Article

Silent familial isolated pituitary adenomas: histopathological and clinical case report.

Department of Human and Hereditary Pathology, S. Matteo IRCCS Foundation, University of Pavia, Pavia, Italy.
Endocrine Pathology (Impact Factor: 1.64). 04/2008; 19(1):40-6. DOI: 10.1007/s12022-008-9018-2
Source: PubMed

ABSTRACT Familial isolated pituitary adenoma (FIPA) is a rare condition independent of Carney Complex or MEN1. An international multicenter study recently described 28 nonfunctioning pituitary adenomas in 26 families with only two homogeneous nonsecreting phenotype families consistent of silent GH and silent gonadotroph adenomas, respectively. We present the clinical, genetic, and morphological analysis of two silent pituitary adenomas occurring in a man and his daughter, and discuss the differential diagnosis associated with their histological, immunohistochemical, and ultrastructural features. The patients developed invasive nonsecreting macroadenomas manifesting only with compressive symptoms. Genetic analysis in the father showed no MEN-1 germ-line mutation. Tissue samples obtained after paraseptal trans-sphenoidal surgery were studied by immunohistochemistry for adenohypophyseal hormones, low molecular weight cytokeratins (CAM 5.2), proliferation markers, and anterior pituitary transcription factors (Pit-1 and SF-1) and by electron microscopy for secretory granules. The clinical, histological, and immunohistochemical features of the lesions posed a differential diagnosis between a null cell adenoma and a silent corticotroph adenoma (Type II); on the basis of immunohistochemical stains for cytokeratin and adenohypophysis cell lineage markers, tumor behavior and ultrastructural studies we concluded for the second. The reported cases represent an as yet undescribed example of homogeneous family with silent corticotroph adenomas (Type II). Our observations support the trend for more aggressive behavior in nonsecreting FIPAs as compared with sporadic adenomas.

Download full-text

Full-text

Available from: Alberto Falchetti, Dec 30, 2013
0 Followers
 · 
135 Views
 · 
41 Downloads
  • Source
    • "An ultrastructural study was performed as described previously (Villa et al. 2008), which was limited by the formalin-fixing and paraffin-embedding protocol to the evaluation of secretory granule diameter and cytoplasmic distribution (for detailed discussion of ultrastructural findings in AIP-mutated pituitary adenomas , see Leontiou et al. (2008)). Before tissue microdissection was performed, normal, adenomatous, and hyperplastic pituitary tissues were identified using reticulin staining. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.
    Endocrine Related Cancer 03/2011; 18(3):347-56. DOI:10.1530/ERC-11-0059 · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinically-relevant pituitary adenomas occur with a prevalence of approximately 1 per 1000 population in Belgium. Pituitary adenomas that occur in families are likely to have an important genetic pathophysiological basis. Currently about 5% of all pituitary adenoma cases have a family history of pituitary adenomas, classically due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Over the last decade we have described non-MEN1/CNC familial pituitary tumours that include all tumour phenotypes, a condition named 'familial isolated pituitary adenoma' (FIPA). Clinical features of FIPA differ from those of sporadic pituitary adenomas in that patients with FIPA are often younger and have larger tumours at diagnosis. Approximately 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. In this review we examine new findings on the epidemiology of pituitary adenomas and we review familial causes of pituitary adenomas with a particular emphasis on modern clinical testing. In addition, the clinical and genetic features of FIPA are described as FIPA represents a useful framework to study the features of pituitary adenomas that occur in a familial setting.
    Acta clinica Belgica 11/2008; 63(6):418-24. DOI:10.1179/acb.2008.086 · 0.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Pituitary adenomas occur in a familial setting in about 5% of all cases and over half of these are due to multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Since the late 1990s, we have described non-MEN1/CNC familial pituitary tumors that include all tumor phenotypes and have named this condition 'familial isolated pituitary adenoma' (FIPA). Clinical features of FIPA differ from those of sporadic pituitary adenomas in that patients with FIPA are often younger and have larger tumors at diagnosis. About 15% of FIPA patients have mutations in the aryl hydrocarbon receptor interacting protein gene (AIP), which indicates that FIPA may have a diverse genetic pathophysiology. We review the clinical features of FIPA, the tumor pathologies found in this setting and the genetic/molecular data that have been recently reported. CONCLUSIONS: Clinically relevant pituitary adenomas are more common than previously thought and occur in a familial setting in about 5% of cases overall. Therefore, specific questioning regarding family history of pituitary disease should be part of the workup of all patients with pituitary adenomas, not just those with acromegaly. FIPA is a useful clinical framework to study the features of pituitary adenomas that occur in a familial setting since it encompasses all tumor phenotypes and heterogeneous/homogeneous expression among affected family members.
    Hormone Research 02/2009; 71 Suppl 1:105-11. DOI:10.1159/000178050 · 2.48 Impact Factor
Show more