Mandible & maxilla
Odontogenic cysts
Nevoid basal cell carcinoma syndrome
Last author update: 1 February 2014
Last staff update: 21 December 2020
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PubMed Search: Nevoid basal cell carcinoma syndrome [title]
Table of Contents
Definition / general | Terminology | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Diagrams / tables | Laboratory | Radiology description | Radiology images | Echocardiogram | Pelvic ultrasound | Prognostic factors | Case reports | Treatment | Clinical images | Differential diagnosis | Additional referencesCite this page: Morrison A. Nevoid basal cell carcinoma syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/mandiblemaxillabasalcellnevus.html. Accessed February 6th, 2023.
Definition / general
- Inherited multisystem disorder due to germline mutations in the human homolog of the patched (PTCH) gene that predisposes to overgrowth, tumor formation and skeletal abnormalities
Terminology
- Basal cell nevus syndrome (BCNS)
- Gorlin syndrome
- Gorlin-Goltz syndrome
- Nevoid Basal Cell Carcinoma Syndrome (NBCCS)
- Basal cell carcinoma nevus syndrome (BCCNS)
- Fifth phakomatosis
- Bifid-rib basal-cell nevus syndrome
Epidemiology
- Prevalence estimated at 1 in 57,000
- 30 - 40% of cases represent a de novo mutation
Pathophysiology
- Genetic basis lies in causative mutations in several genes in the sonic hedgehog signaling pathway (see Etiology and Diagrams / tables)
- Sporadic cases thought to follow Knudson model such that two somatic "hits" in same cell are required for sporadic cases of NBCS
- One somatic "hit" plus the inheritance of one defective allele underlies familial cases
- Loss of function mutations in PTCH1, a tumor suppressor gene, result in premature termination of the PTCH protein which impacts multiple organ systems
Etiology
- Autosomal dominant
- High penetrance and variable expressivity
- Most commonly caused by mutations in the PTCH1 gene on chromosome 9q22
- Less commonly PTCH2 gene on 1p32, or the SUFU gene on 10q24-q25
Clinical features
- Great deal of variability in presentation may contribute to delayed diagnosis
- Prominent features may include:
- Head / neck / face / jaw: odontogenic keratocysts
- Neurologic: medulloblastoma
- Genitourinary: ovarian fibromas
- Cutaneous: basal cell carcinomas (BCC), palmar or plantar pitting
- Skeletal: rib anomalies, polydactyly of the hands or the feet, hallux valgus, pectus excavatum or pectus carinatum, syndactyly of the second and third fingers
- Cardiovascular: cardiac fibroma
- Opthalmologic: strabismus, hypertelorism, congenital cataracts
Diagnosis
- Major and Minor Criteria: (eMedicine: Nevoid Basal Cell Carcinoma Syndrome Clinical Presentation [Accessed 8 June 2018])
- No studies define sensitivity and specificity of which phenotypic combination is most accurate for diagnosis
- Recent discussion to move medulloblastoma (also known as primitive neuroectodermal tumor) to major, and not a minor, criterion as this may lead to increased early detection if recognized as a potential indicator of an underlying syndrome, since it typically manifests in children 2 years of age and younger
- Criteria for evaluation, "triggers" for screening:
- Odontogenic keratocysts in children < 20 years of age
- BCC in persons < 20 years of age
- Palmar or plantar pits
- Lamellar calcification of the falx cerebri
- Medullobastoma with desmoplastic histology in combination with any of the other major or minor criteria
- See Laboratory for Genetic Testing
Diagrams / tables
Images hosted on other servers:
Sonic Hedgehog pathway
Diagnostic protocols
Prevalence and frequency of
major criteria in 4 studies
Laboratory
- Genetic Testing:
- The positive mutation detection rate of sequence analysis for PTCH1 is approximately 75% in patients meeting clinical criteria, but has been reported as low as 60%
- Although genetic testing is considered the gold standard for diagnosis, it is also very expensive and can be cost prohibitive
- Clinical criteria are quite good in establishing a suspected diagnosis and that molecular-genetic confirmation is not warranted in all cases
- Genetic testing for PTCH1, the most common mutation, is warranted in these clinical scenarios, as the results may impact diagnosis and management within an individual or a family:
- Prenatal testing if known familial mutation
- Confirmatory diagnosis in patients with some clinical signs but not meeting criteria to allow for increased surveillance and improved patient care outcomes
- Predictive testing for patients with an affected family member who is at risk but does not meet clinical criteria
Radiology description
- MRI / CT: paramount concern in patients with syndrome is exposure to radiation; therefore, imaging should be selected carefully:
- Bilateral hyperplasia of coronoid process of mandible, odontogenic keratocysts, mandibular prognathism
- Calcification of falx cerebri, medulloblastoma
- Fused vertebrae, kyphosis, lumbarized sacrum, scoliosis
- Marfanoid habitus
- Polydactyly, short metacarpals, flame shaped radiolucencies of the hands and feet
- Spontaneous fractures
Radiology images
Images hosted on other servers:
Multiple odontogenic cysts
Odontogenic keratocysts
Multiple KCOTs
Multiple unilocular radiolucencies
Radiolucent area with minimum cortical plate expansion
