title: Malignant prolactinoma with extracranial metastases: a report of three cases.
abstract: OBJECTIVE
  Prolactin-secreting tumours of the pituitary almost never metastasize extracranially. However, we have recently seen three such patients, whose presentation, clinical course and response to treatment are reviewed in order to determine whether they possess unique clinical features, and to assess optimum therapy.
  
  
  METHODS
  Three patients with extracranial metastases from prolactinomas have been retrospectively reviewed.
  
  
  METHODS
  Clinical courses, biochemical parameters and imaging modalities (CT, MR and radiolabelled somatostatin analogue scanning) and histopathology were assessed before and during different therapeutic regimens.
  
  
  RESULTS
  All three patients' presentations were initially unremarkable, but later each had persistent and relentlessly increasing serum prolactin concentrations and evidence of distant spread of their tumours. The first patient presented aged 32 and was treated with repeated transsphenoidal resections of the tumour, pituitary radiotherapy, high dose bromocriptine therapy, the somatostatin analogue octreotide and chemotherapy. Nine years after the original diagnosis a liver biopsy revealed carcinoma cells positively immunostaining for prolactin. At autopsy further microscopically similar metastases were seen in both lungs and the left hilar lymph nodes. The second patient presented aged 48 and was treated with external beam pituitary radiotherapy, bromocriptine, transsphenoidal hypophysectomy and chemotherapy. Fifteen years after the original diagnosis bone biopsy revealed carcinoma cells positively immunostaining for prolactin; the patient developed interstitial nephritis and died in renal failure. The third patient presented aged 48 with hypogonadism and bitemporal hemianopia due to a macroadenoma. This was removed transfrontally and followed by external beam radiotherapy. After recurrence, further surgery and radiotherapy were undertaken, but the tumour continued to grow and the patient died suddenly of a pulmonary embolus. At autopsy, tumour was found in thoracic lymph nodes and lung capillaries.
  
  
  CONCLUSIONS
  These three patients may be added to the previous two reported cases of malignant prolactinoma with extracranial spread. Several different therapies were tried but were of limited value in controlling the progression of the disease, although chemotherapy is an important modality to be considered. No particular factor or combination of factors at presentation differentiated these patients from more typical patients whose disease is much less aggressive.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, West Smithfield, London, UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Walker
authors.forename: A
authors.initials: A
authors.lastname: Grossman
authors.forename: J V
authors.initials: JV
authors.lastname: Anderson
authors.forename: E
authors.initials: E
authors.lastname: Ur
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: J
authors.initials: J
authors.lastname: Benn
authors.forename: C
authors.initials: C
authors.lastname: Lowy
authors.forename: P H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: P N
authors.initials: PN
authors.lastname: Plowman
authors.forename: D G
authors.initials: DG
authors.lastname: Lowe
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D008577:Meningeal Neoplasms / Q000556:secondary; D008579:Meningioma / Q000556:secondary; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000473:pathology*; D015175:Prolactinoma / Q000556:secondary*