eMedicine Specialties > Pediatrics: General Medicine > Dermatology

Nevoid Basal Cell Carcinoma Syndrome: Treatment & Medication

Author: Benjamin Barankin, MD, FRCPC, Dermatologist, Private Practice, Toronto
Coauthor(s): Gary Goldenberg, MD, Assistant Professor of Dermatology, Director Dermatopathology Laboratory, University of Maryland School of Medicine; Gordon E Searles, OD, MD, FRCPC, FACP, Program Director, Clinical Assistant Professor, Department of Medicine, Division of Dermatology and Cutaneous Sciences, University of Alberta Hospital, Edmonton, Canada
Contributor Information and Disclosures

Updated: Mar 13, 2009

Treatment

Medical Care

  • Although radiation is sometimes used to treat basal cell carcinomas (BCCs) in other settings, it is not recommended in the setting of nevoid basal cell carcinoma syndrome (NBCCS) because patients tend to form new BCCs at sites of irradiation soon after exposure. Radiation is a common treatment for medulloblastomas and results in extensive and invasive BCCs in the radiation field. Thus, when possible, radiation therapy should be minimized or avoided because more invasive BCCs and other tumors may result following treatment.5
  • Management of superficial multicentric BCCs without follicular involvement can be achieved through total body application of topical 0.1% tretinoin cream and 5% 5-fluorouracil (5-FU) twice daily. Lesions around the eyes are treated with 5-fluorouracil only. Patients should be examined every 3 months, and lesions that are growing or invading should be excised or curetted.
  • Evidence has accumulated to support the use of topical imiquimod on superficial BCCs.6,7,8 One study in patients with nevoid basal cell carcinoma syndrome showed clearance of BCCs after treatment for 6-8 weeks. Other types of BCC do not appear to respond as well. Occlusion does not appear to affect the response rate.
  • Oral isotretinoin has shown some benefit.9 However, it is not approved by the US Food and Drug Administration (FDA) for use in nevoid basal cell carcinoma syndrome and carries risk of toxicity.
  • In adults, photodynamic therapy (PDT) has been beneficial in the treatment of BCCs (topical and systemic), with an average of a 95% complete tumor response rate; PDT is not recommended in children because of a poorer response rate and scarring.

Surgical Care

  • BCCs are treated with curettage/electrodesiccation, simple excision, or Mohs surgery, but, because of the frequency of lesions, patients are left with extensive scarring from surgical procedures.
  • Recently, ultrapulse carbon dioxide laser has been demonstrated to be effective in the treatment of small BCCs in low-risk areas in patients with nevoid basal cell carcinoma syndrome.
  • Odontogenic keratocysts require an average of 4 operations throughout a lifetime, although some individuals have experienced up to 28 surgical procedures. Odontogenic keratocysts must be aggressively treated to prevent a high recurrence rate of 6-60% and should be removed by experienced oral-maxillofacial surgeons or otolaryngologists.
  • Medulloblastomas require surgery, radiation, and chemotherapy.

Consultations

  • Geneticist
  • Dermatologist
  • Plastic surgeon
  • Oral surgeon
  • Neurosurgeon
  • Ophthalmologist
  • Radiation oncologist
  • Dentist

Medication

Medications are used for symptomatic patients, usually as a temporary measure, while patients await definitive treatment. New medical options, such as topical imiquimod and 5-aminolevulinic acid (ALA) photodynamic therapy, have increased and improved the armamentarium.

Keratolytics

Management of superficial multicentric basal cell carcinomas (BCCs) without follicular involvement can be achieved through total body application of topical 0.1% tretinoin cream and 5% fluorouracil once daily. Lesions around the eyes are treated with 5-fluorouracil only. Oral isotretinoin and etretinate have shown some marginal benefit, but they are not FDA approved for treatment of nevoid basal cell carcinoma syndrome (NBCCS) and carry risk of toxicity. More recently, topical imiquimod has shown benefit, as has photodynamic therapy.


Tretinoin (Avita, Retin-A)

Inhibits microcomedo formation and eliminates lesions present. Makes keratinocytes in sebaceous follicles less adherent and easier to remove.

Adult

0.01-0.1% applied topically qd

Pediatric

Apply as in adults

Toxicity increases with coadministration of benzoyl peroxide, salicylic acid, and resorcinol; avoid topical sulfur, resorcinol, salicylic acid, other keratolytics, abrasives, astringents, spices, and lime

Documented hypersensitivity; use on open skin surfaces; internal use

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Photosensitivity may occur with excessive sunlight exposure; caution in eczema; do not apply to mucous membranes, mouth, and angles of nose


Fluorouracil (Efudex, Fluoroplex)

Used topically for the management of superficial BCCs. Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid and inhibiting thymidylate synthetase and subsequently cell proliferation.

Adult

Only the 5% strength is recommended; apply around eyes qd for 10-14 d q60d

Pediatric

Apply as in adults

Documented hypersensitivity; potentially serious infections

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Incidence of inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction


Isotretinoin (Accutane)

PO agent that treats serious dermatologic conditions. Synthetic 13-cis isomer of the naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to vitamin A. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
Until recently, only female patients of childbearing age needed to sign an informed consent form before initiating therapy. Because of heightened awareness of the potential of this product to cause depression and suicide, all patients are required to sign informed consent forms.

Adult

1-2 mg/kg/d PO

Pediatric

0.5-1 mg/kg/d PO according to tolerance of dryness

Toxicity may occur with vitamin A coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; isotretinoin may reduce plasma levels of carbamazepine

Documented hypersensitivity; pregnancy or breastfeeding

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of acne lesions (excessive granulation with crusting) may occur; patients with diabetes mellitus may experience problems in controlling blood sugar; avoid exposure to UV light or sunlight until tolerance achieved; discontinue treatment if rectal bleeding, abdominal pain, or severe diarrhea occur; caution in hypertriglyceridemia, hypercholesterolemia, depression, or bipolar illness


Acitretin (Soriatane)

Retinoic acid analog similar in action to etretinate or isotretinoin. Etretinate is the main metabolite and has demonstrated clinical effects similar to those observed with etretinate (removed from US market). Available as 10-mg and 25-mg cap.

Adult

25 mg PO qd initially for 1 mo; titrate upward to 50 mg/d if tolerated

Pediatric

Not established; limited data suggest 0.3 mg/kg/d PO, round dose to the nearest cap combination

Increases toxicity of methotrexate (avoid concomitant use); interferes with effects of microdose progestin (ie, minipill); coadministration with alcohol may enhance synthesis of etretinate, which has much longer half-life than acitretin (>120 d)

Documented hypersensitivity; pregnancy

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Do not use in severe obesity; women of childbearing age must be capable of complying with effective contraceptive measures, continuing contraception is recommended for at least 3 y after stopping treatment with acitretin; etretinate may form from acitretin, which takes about 2-3 y to clear from the body; caution in impaired renal or liver function; perform AST, ALT, and LDH tests prior to initiation of acitretin therapy, at 1-wk to 2-wk intervals until stable, and thereafter at intervals as clinically indicated

Immune response modifiers

These agents regulate, adjust, or potentiate immune function.


Imiquimod cream (Aldara)

Induces secretion of interferon alpha and other cytokines. Mechanism of action is unknown.

Adult

Apply topically 3 times/wk hs; leave on skin for 6-10 h

Pediatric

Not established

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Often causes local skin reactions (eg, erythema, edema, induration, vesicles, erosion, ulceration, excoriation, flaking, scabbing); other adverse effects may include itching, burning, and hypopigmentation

Photosensitizing Agent, Topical

These agents are used with photodynamic therapy.


Aminolevulinic acid (Levulan Kerastick)

Topical solution used to treat nonhyperkeratotic actinic keratoses on face or scalp. Treatment is 2-stage process. Solution is first applied to lesions, followed 14-18 h later by blue light illumination using BLU-U Blue Light Photodynamic Therapy Illuminator.
ALA is precursor of protoporphyrin IX (PpIX) in heme synthesis. PpIX is a photosensitizer and, when accumulation occurs, produces a photodynamic reaction. Light absorption results in excited state of porphyrin molecule and singlet oxygen generation, which further reacts to form superoxide and hydroxyl radicals.

Adult

Apply solution to lesions, dabbing gently with wet applicator tip to uniformly wet lesion surface, including edges, without excess running or dripping; following approximately 1 h of application, use blue light, intense pulse light, or pulse-dye laser to activate

Pediatric

Not established

Coadministration with other drugs causing photosensitization (eg, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulfonamides, tetracyclines) may increase photosensitization

Documented hypersensitivity; cutaneous photosensitivity at wavelengths of 400-450 nm; porphyria or known allergies to porphyrins

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Do not wash actinic keratoses following solution application and prior to phototherapy; protect affected areas from sunlight prior to phototherapy; reduce light exposure if stinging or burning occurs; may cause lesions to scale or crust, itching, hypopigmentation or hyperpigmentation, or erosion

