In CALMs of NF1 patients, giant melanin granules (macromelanosomes) are present in melanocytes.
Correspondence: Dr M Kiuru, MD, Ph D, Departments of Dermatology and Pathology, University of California Davis, 3301 C Street, Suite 1450, Sacramento, CA 95816, USA.
E-mail: [email protected] 10 September 2016; Revised 10 November 2016; Accepted 29 November 2016Advance online publication 9 January 2017MAPK pathway is critical in melanoma.
These include cafe-au-lait-macules, axillary and inguinal freckling, neurofibromas, and plexiform neurofibromas, present in 90Café-au-lait macules (CALMs) are tan to brown sharply demarcated, uniformly pigmented macules or patches typically on the trunk and extremities.
In NF1, CALMs are the earliest manifestation, typically appearing at 0–3 years of age.
Other reported neoplasms include juvenile myelomonocytic leukemia, pheochromocytoma, central nervous system tumors other than optic glioma, rhabdomyosarcoma, duodenal carcinoid, somatostatinoma, parathyroid adenoma, and gastrointestinal stromal tumor (Table 1b). Epidemiologic studies have also shown an increased risk of cancer of the esophagus, stomach, colon, liver, lung, bone, thyroid, and ovary, non-Hodgkin’s lymphoma, and chronic myeloid leukemia. The NF1 gene at 17q11.2 is now known to consist of 60 exons and to generate several alternatively spliced isoforms.
Although identification of mutations in NF1 has been challenging due to the very large size and complexity of the gene, lack of mutational hot spots, and the presence of pseudogenes, hundreds of mutations have been reported.
of NF1 patients, with a peak incidence in young adults.
Rapid growth, increased pain or a new neurologic deficit may be a sign of malignant transformation of a pre-existing plexiform neurofibroma in NF1 patients.
Additionally, NF1 mutations characterize certain clinicopathologic melanoma subtypes, specifically desmoplastic melanoma.
This review discusses the current knowledge of the NF1 gene and neurofibromin 1 in neurofibromatosis type I and in melanoma.
Melanoma can be grouped into four molecular subtypes based on their main genetic driver: BRAF-mutant, NRAS-mutant, NF1-mutant, and triple wild-type tumors.