Neurosurgical implications of Carney complex

Watson, Joe C.; Stratakis, Constantine A.; Bryant-Greenwood, P. K.; Koch, Christian A.; Kirschner, Lawrence S.; Nguyên, Toàn; Carney, J. Aidan; Oldfield, Edward H.

doi:10.3171/jns.2000.92.3.0413

Cited by 92 publications

(60 citation statements)

References 48 publications

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“…Carney complex (CNC), a rare condition, has been described in about 500 people to date and is caused in more than 60% of the cases that meet diagnostic criteria by an inactivating mutation in the gene encoding protein kinase A (PKA) type 1A regulatory (R1α) subunit (PRKAR1A) at 17q22-24; a second, as yet uncharacterized, locus at 2p16 has also been implicated in some families [6,7]. The pituitary gland is frequently affected in CNC and the clinical features are reminiscent of McCune-Albright syndrome (MAS) [8][9][10][11]: despite frequent abnormalities of growth hormone (GH), insulinlike growth factor 1 (IGF-1), and prolactin (PRL) secretion, clinical acromegaly or significant hyperprolactinaemia and growing GH-or PRL-producing tumors are rare [12][13][14][15]. Mouse models of R1α deficiency have been created but they failed to reproduce a specific or a significant pituitary phenotype, although mild abnormalities were seen.…”

Section: Introductionmentioning

confidence: 99%

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Boikos

Stratakis

2006

Pituitary

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First described in the mid 80's, Carney Complex (CNC) is a rare, dominantly heritable disorder with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1). Pituitary tumors have been described in a number of patients with CNC; they present with elevated growth hormone (GH) levels and mild hyperprolactinemia. However, most patients with CNC have mild hypersomatomammotropinemia starting in adolescence; this is similar to the situation in MAS patients: in both disorders, pituitary hyperplasia appears to precede tumor development. Familial pituitary tumor syndromes such as CNC provide an important insight into the genetics and molecular pathology of pituitary and other endocrine tumors. Our understanding of these conditions is expanding rapidly due to the identification of the causative genes and the availability of murine disease models. The present report reviews the clinical findings related to pituitary tumor development among patients with CNC and provides an update on murine models of the complex.

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Section: Introductionmentioning

confidence: 99%

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Boikos

Stratakis

2006

Pituitary

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“…In these cases, biochemical abnormalities of GH and PRL secretion were present in advance of radiological detection of the tumor [9,10]. The incidence of GH-producing pituitary tumors in CNC has been estimated at less than 15% [1,6,11], whereas GH "paradoxical" responses to various stimuli [such as to thyrotropin-releasing hormone (TRH)] or IGF-I elevation, without a detectable tumor,maybe present in up to 80% of affected patients [25]. The finding of probable hyperplasia in pituitary tissue from patients with CNC, who underwent TSS for acromegaly, is consistent with these clinical observations.…”

Section: Overviewmentioning

confidence: 99%

“…Although growth hormone (GH) and prolactin (PRL) secretion are frequently abnormal in affected patients [9,10], clinical acromegaly or significant hyperprolactinemia and GH-or PRL-producing tumors, respectively, have been detected in less than one fifth of them [11,12]. The pattern of biochemical abnormalities of GH and PRL secretion without pituitary tumors that are detectable by common imaging modalities, and infrequent development of clinically significant acromegaly is reminiscent of the situation in McCune-Albright syndrome (MAS) [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Pituitary Pathology in Carney Complex Patients

et al. 2004

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Carney complex (CNC) is a familial multiple neoplasia syndrome with features overlapping those of McCune-Albright syndrome (MAS) and multiple endocrine neoplasia (MEN) type 1 (MEN 1). Like MAS and MEN 1 patients, patients with CNC develop growth hormone (GH)-producing pituitary tumors. Occasionally, these tumors are also prolactin-producing, but there are no isolated pro-lactinomas or other types of pituitary tumors. In at least some patients with CNC, the pituitary gland is characterized by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only. Hyperplasia most likely precedes the formation of GH-producing adenomas in CNC, as has been suggested in MAS-related somatotropinomas, but has never been seen in MEN 1 patients. In at least one case of a patient with CNC and advanced acromegaly, a GH-producing macroadenoma showed extensive genetic changes at the chromosomal level. So far, half of the patients with CNC have germline inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss-of-hererozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1α of the cAMP-dependent protein kinase A (PKA) may act as a tumor-suppressor gene in CNC somatomammotrophs. These data provide evidence for a PRKAR1A-induced somatomammotroph hyperpasia in the pituitary tissue of CNC patients; hyperplasia, in turn may lead to additional genetic changes at the somatic level, which then cause the formation of adenomas in some, but not all, patients.

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“…It was previously thought that melanotic schwannomas were benign lesions, but metastases can arise from sporadic melanotic schwannomas as well as from the PMS associated with Carney complex. 16 Peripheral nerve tumors are among the most diverse of all soft-tissue tumors, both in terms of clinical behavior and histological features. In the past, because there were no precise pathological definitions of the principal types of peripheral nerve tumors, physicians were prevented from offering consistent advice about appropriate treatment.…”

Section: Discussionmentioning

confidence: 99%

Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma?

Sengoz

Taşdemiroğlu²,

Togay³

2006

FOC

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✓The authors present a case of clear cell sarcoma (CCS) in which the tumor originated in the S-1 nerve root and had been previously diagnosed as psammomatous melanotic schwannoma (PMS). This is the third case of a spinal nerve root origin for CCS reported in the English-language literature. The similar histogenesis of CCS and malignant melanoma supports the hypothesis that biological agents or immunotherapy are potentially important areas of investigation. The patient underwent S1–3 laminectomy and gross-total resection of the mass lesion. The border of the resection was extended 1 cm distal to the tumor margin. The postoperative period was uneventful. The new histopathological diagnosis was CCS (malignant melanoma of soft tissue). Despite total resection, the patient returned with disseminated disease at the 18-month follow-up visit. His follow-up magnetic resonance image of the lumbar spine revealed sacral L5–S3 involvement of the vertebral bodies along with disseminated cauda equina seeding. A CCS originating from peripheral nerves is quite rare. The histopathological and immunohistochemical appearance of CCSs resembles those of PMSs. Surgery should be the first choice of treatment.

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Neurosurgical implications of Carney complex

Cited by 92 publications

References 48 publications

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Pituitary Pathology in Carney Complex Patients

Is clear cell sarcoma a malignant form of psammomatous melanotic schwannoma?

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