Nevoid Basal Cell Carcinoma Syndrome Clinical Presentation

Updated: Mar 29, 2017
  • Author: Daniel Berg, MD; Chief Editor: Dirk M Elston, MD  more...
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Presentation

History

Many of the features of nevoid basal cell carcinoma syndrome (NBCCS) present as signs rather than symptoms. The presence of symptoms is most likely related to the major findings. For example, local invasion of an aggressive BCC may lead to pain or symptoms (eg, neurologic) related to local invasion. Metastasis is extremely rare.

Head/face symptoms

Odontogenic keratocysts (also called keratocystic odontogenic tumors) may be asymptomatic, or they may manifest as jaw pain or abnormal dentition.

Neurologic symptoms

Medulloblastoma, a cerebellar tumor of young childhood, may manifest as neurologic symptoms in an affected child.

Genitourinary symptoms

Ovarian fibromas are usually asymptomatic, but they may present as pain secondary to torsion.

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Physical Examination

Several studies have documented the incidence of the various features found in nevoid basal cell carcinoma syndrome (NBCCS). [11, 12, 13, 14, 15] The syndrome is present (inherited) at birth and most commonly manifests itself with either BCCs (usually multiple) occurring at a young age (third decade or earlier) or odontogenic keratocysts presenting in the second or third decade.

Other incidental findings, such as cleft lip, or asymptomatic findings, such as hypertelorism, may be noticed earlier, but these features may not lead to the diagnosis until the development of more specific findings. Findings usually seen in the syndrome, such as jaw cysts, BCCs, calcification of the falx, and ovarian fibromas, develop more commonly with increasing age in the individual who is affected. Some findings are present earlier in childhood—for example, palmar/plantar pits; craniofacial features like macrocephaly, frontal bossing, and palate abnormalities; and radiologic findings that are distinct from adults with NBCCS (see Radiography). [16]

Medulloblastoma, though a relatively less common manifestation of NBCCS, is a tumor of early childhood. Radiologic abnormalities, such as bifid ribs, or asymptomatic findings, such as palmar pits, may be present at a higher frequency in childhood; these findings may be helpful in making an early diagnosis. [17]

Head and face

Characteristic facies may occur due to increased calvarial size. Other contributing features include increased head circumference; a broadened nasal root; frontal and biparietal bossing, mild hypertelorism; and an exaggerated length of the mandible. Cleft lip or palate may occur in 3-5% of patients.

Odontogenic keratocysts are seen in 74-80% of patients. These lesions usually begin to develop in the first decade (after age 7 y), with the peak incidence in the second and third decades, which is younger than that which is seen with isolated odontogenic cysts. Odontogenic keratocysts are more common in the mandible than in the maxilla. Although these lesions are usually asymptomatic, they may cause pathologic fracture, swelling, loose teeth, or displacement of developing permanent teeth. Jaw cysts appear to occur only rarely after age 30 years.

Ophthalmologic findings

Ocular findings include congenital blindness due to corneal opacity and cataract or glaucoma, occurring in as many as 10-15% of patients. Up to 40% of patients may have milialike lesions on the palpebral conjunctiva. Strabismus (exotropia) may be seen, as may other rare ocular findings. [1]

Cutaneous and connective tissue findings

BCCs are the most common finding in NBCCS. In a study of white persons older than 40 years, 97% had BCCs. The tumors are usually multiple, and they are most common on the face, neck, and upper part of the trunk—that is, in sun-exposed areas—but they are also increased in relatively sun-protected areas. As is true for sporadic BCCs, some lesions may become aggressive, although many are not. (See the images below.)

Multiple basal cell carcinomas on the back of a pa Multiple basal cell carcinomas on the back of a patient with nevoid basal cell carcinoma syndrome.
Multiple small papules on the neck and upper trunk Multiple small papules on the neck and upper trunk in a 10-year-old patient. Biopsy confirmed basal cell carcinoma.

