Nevoid Basal Cell Carcinoma Syndrome (Basal Cell Nevus Syndrome) Treatment & Management

Updated: Jun 14, 2021
  • Author: Daniel Berg, MD; Chief Editor: Dirk M Elston, MD  more...
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Approach Considerations

Treatment of patients with nevoid basal cell carcinoma syndrome (NBCCS) involves surveillance for and treatment of the associated findings. Because most of the findings involve tumors (benign and malignant), treatment is often surgical.

Go to Basal Cell Carcinoma for more complete information on this topic.


Pharmacologic Therapy

Topical agents such as imiquimod [26] and 5-fluorouracil are available and have been approved for treatment of basal cell carcinoma (BCC) in the United States. These medications have a lower cure rate than surgical therapy but may be a useful adjunct in patients with multiple lesions and may help play a chemopreventative role in the development of new BCCs. [27] Despite the lower cure rate (which may reach up to 80% for superficial BCCs with imiquimod), these agents may play a useful role in allowing patients to treat their own selected smaller lesions, especially superficial BCCs on the trunk and extremities. In general, such medications should be considered best for use in smaller or more superficial lesions, away from critical anatomic sites. Although no guidelines for treatment of pediatric basal cell nevus syndrome (BCNS) exist, small series suggest that less invasive treatment like the topical medications noted above, cryotherapy with liquid nitrogen, and touch electrodessication are effective and well tolerated. [23]

Investigations and clinical trials are evaluating topical photodynamic therapy, which is approved in the United States only for the treatment of actinic keratosis. Topical photodynamic therapy may be a useful treatment for multiple BCCs in patients with nevoid basal cell carcinoma syndrome (NBCCS). This therapy consists of an application of a commercially available topical agent (either aminolevulinic acid [ALA] or methyl-ALA), followed by treatment with an appropriate visible light (typically blue or red light), which causes tumor destruction by a photo-induced reaction. [28, 29]

Topical itraconazole has been investigated in BCNS patients. It is safe and associated with intratumor drug concentration, but it did not shrink the tumor area. [30]

Other novel agents, such as the relatively newly developed hedgehog (HH) inhibitors, are oral medications. [6] In 2012, vismodegib, a small-molecule inhibitor of the HH pathway, was approved by the US Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic BCC, and sonidegib was approved in the summer of 2015 for locally advanced BCC. [31] There is not yet a specific FDA approval for the use of either drug in NBCSS, although a randomized, placebo-controlled, phase 2 trial of 42 NBCSS patients from 2012 treated with vismodegib showed a 70% reduction in the number of new surgically eligible tumors and a decrease in the size of many existing tumors, sometimes dramatically. [32] This and other studies show that tumors tend to recur following cessation of treatment, [32, 33] and a significant number of patients have treatment-limiting adverse effects. [32, 34, 35]

Similar findings were reported in 2016 in a study of vismodegib in patients with NBCSS. [36] In this study, further information was gleaned, including that hair regrowth may be incomplete after longer treatment. This study also did not find resistance to vismodegib (seen more commonly in patients treated for advanced BCC) in NBCSS patients, who appear to remain sensitive to vismodegib with intermittent treatment.

A 2017 study of patients with multiple BCCs, including patients with NBCSS, used intermittent therapy with vismodegib. [37] These trials suggest that intermittent therapy with planned breaks may be useful for reducing the size of existing BCCs and the number of new BCCs in these patients, with fewer adverse effects than with continuous therapy. This suggests that intermittent therapy may be an alternative dosing strategy for patients with NBCSS that can allow them to remain on the medication and maintain its benefits. This is particularly important given that in the 2016 study of vismodegib in patients with NBCSS, only 17% were able to tolerate continuous therapy for 36 months. [38] Newer data of various drug holiday regimens have shown similar results, with reduced adverse effects but similar efficacy to daily dosing. Regimens include weekday dosing with weekends off, [39, 40] and 8- and 12-week drug holidays with various lengths of initiation phases. [39, 41]

Resistance of individual BCCs has been well described but appears much less frequent in patients with BCNS compared with patients with locally advanced BCC. A 2018 study of resistant tumors in a patient with BCNS identified smoothened mutations in resistant BCCs. [42]

Surgical treatment of individual resistant tumors may often still be possible for patients who remain on therapy.


Excision of Tumors

Oral surgery involving cyst enucleation followed by mechanical curettage or use of peripheral ostectomy may be required for odontogenic keratocysts. The incidence of recurrence following treatment is high.

For BCCs, early detection and treatment are critical to prevent any individual lesion from becoming invasive. Avoidance of radiation is an important principle based on several reports of BCCs developing in radiated fields. Surgical methods include electrodesiccation and curettage (ED&C), simple excision, and Mohs micrographic surgery.

Because of the large number of tumors expected over a lifetime, surgical methods should be chosen with attention given to cure rate and scarring potential. Less invasive approaches should be considered for small tumors, and these include topical therapies as well as curettage rather than excision. Similarly, reconstruction after tumor removal should take into account the likelihood of further BCCs in the vicinity and should be kept simple whenever possible (eg, second intention healing or primary closure vs use of flaps).

Of note, the small acrochordonlike, flesh-colored papules commonly seen on the upper trunk and neck seen more commonly in children and teens are usually slowly growing and can often be treated conservatively (eg, with light electrosurgery) rather than with potentially more disfiguring excision.

Surgery for ovarian tumors or cardiac tumors may be required for either treatment or prevention of symptoms.



A dermatologist should maintain ongoing surveillance and treatment of skin cancer. Frequent visits (sometimes as often as every 2-3 mo) are recommended to identify and to treat lesions when they are as small as possible.

A genetic counselor is a very important component of the ongoing care of the patient, particularly regarding issues of having children, but also to help determine if other family members are at risk of having the syndrome. As new research is performed, the availability, sensitivity, and specificity of molecular testing may change.

Other specialists may be needed to (1) assess a newly diagnosed individual and (2) help manage associated abnormalities if they develop, including a neurologist, neurosurgeon, pediatrician, cardiologist, cardiac surgeon, gynecologist, dentist, oral surgeon, plastic surgeon, and ophthalmologist.


Long-Term Monitoring

Ongoing surveillance and treatment for sequelae of nevoid basal cell carcinoma syndrome (NBCCS) is required. In addition, in family members of patients with NBCCS in whom the diagnosis is possible but not confirmed, ongoing follow-up to help detect diagnostic criteria may be important.

BCCs require frequent follow-up care, 3-4 times a year (or more), to achieve early diagnosis and treatment. Odontogenic keratocysts require dental follow-up visits, including periodic radiographic evaluation, especially in childhood and early adolescence.

Screening for cardiac fibromas with echocardiography should be considered in infants with the syndrome and then if symptoms suggest their presence. Ovarian fibromas can be visualized on a peripubertal ultrasound as a baseline and then can be considered if symptoms develop.

In young children at risk, medulloblastomas necessitate a neurologic examination every 6 months; annual MRIs should be considered in children younger than 7 years.