Background

The Nevoid Basal Cell Carcinoma Syndrome is a rare autosomal dominant disorder characterized by multiple basal cell carcinomas, odontogenic keratocysts, tumors, and systemic anomalies.

The diagnosis is made in the presence of two major or one major and two minor criteria.

The major criteria consist of the following:
1) More than 2 BCCs or 1 BCC in patients under the age of 20 years
2) Odontogenic keratocysts of the jaw, histologically proven
3) Three or more palmar or plantar pits
4) Bilamellar calcification of the falx cerebri
5) Bifid, fused or markedly splayed ribs
6) First degree relative with the syndrome

The minor criteria include the following:
1) Macrocephaly
2) Congenital malformations, such as cleft lip or palate, frontal bossing, "coarse facies" and moderate or severe hypertelorism
3) Other skeletal abnormalities, such as Sprengel deformity, marked pectus deformity and marked syndactyly of the digits
4) Radiological abnormalities, such as bridging of the sella turcica, vertebral anomalies, modeling defects of the hands and feet or flame-shaped lucencies of the hands and feet
5) Ovarian fibroma or medulloblastoma.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Gorlin Syndrome
SEX (M:F)	Equal
GEOGRAPHY	Smaller percentage of African-Americans present with skin cancer and have fewer skin cancers than affected Caucasians

 

DISEASE ASSOCIATIONS

CHARACTERIZATION

Nevoid basal cell carcinoma syndrome. Report of a case with associated Hodgkin's disease. Zvulunov A, Strother D, Zirbel G, Rabinowitz LG, Esterly NB. Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226, USA.

J Pediatr Hematol Oncol 1995 Feb;17(1):66-70 Abstract quote PURPOSE: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal-dominant multisystem disorder characterized by various congenital anomalies, multiple cutaneous basal cell carcinomas (BCCs), and increased risk for other benign and malignant tumors. We report a 13-year-old girl with NBCCS who developed cutaneous BCCs 2 years after radiotherapy for Hodgkin's lymphoma. PATIENTS AND METHODS: Review of clinical and laboratory observations of patients with NBCCS suggest a close relationship between radiotherapy and the early emergence of numerous BCCs. However, in vitro studies of the effect of radiosensitivity on cells cultured from patients with NBCCS show inconsistent results. RESULTS: Clarification of the role of radiotherapy in the induction of BCCs in NBCCS requires additional studies. Nevertheless, recognition of the syndrome is important because whenever possible radiotherapy for secondary tumors might be effectively replaced by chemotherapy.

 

PATHOGENESIS	CHARACTERIZATION
Autosomal dominant disorder	Maps to chromosome 9q22.3, 9q31, and 1p32
PTCH Gene mutations	Science 1996;272:1668-71. Cell 1996;85:841-51. Lancet 1992;339:581-2. Nat Genet 1996;14:78-81. Cancer Res 1997;57:2369-72. Human homologue of the Drosophila patched gene, PTCH, is the second tumor suppressor gene (after p53) implicated in the development of BCC PTCH gene has been mapped to chromosome 9q22.3 where a locus for NBCCS had been previously located Sequence analysis of DNA from NBCCS individuals has shown a series of germline mutations in the PTCH gene Subsequently, somatic mutations in the PTCH gene have also been identified in 20% to 30% of the sporadic BCCs studied Mutations detected in the PTCH genes from sporadic BCC also contain UV-specific C to T and CC to TT nucleotide changes Most of the PTCH mutations detected have been nonsense mutations, deletions, and insertions, which lead to altered PTCH proteins.

 

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Radiographs	Odontogenic keratocysts (mandibular retromolarramus area; maxillary second molar area) Computed tomography and radiographs of the skull show a distinctive lamellar calcification of the falx cerebri Intracranial calcification (falx cerebri) Exaggerated mandibular length Macrocephaly Cleft lip and/or palate Large paranasal sinuses Vertebral anomalies (kyphoscoliosis, abnormal segmentation) Rib anomalies (bifid, fused, missing, splayed) Sclerotic bone lesions (rare) Short fourth metacarpal
CT scan and MRI
Laboratory Markers

