title: Parathyroid carcinoma and atypical parathyroid neoplasms in MEN1 patients; A clinico-pathologic challenge. The MD Anderson case series and review of the literature.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 1 (MEN1) is a genetic disorder characterized by usually benign tumors of the parathyroid glands, pancreatic islet cells, and anterior pituitary. Hyperparathyroidism (HPT) occurs in 90% of MEN1 patients. In rare cases, it is associated with parathyroid carcinoma (PC) or atypical parathyroid neoplasm (APN). We present a cohort of 3 such patients.
  
  
  METHODS
  We performed a retrospective review of our institution's MEN1 database to identify patients who underwent operations for HPT and had a histopathologic diagnosis of PC or APN. Clinical features, genetics, and outcomes were summarized.
  
  
  RESULTS
  Of 291 MEN1 patients, 242 had HPT (83.2%). Two of the 242 patients (0.8%) had a histopathologic diagnosis of PC, and 1 (0.4%) had a diagnosis of APN. The patients with PC were male, ages 62 and 56 years at the time of surgery; the patient with APN was female, age 32 years. All patients also had a pancreatic endocrine tumor. The observed genetic mutations in the PC patients were c.703G > A (p.E235K) in exon 4 and c.1378C > T (p.R460X) in exon 10. All 3 patients had recurrence of hypercalcemia, and 2 patients underwent reoperation; pathologic analysis revealed the presence of a hyperplastic gland, not tumor recurrence. No cases had distant metastasis.
  
  
  CONCLUSIONS
  This is the first report of APN in an MEN1 patient. Although rare, the presence of PC or APN in MEN1 is noteworthy because it affects the management if hypercalcemia recurs, possibly requiring an open approach rather than the minimally invasive techniques used in the reoperative setting for benign disease.
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Christakis
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Naifa L
authors.initials: NL
authors.lastname: Busaidy
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Cote
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.affiliation: Department of Clinical Cancer Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Hyde
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Silva Figueroa
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Lily Joy
authors.initials: LJ
authors.lastname: Kwatampora
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Callisia N
authors.initials: CN
authors.lastname: Clarke
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; The First Hospital of Jilin University, Hepatobiliary Pancreatic Surgical Department, Changchun, Jilin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: nperrier@mdanderson.org.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Perrier
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D010280:Parathyroid Glands / Q000473:pathology / Q000601:surgery; D010282:Parathyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D012189:Retrospective Studies
keywords: Hypercalcemia; Multiple endocrine neoplasia type 1 (MEN 1); Neoplasm; Parathyroid carcinoma; Parathyroid gland; Parathyroidectomy; Primary hyperparathyroidism