carcinomatous tissue at the time of the initial surgery, allowing for the greatest likelihood of a cure.Expert Opinion on Medical Diagnostics 01/2012; 6(1):27-37. DOI:10.1517/17530059.2012.634796