Nevoid Basal Cell Carcinoma Syndrome Workup

Although no routine laboratory studies are helpful for nevoid basal cell carcinoma syndrome (NBCCS), some studies may potentially aid in the diagnosis.

Molecular testing is available to confirm the diagnosis in patients with atypical findings or possibly for prenatal diagnosis. This study may be useful for infants of an affected patient who is too young to have developed diagnostic clinical findings. Because of imperfect sensitivity and specificity, genetic testing should be performed in conjunction with a genetic counselor. Availability and methodology of testing may change with time; this is another reason genetic counseling is recommended. Current and updated information on available genetic testing is available through GeneTests.

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.^{[14, 15]}

Skull radiography

Calcification of the falx cerebri is the most common radiologic finding in NBCCS, occurring in 65-92% of individuals and seen on anteroposterior skull radiographs. This finding is age-related; in one study, calcification of the falx cerebri was observed in 37% of patients younger than 20 years and in 77-79% of patients older than 20 years. However, this finding may also be seen in approximately 5% of unaffected individuals.

Calcification of the tentorium cerebelli is observed in 20-40% of patients with NBCCS. This is more typically seen on lateral skull radiographs. Calcification of the petroclinoid ligament, pia, and choroid plexus may also be observed. Calcification of the diaphragma sellae may be observed in 60-80% of patients with NBCCS, as compared with 4% of the healthy population; however, some studies have suggested both a lower prevalence in the persons affected and a higher prevalence in unaffected relatives, making this finding less specific.

Therefore, consider anteroposterior and lateral radiographs of the skull or MRI if indicated to aid in diagnosis.

Skeletal radiography

Bifid, hypoplastic, fused, partially missing, or splayed ribs are observed in 38-60% of patients with NBCCS. These features may be helpful diagnostic criteria, because they are present in children before other features may show up and because they are uncommon in the general population. The most commonly affected ribs are the third, fourth and fifth ribs, although others may be involved. It is important that the radiologist specifically look for these features.

Malformations at the occipitovertebral junction and cervical or upper thoracic vertebral fusion may also be observed. In one study, calcification of the nuchal ligament occurred in 18% of affected people. Small, pseudocystic, lytic bone lesions known as "flame-shaped lucencies" are found on radiographs of the hands (30%) and feet (17%) of affected people.

Therefore, consider chest, cervical and thoracic spine (anteroposterior and lateral), and hand or foot radiographs if indicated to aid in the diagnosis. It is important to ask the radiologist to specifically look for findings of NBCCS because he or she may not otherwise comment on these.

Dental panoramic radiography

This screening is useful for the finding of odontogenic keratocysts, which are relatively common in NBCCS. When monitoring a child with NBCCS, consider regular dental visits plus panoramic radiography to detect these cysts.

Cardiac fibromas have an incidence as high as 3% in some studies (rarer in other studies). In patients with NBCCS, one might consider a baseline echocardiogram at birth or within the first year of life and then subsequently, primarily if clinical suspicion arises for a cardiac fibroma.

Magnetic resonance imaging (MRI) may be more sensitive than plain radiography for calcification, and it may be indicated if medulloblastoma is suspected in a child with NBCCS. Because of the concern about exposure to radiation in patients with the syndrome, MRI is the preferred imaging modality over computed tomography (CT) scanning. Consider an annual MRI up to age 7 years, to coincide with the main age of risk of medulloblastoma.

To diagnose ovarian fibromas, consider performing pelvic ultrasonography around puberty, as a baseline, and later in life if symptoms are present.

Because the histologic features of the individual skin cancers are indistinguishable from ordinary BCC and include the full spectrum of histologic subtypes, biopsy of the skin lesions is recommended. Biopsy of jaw cysts are also recommended, as odontogenic keratocysts have a characteristic pathologic finding that shows the lining with keratinizing epithelium.