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General
VARIANTS	Frontal and biparietal bossing Broadened nasal root Low position of the occiput Mild hypertelorism Exotropia Mental retardation (variable) Strabismus
Tumors	Tumors (medulloblastoma, ovarian fibroma)
Acrochordons as a presenting sign of nevoid basal cell carcinoma syndrome Elvira Chiritescu, etal.	J Am Acad Dermatol 2001;44:789-94 Abstract quote Background: Nevoid basal cell carcinoma syndrome (NBCCS) is a genodermatosis with autosomal dominant inheritance. In identified kindreds the diagnosis is relatively easy, but for the patients without family history of this syndrome a high clinical suspicion is necessary for diagnosis. Objective: Acrochordons are distinctly uncommon in childhood. Our purpose was to evaluate skin tags that develop at an early age. Methods: This is a retrospective series evaluation of 7 children who presented with pedunculated papules (acrochordon-like growths). A full history was then correlated with biopsy results in each patient. Results: Clinically, lesions consisted of flesh-colored and pigmented pedunculated papules. Histopathologic examination of these papules showed basal cell carcinomas in each biopsy specimen. Conclusion: We consider that “skin tag”-like basal cell carcinomas in childhood may represent a marker for NBCCS. Early diagnosis of this syndrome and early sun protection of the affected children could help decrease the number of lifetime tumors. Biopsy should be performed on acrochordons in children because they may be the presenting sign of NBCCS. Because these tags may precede other stigmata of the NBCCS, recognition may facilitate early diagnosis and allow early treatment and sun protection.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
General	Basal cell carcinomas have typical morphology
VARIANTS
Cutaneous keratocysts of nevoid basal cell carcinoma syndrome. Barr RJ, Headley JL, Jensen JL, Howell JB.	J Am Acad Dermatol 1986 Apr;14(4):572-6 Abstract quote Four cysts were removed from two unrelated patients with nevoid basal cell carcinoma syndrome. Multiple sections from each cyst were studied. Two cysts showed histologic features similar to keratocysts that occur in the jaws of patients with this syndrome. The cysts were lined by a festooned epithelium consisting of two to five layers of squamous cells that formed keratin without the presence of a granular cell layer. One cyst contained some lanugo hair and a small bud of follicular epithelium. This cyst was therefore similar to cutaneous steatocysts but did not have an identifiable sebaceous component. The second cyst was devoid of hair and adnexal structures and was indistinguishable from a jaw keratocyst. Two other cysts were typical epidermoid (infundibular) cysts. Although speculative, it is likely that some cutaneous cysts in patients with nevoid basal cell carcinoma syndrome are identical to jaw keratocysts and may be another cutaneous marker for this disease complex.
SARCOMATOID CARCINOMA
Primary cutaneous carcinosarcoma arising in a patient with nevoid basal cell carcinoma syndrome. Bhattacharjee P, Leffell D, McNiff JM. Department of Dermatology, Yale University School of Medicine, New Have, CT, USA.	J Cutan Pathol. 2005 Oct;32(9):638-41. Abstract quote   Background: Nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant disorder characterized by developmental abnormalities and neoplasms including basal cell carcinoma (BCC) and sarcomas (i.e. leiomyosarcoma, rhabdomyosarcoma, and fibrosarcoma). Primary cutaneous carcinosarcoma (PCC), a rare tumor composed of malignant epithelial and mesenchymal components, has never been previously described in association with this syndrome. Case report: A 61-year-old Hispanic man with a history of NBCC presented with a 4 cm nodule on the right proximal medial thigh. Pathologic findings: Areas of typical BCC merged with intersecting fascicles of large atypical spindle cells that stained for vimentin and were negative for actin, desmin, CD-34, and S-100 protein. Scattered bizarre solitary cytokeratin-positive epithelioid cells were embedded within the fibrocytic proliferation. Conclusions: Several carcinosarcomas have been reported to contain BCC as the malignant epithelial component, but to our knowledge, this is the first report of PCC associated with NBCC. Mutation in patched tumor suppressor gene on chromosome 9q occurs in BCCs of NBCC, and aberrancies on chromosome 9q are also reported in some carcinosarcomas. It is possible that the known genetic defect on chromosome 9 in this patient contributed to the development of carcinosarcoma.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors
Survival	Patients may die from malignant brain tumors
Odontogenic keratocysts	High recurrence rate (30%-60%) Bilateral, asymmetric, small or large, single or multiple Unilocular or multilocular Mandible > maxilla (3:1)

J Am Acad Dermatol 2000;43:1092-3.
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated October 14, 2005

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