Hypodense areas
Well defined round cystic mass
Echocardiogram
- 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
Pelvic ultrasound
- At puberty as a baseline, and later in life if symptoms are present, for the diagnosis of ovarian fibroma
Prognostic factors
- Morbidity and premature mortality primarily related to the syndrome related development of skin cancers and other tumors
- Actual mortality rates are unavailable
- Morbidity from multiple skin cancers and their treatment may be severe
Case reports
- Oral cavity / gnathic:
- 19 year old man with undifferentiated sinonasal carcinoma (Int J Surg Pathol 2007;15:303)
- 24 year old man with oral diffuse B cell non-Hodgkin lymphoma (Indian J Pathol Microbiol 2011;54:388)
- 38 year old man with associated unicystic ameloblastoma associated with the novel K729M PTCH1 mutation (Cancer Genet 2012;205:177)
- 39 year old man presenting with myolipoma of tongue base (J Laryngol Otol 2008;122:1130)
- 44 year old patient with concurrent adenoid cystic carcinoma of salivary gland (J Am Acad Dermatol 2003;48:S64)
- 55 year old man with resolution of odontogenic keratocysts of the jaw in basal cell nevus syndrome with GDC-0449 (Arch Dermatol 2011;147:839)
- Bilateral hyperplasia of mandibular coronoid processes (Am J Med Genet 2002;110:400)
- Basal cell carcinoma of the buccal mucosa (Int J Surg Pathol 2011;19:348)
- Tonsillar inclusion cysts (Ear Nose Throat J 2006;85:818)
- Skin:
- 6 month old infant with congenital linear unilateral basal cell nevus (J Cutan Pathol 2007;34:65)
- 19 year old man with apocrine poroma (Am J Dermatopathol 1999;21:31)
- 23 year old woman with linear unilateral basal cell nevus (Cutis 2006;78:122)
- 63 year old woman with chronic hip pain and diffuse skin lesions throughout her body (Arch Pathol Lab Med 2004;128:819)
- 72 year old man with multiple skin cysts in nevoid basal cell carcinoma syndrome (Dermatology 2008;216:159)
- Cutaneous keratocysts (Int J Surg Pathol 2003;11:36)
- Eosinophilic pustular folliculitis (Acta Derm Venereol 2001;81:202)
- Associated with a palmar epidermoid cyst, milia and maxillary cysts (Br J Dermatol 2001;145:508)
- BerEP4 negative basal cell carcinoma on palm (J Dtsch Dermatol Ges 2011;9:140)
- Patched mutations and hairy skin patches (Am J Med Genet A 2006;140:2625)
- Unusual cystic scalp lesions (Pediatr Dermatol 2010;27:204)
- Gastrointestinal:
- 52 year old man with associated small bowel carcinoma and mesenchymal proliferation of GI tract (BMC Cancer 2010;10:360)
- With concomitant ulcerative colitis and rectal cancer (Inflamm Bowel Dis 2009;15:488)
- Skeletal
- Hypoplastic thumb in Gorlin syndrome (J Plast Reconstr Aesthet Surg 2007;60:440)
- Neuro / Ocular
- 11 year old girl with spontaneous recovery from medulloblastoma (Pediatr Neurol 2003;28:231)
- 13 year old girl with conjunctival ganglioglioma as a feature of basal cell nevus syndrome (J AAPOS 2011;15:387)
- 13 to 19 year old patients with empty sella syndrome (Brain Dev 2000;22:272)
- 20 year old woman with meningeal calcification (BMJ Case Rep 2013;2013)
- 24 year old man with combined hamartoma of retina and retinal pigment epithelium in Gorlin syndrome (Arch Ophthalmol 2000;118:1004)
- 34 year old man with bilateral epiretinal membranes in Gorlin syndrome associated with a novel PTCH mutation (Am J Ophthalmol 2007;143:346)
- Intracranial calcifications in childhood medulloblastoma (AJNR Am J Neuroradiol 2000;21:790)
- Chest:
- Mediastinal fetal rhabdomyoma (Virchows Arch 2011;459:235)
- Presenting as prenatal chylothorax in a girl (Prenat Diagn 2005;25:997)
- Other:
- 11 year old boy with testicular thecoma and nevoid basal cell carcinoma syndrome (J Pediatr Surg 2010;45:E1)
- Atlanto-occipital ligament calcification: a novel sign in nevoid basal cell carcinoma syndrome (Anticancer Res 2010;30:4265)
- Two unusual cases of recurrent, bilateral, multinodular, calcified ovarian fibromas with conservative surgical treatment (J Minim Invasive Gynecol 2012;19:248)
- Bilateral adrenal cystic lymphangiomas in nevoid basal cell carcinoma (Gorlin-Goltz) syndrome (J Comput Assist Tomogr 1999;23:562)
Treatment
- Requires multidisciplinary approach including evaluations by specialists to assess and manage abnormalities as they develop: possible / probable consultations with dermatology, genetics, pediatrics, neurology, cardiology, gynecology, oral and maxillofacial surgeon
- Involves surveillance for and treatment of associated findings
- Most of findings involve tumors (benign and malignant), so treatment is often surgical, but in some cases, pharmaceutical agents (see N Engl J Med 2012;366:2180) may be available for certain manifestations
Clinical images
Images hosted on other servers:
Facial features:
Increased inner canthal distance
Hyper pigmented plaques
Clinical features of NBCCS
Palmar pits:
Multiple pits on the palm
Palmer pits in the hypothenar eminence
Small brown papules and palmar pits
Basal cell carcinoma:
Nodular pigmented lesion
Differential diagnosis
- Multiple basal cell carciomas are listed as a prominent feature in these syndromes: Gorlin, Bazex-Dupré-Christol, Rombo, xeroderma pigmentosum
- Basal cell carcinoma may represent a relatively common, although less specific finding in these genodermatoses and medical conditions:
- Arsenic exposure, