Inherited disorder characterized by numerous cutaneous
malignant melanomas associated with tumors of the nervous system, including
astrocytoma, medulloblastoma, glioblastoma multiforme, ependymoma, glioma,
meningioma, and acoustic neurilemmoma.
Melanoma and Neural System Tumor Syndrome.
Autosomal dominant. The gene has been mapped
to 9p21 with germ-like mutation in the cyclin-dependent kinase inhibitor 2A
Chromosome region 9p21 is involved in chromosomal
inversions, translocations, heterozygous deletions, and homozygous deletions
in a variety of malignant cell lines. These findings suggest that 9p21
contains a tumor suppressor locus that may be involved in the genesis of
several tumor types.
Clinical predictive genetic testing for mutation in the
CDKN2A gene is available commercially.
Generally, most individuals affected with this
syndrome present with more nevi than normal, and the tendency to dysplastic
transformation is significantly higher. The association with neural tumor
may be higher, and more pancreatic cancers are associated.
Anesthetic considerations will be
determined by the presence of brain tumor and its type. Raised intracranial
pressure, vascularization (e.g., medulloblastoma), and seizures. Anesthesia
may be challenging when isolated limb perfusion is indicated to prevent
cardiovascular instability, called “distributive shock", which is
caused by the injection of tumor necrosis factor.
No known specific implications with
All of the following conditions
are allelic variants of CDKN2A mutation.
Melanoma-Pancreatic Cancer Syndrome: Atypical familial multiple
mole that can be caused by mutations in the gene encoding cyclin-dependent
kinase inhibitor-2A (CDKN2A). Standard anesthetic considerations.
Cutaneous Malignant Melanoma: Mostly associated with fair
complexion, blue eyes, multiple ephelides, and familial history of melanoma.
Li-Fraumeni Syndrome (LFS): Childhood sarcoma that usually is family
related. This association often involves brain tumors, osteosarcoma,
leukemia, and adrenocortical carcinoma. Precautions before anesthesia should
include proper evaluation of intracranial pathology, intracranial pressure,
and cortisol functions.
Fraser M, Marentay P, Bertha R: A collaborative approach to isolated limb
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Greene MH: The genetics of hereditary melanoma and nevi. 1998 Update.
Cancer 86(11 suppl):2464, 1999.