The tumors largely begin to appear between puberty and age 35 years, but they may appear at a younger age. Kimonis et al found that 50% of white individuals had their first BCC by age 21.5 years and 90% had it by age 35 years. [15] Lesions may present as any kind of clinical or histologic BCC; however, some lesions may be small and resemble milia, small nevi, tags, or hemangiomas. Milia may be seen in as many as 30% of patients with NBCCS.

Asymmetric palmar and/or plantar pits are seen in 65-87% of all people with NBCCS (see the following image). When these lesions do develop, they often do so early in life, being found in as many as 80% of patients younger than 10 years. Thus, palmar and/or plantar pits may be a helpful early criterion for the diagnosis of NBCCS. More than 3 pits should be noted, because the relevance of 1 or 2 pits may not be diagnostic.

Palmar pits in an adult. Palmar pits in an adult.

Other tumors, including fibrosarcoma, rhabdomyosarcoma, may also be increased in frequency in persons with NBCCS.

Neurologic findings

Medulloblastoma (malignant tumors of the cerebellum) occurs in 1-4% of patients. These tumors present in early childhood, with the greatest risk from birth to age 3 years, although cases have been reported as late as 7 years. Meningiomas may also be increased in frequency in persons with NBCCS.

Genitourinary findings

Genitourinary findings include bilateral calcified ovarian fibromas, which are found in 14-24% of women; these are often asymptomatic and rarely become malignant. Men may have associated cryptorchidism or gynecomastia and reduced body hair.

Skeletal findings

Skeletal abnormalities include polydactyly of the hands or the feet, hallux valgus, pectus excavatum or pectus carinatum, and syndactyly of the second and third fingers (see the image below).

Syndactyly is noted in some affected persons such Syndactyly is noted in some affected persons such as this 8-year-old boy.

Kyphoscoliosis may also be more common or more severe in NBCCS. Sprengel deformity of the shoulder occurs in 5-10% of patients. A short fourth metacarpal may be seen with increased frequency, although as many as 10% of healthy persons also have this sign.

Cardiovascular findings

Cardiac findings are less common, but an increased risk of cardiac fibroma may be present in approximately 2% of cases, although none was found in the large study by Kimonis et al. [15] These may be asymptomatic or cause arrhythmia or cardiac flow obstruction. Cardiac fibroma, if present, usually develops in children.

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Major and Minor Criteria

Despite the understanding of the underlying genetic basis of nevoid basal cell carcinoma syndrome (NBCCS), the diagnosis remains clinical. Although not absolute, the following diagnostic criteria were suggested by Kimonis et al to help guide the clinician in choosing laboratory evaluation for both diagnostic purposes and ongoing surveillance. [15] Clinicians must remember that some of the findings listed may present at different ages; therefore, ongoing surveillance with respect to diagnosis may be needed. The diagnosis of NBCCS is made in the presence of 2 major criteria or 1 major and 2 minor criteria.

Major criteria are as follows:

  • Major criteria include the following:

  • More than 2 BCCs or 1 BCC in patients younger than 20 years

  • Odontogenic keratocysts of the jaw (proven by histologic analysis)

  • Three or more palmar or plantar pits

  • Bilamellar calcification of the falx cerebri

  • Bifid, fused, or markedly splayed ribs

  • First-degree relative with NBCCS

Minor criteria are as follows:

  • Macrocephaly

  • Congenital malformations, such as cleft lip or palate, frontal bossing, coarse facies, and moderate or severe hypertelorism

  • Other skeletal abnormalities, such as Sprengel deformity, marked pectus deformity, and marked syndactyly of the digits

  • Radiologic abnormalities such as bridging of the sella turcica, vertebral anomalies such as hemivertebrae, fusion or elongation of the vertebral bodies, modeling defects of the hands and feet, or flame-shaped lucencies of the hands and the feet

  • Ovarian fibroma or medulloblastoma

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