Familial atypical multiple mole melanoma (FAMMM) syndrome)





It is inherited as an autosomal dominant manner with incomplete penetrance. 



FAMMM syndrome has been associated with mutations in the 16p locus of CDKN2A (9p21), a tumor suppressor gene involved in cell cycle inhibition. 



Approximately 60% of patients with FAMMM syndrome do not have a CDKN2A mutation.



Often greater than  50 melanocytic nevi.


FAMMM most often presents in children and teenagers but can occur at any age. 


The majority of nevi will be clinically typical but some may have an atypical appearance.


Atypical  melanocytic nevi are, raised, and/or have different shades of tan, brown, black, or red and often of different sizes, and resemble  early melanoma.


Most lesions occur on the back, chest, buttocks, breasts, and scalp. 


Melanomas can arise from such atypical moles or de novo and have been reported in some FAMMM syndrome patients as early as the second to third decade of life. 


Those with CDNK2A mutations have a 90% risk of developing melanoma by the age of 80.


Those with CDNK2A mutations have a 20% increased risk of developing pancreatic cancer by the age of 75. 



CDNK2A mutations are also associated with a younger age of onset of disease.



Other cancers associated with FAMMM syndrome include breast cancer, esophageal cancer and sarcoma, rarely.



Diagnostic criteria: high total body nevi count (usually >50), 


nevi with lentiginous pattern, nuclear atypia and melanomas in 1 or more first or second degree relatives. 



Nevi are evaluated for melanoma based on the  characteristics of asymmetry, border irregularity, color variation, diameter >6 mm, and evolution or elevation (ABCDE ).



Molecular genetic testing identifying a CDKN2A mutation confirms diagnosis.



The  absence of CDKN2A mutation in does not exclude the diagnosis of FAMMM syndrome.



Differential diagnoses:  cutaneous neurofibromas and pancreatic ductal adenocarcinoma as well as Neurofibromatosis type 1.



Patients with a FAMMM  syndrome should begin screening at age 10 and includes a total body skin examination with the use of dermoscopy. 



Clinical self-exams should then be performed every 6 months to monitor any changes in nevi. 



In families with a history of pancreatic cancer or a CDKN2A mutation, screening abdominal CT or  magnetic resonance imaging, or endoscopic ultrasound can be initiated  starting at age 40. 




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