Basal Cell Nevus Syndrome: Guidelines for Early Detection

GEORGE J. BITAR, M.D., Fairfax, Virginia
CHARLES K. HERMAN, M.D., Albert Einstein College of Medicine, Bronx, New York
MOHAMMED I. DAHMAN, M.D., Ain Shams University, Cairo, Egypt
MARTIN A. HOARD, M.D., University of Virginia, Charlottesville, Virginia

Basal cell nevus syndrome is an autosomal dominant condition with complete penetrance and variable expressivity. It is characterized by five major components, including multiple nevoid basal cell carcinomas, jaw cysts, congenital skeletal abnormalities, ectopic calcifications, and plantar or palmar pits. Other features include a host of benign tumors, ocular defects, and cleft lip and palate. Guidelines for diagnosis include a family history, careful oral and skin examinations, chest and skull radiographs, panoramic radiographs of the jaw, magnetic resonance imaging of the brain, and pelvic ultrasonography in women. (Am Fam Physician 2002;65:2501-4. Copyright© 2002 American Academy of Family Physicians.)

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Basal cell nevus syndrome, also known as Gorlin's syndrome, was first reported by Jarisch and White in 1894. The spectrum of disease associated with this syndrome was described in detail by Gorlin in 1960.¹ The prevalence is estimated to be 1 per 60,000 persons.² This syndrome is characterized by five major components as well as other features that may be present (Table 1).^3,4 Basal cell nevus syndrome is an autosomal dominant condition with complete penetrance and variable expressivity.^5,6 The gene responsible has been localized to chromosome 9q22.1-q31.^7,8

TABLE 1 Clinical Features Associated with Basal Cell Nevus Syndrome Clinical features Percentage of patients affected Multiple nevoid basal cell carcinomata3 50 Odontogenic keratocysts (jaw cysts are the earliest presenting sign) 65 to 70 Congenital skeletal abnormalities 65 to 70  Bifid ribs    Synostosis    Frontal and parietal bossing    Hypertelorism    Sprengal's deformity (high scapulae)   Ectopic calcification of the falx cerebri 65 to 70 Plantar and/or palmar pits4 60 Other features Varies  Neoplasms and hamartomas     Medulloblastomas     Myocardial fibromas     Meningiomas     Ovarian fibromas     Rhabdomyomas     Lymphomesenteric cysts    Ocular defects     Colobomas     Cataracts     Glaucoma    Cleft lip and palate   Information from references 3 and 4.

TABLE 2 Diagnostic Tests in the Illustrative Case Radiologic diagnosis Examples Skull radiograph Calcified falx cerebri (see Figure 3) Panoramic films* Right mandibular ramus odontogenic cyst measuring 6 3 2.5 cm displacing the embedded lower left third molar   Right mandibular body odontogenic cyst measuring 2.5 3 1.5 cm diverting the roots of the lower left second tricuspid and the lower left first molar   Odontogenic cyst around the crown of the impacted upper right third molar   Right maxillary cystic lesion with a 3-cm diameter associated with the imbedded left upper third molar (see Figure 4) Computed tomography Confirmed the panoramic radiographic findings scan Chest radiograph Showed rib asymmetry, especially of the second and third ribs   No bifid ribs were found *--Annual panoramic films planned for the follow-up care.

The patient described in the following illustrative case was not diagnosed for several years, despite an array of physical signs and symptoms. Increased awareness on the part of the family physician could have led to earlier referral for specialized diagnosis and treatment. Early diagnosis and treatment may reduce the severity of the long-term sequelae of basal cell nevus syndrome, including malignancy and oromaxillofacial deformation and destruction.

Illustrative Case

A 15-year-old female with complaints of increasing facial swelling of the mandibular and maxillary regions presented to a plastic surgery clinic after referral from her primary care physician. The swelling had persisted for several years despite conservative treatment with anti-inflammatory agents. The patient's past medical history was significant for multiple cutaneous cystic lesions on the face, chest, and back that necessitated several surgical excisions during the past several years; severe amblyopia; asthma; and recurrent urinary tract infections. The patient was adopted, and her family history is unknown.

FIGURE 1. Preoperative anterior photograph showing multiple areas of swelling in the mandibular and maxillary regions, missing the upper left and right lateral incisors, multiple cutaneous nevi, and bifrontal bossing.

FIGURE 2. Preoperative right lateral photograph showing multiple areas of swelling in the mandibular and maxillary regions and multiple cutaneous nevi.

On physical examination, multiple facial cutaneous nevi were evident, with marked bifrontal bossing. Multiple areas of swelling were noticeable in the mandibular and maxillary regions (Figures 1 and 2). An expansile lesion of the right mandibular cortex was visualized and palpated, as well as a right maxillary expansile lesion. The upper left and right lateral incisors were missing. Palpation of the areas of swelling did not produce pain, nor was any erythema present.

FIGURE 3. Skull radiograph showing a calcified falx cerebri.

FIGURE 4. Panorex film showing a right mandibular ramus cyst, right mandibular body cystic lesion, and right maxillary cystic lesion.

Diagnostic tests included skull and chest radiographs, panoramic films, and computed tomographic scans (Table 2).

Under general anesthesia, the patient underwent excision of all odontogenic cysts with extraction of all four third molars (Figures 5 and 6). The right infraorbital, lingual, and mental nerves were visualized during the surgery. The excised jaw cysts were diagnosed as odontogenic keratocysts by histopathologic examination.

FIGURE 5. Intraoperative photograph in which the right maxillary cyst can be clearly visualized.

FIGURE 6. Intraoperative photograph of right mandibular body cyst.

The patient's postoperative course was unremarkable, and she recovered well. She is being monitored closely for nevi and jaw cyst recurrence with biannual follow-up examinations and annual panoramic films. No recurrence has been detected in the 10 months following her surgery.

Clinical Presentation

The presence of multiple odontogenic cysts, calcified falx cerebri, and multiple cutaneous nevi establishes a diagnosis of basal cell nevus syndrome.

The presence of multiple odontogenic cysts, a calcified falx cerebri, and multiple cutaneous nevi establishes a diagnosis of basal cell nevus syndrome. The presenting sign of increasing facial swelling results from expansion of the cystic lesions on the jaw. Odontogenic keratocysts are cystic lesions lined with keratinized epithelium. Most authors identify the dental lamina as the origin of the cysts.

Cysts most frequently occur in the molar-ramus region of the mandible, but they may also occur in the maxilla.⁹ Cyst development may occur in patients as young as four years.¹⁰ These cysts have a proclivity for local invasion, including involvement of the teeth, and they have a tendency to recur. A recurrence rate of 60 percent in patients with basal cell nevus syndrome has been documented.¹¹ Recurrence is the consequence of incomplete removal, remnants of dental lamina within the jaw, or the presence of satellite cysts. Therefore, treatment consists of wide surgical excision and curettage with extraction of associated teeth. Bone grafting and alveolar nerve grafting may be required in some instances.

Histopathologic examination of excised tissue is required because several cases of malignant transformation to squamous cell carcinoma have been reported in the literature.¹² Close follow-up of these patients is necessary to monitor for recurrence of odontogenic keratocysts and the development of basal cell carcinoma of the skin. Biannual physical examinations and annual panoramic films are recommended.

Role of the Family Physician

Appropriate imaging studies in the diagnosis of basal cell nevus syndrome include chest and skull radiographs, panoramic films, magnetic resonance imaging of the brain, and pelvic ultrasonography in women.

The family physician's role in treating patients with basal cell nevus syndrome is threefold. First, the physician should recognize the syndrome by the history and physical examination and be alerted to the other findings that may coexist. The history should include relevant medical and dental information, including removal of jaw cysts, abscesses, or skin lesions. Any relevant family history, including brain tumors or female-organ tumors, should be ascertained.

The physical examination should include an oral inspection for mandibular and maxillary swelling, head circumference and head shape inspection, skin examination for basal cell nevi, and pits on the palms and soles. The necessary radiographic studies, such as chest and skull radiographs and panoramic films, should be obtained early in the treatment process to confirm the syndrome and establish a clear treatment plan. A magnetic resonance image of the brain would be important to detect meningiomas or medulloblastomas at an early age. Medulloblastomas can be detected between two and three years of age and may be treated with radiotherapy. Ovarian ultrasonography for detection of ovarian cysts or fibromas is also indicated.

The second task is to alert family members to be tested for the syndrome, because it is an autosomal dominant disorder that has been identified in families.^6-8 Finally, the patient should be referred to the appropriate subspecialists, including a neurosurgeon, plastic surgeon, or obstetrician, depending on the specific manifestations that need to be addressed.

The authors indicate that they do not have any conflicts of interest. Sources of funding: none reported.

This article exemplifies the AAFP 2002 Annual Clinical Focus on cancer: prevention, detection, management, support, and survival.

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The Authors

GEORGE J. BITAR, M.D., is currently in private practice in cosmetic and hair transplantation in Fairfax, Va.

CHARLES K. HERMAN, M.D., is a resident in the Department of Plastic Surgery at Albert Einstein College of Medicine, Bronx, N.Y.

MOHAMMED I. DAHMAN, M.D., is a visiting physician from Ain Shams University, Cairo, Egypt.

MARTIN A. HOARD, M.D., is assistant professor in the Department of Plastic Surgery at the University of Virginia, Charlottesville.

Address correspondence to George J. Bitar, M.D., Prosperity Medical Plaza, 8503 Arlington Blvd., Suite 130, Fairfax, VA 22031 (e-mail: GBITAR007@aol.com). Reprints are not available from the authors.

REFERENCES

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3. Kakascik GE, LoVerme SR, Tutela RR. Multiple nevoid basal cell carcinoma syndrome. Am Surg 1977;43:617-20.
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5. Bare JW, Chen MA, Rothman AL, Epstein EH. Basal cell nevus syndrome: linkage studies at 9q. The American Society of Human Genetics 42nd annual meeting. Am J Hum Genet 1992;51(4 suppl):A57-62.
6. Bonifas JM, Bare JW, Kerschmann RL, Master SP, Epstein EH Jr. Parental origin of chromosome 9q22.3-q31 lost in basal cell carcinomas from basal cell nevus syndrome patients. Hum Mol Genet 1994;3:477-8.
7. Farndon PA, Del Mastro RG, Evans DG, Kilpatrick MW. Location of gene for Gorlin syndrome. Lancet 1992;339:581-2.
8. Compton JG, Goldstein AM, Turner M, Bale AE, Kearns KS, McBride OW, et al. Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q. J Invest Dermatol 1994;103:178-81.
9. Lo Muzio L, Nocini PF, Savoia A, Consolo U, Procaccini M, Zelante L, et al. Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals. Clin Genet 1999;55:34-40.
10. Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome. Am J Med Genet 1997;69:299-308.
11. Meara JG, Shah S, Li KK, Cunningham MJ. The odontogenic keratocyst: a 20-year clinicopathologic review. Laryngoscope 1998;108:280-3.
12. Anand VK, Arrowood JP Jr, Krolls SO. Malignant potential of the odontogenic keratocyst. Otolaryngol Head Neck Surg 1994;111:124-9.

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