More on Nevoid Basal Cell Carcinoma Syndrome

Overview: Nevoid Basal Cell Carcinoma Syndrome
Differential Diagnoses & Workup: Nevoid Basal Cell Carcinoma Syndrome
Treatment & Medication: Nevoid Basal Cell Carcinoma Syndrome
Follow-up: Nevoid Basal Cell Carcinoma Syndrome
Multimedia: Nevoid Basal Cell Carcinoma Syndrome
References
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References

  1. Lo Muzio L. Nevoid basal cell carcinoma syndrome (Gorlin syndrome). Orphanet J Rare Dis. Nov 25 2008;3:32. [Medline].

  2. Yamamoto K, Yoshihashi H, Furuya N, et al. Further delineation of 9q22 deletion syndrome associated with basal cell nevus (Gorlin) syndrome: Report of two cases and review of the literature. Congenit Anom (Kyoto). Mar 2009;49(1):8-14. [Medline].

  3. Shanley S, Ratcliffe J, Hockey A, et al. Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. Am J Med Genet. Apr 15 1994;50(3):282-90. [Medline].

  4. Hall J, Johnston KA, McPhillips JP, et al. Nevoid basal cell carcinoma syndrome in a black child. J Am Acad Dermatol. Feb 1998;38(2 Pt 2):363-5. [Medline].

  5. Choudry Q, Patel HC, Gurusinghe NT, Evans DG. Radiation-induced brain tumours in nevoid basal cell carcinoma syndrome: implications for treatment and surveillance. Childs Nerv Syst. Sep 15 2006;[Medline].

  6. Sterry W, Ruzicka T, Herrera E, et al. Imiquimod 5% cream for the treatment of superficial and nodular basal cell carcinoma: randomized studies comparing low-frequency dosing with and without occlusion. Br J Dermatol. Dec 2002;147(6):1227-36. [Medline].

  7. Stockfleth E, Ulrich C, Hauschild A, et al. Successful treatment of basal cell carcinomas in a nevoid basal cell carcinoma syndrome with topical 5% imiquimod. Eur J Dermatol. 2002;12(6):569-72. [Medline].

  8. van der Geer S, Ostertag JU, Krekels GA. Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome. J Eur Acad Dermatol Venereol. Dec 19 2008;[Medline].

  9. Campbell RM, Digiovanna JJ. Skin cancer chemoprevention with systemic retinoids: an adjunct in the management of selected high-risk patients. Dermatol Ther. 2006;Sep-Oct;19(5):306-14. [Medline].

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  14. Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. Nov-Dec 2004;6(6):530-9. [Medline].

  15. Kimonis VE, Goldstein AM, Pastakia B, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet. Mar 31 1997;69(3):299-308. [Medline].

  16. Korczak JF, Brahim JS, DiGiovanna JJ, et al. Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: a rare case illustrating gene-environment interaction. Am J Med Genet. Mar 31 1997;69(3):309-14. [Medline].

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Further Reading

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Keywords

nevoid basal cell carcinoma syndrome, NBCCS, Gorlin syndrome, basal cell nevus syndrome, BCNS, Gorlin-Goltz syndrome, multiple basal cell nevi, PTCH gene, basal cell carcinoma, BCC, medulloblastomas, ovarian fibromas, fibrosarcomas, rhabdomyosarcomas, meningiomas, cardiac fibromas, jaw cysts, palmar pits, macrocephaly, jaw swelling, keratocysts, cleft palate, spina bifida occulta, pectus deformity, spinal abnormalities, hypogonadism, kidney anomalies, acromegaly, malocclusion

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Contributor Information and Disclosures

Author

Benjamin Barankin, MD, FRCPC, Dermatologist, Private Practice, Toronto
Benjamin Barankin, MD, FRCPC is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery, Canadian Dermatology Association, Canadian Medical Association, International Society of Dermatology, Ontario Medical Association, Royal College of Physicians and Surgeons of Canada, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Coauthor(s)

Gary Goldenberg, MD, Assistant Professor of Dermatology, Director Dermatopathology Laboratory, University of Maryland School of Medicine
Gary Goldenberg, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Graceway Pharmaceuticals LLC Consulting fee Consulting

Gordon E Searles, OD, MD, FRCPC, FACP, Program Director, Clinical Assistant Professor, Department of Medicine, Division of Dermatology and Cutaneous Sciences, University of Alberta Hospital, Edmonton, Canada
Gordon E Searles, OD, MD, FRCPC, FACP is a member of the following medical societies: Alberta Medical Association, American College of Physicians-American Society of Internal Medicine, Canadian Medical Association, College of Physicians and Surgeons of Alberta, Pacific Dermatologic Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Kevin P Connelly, DO, Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center
Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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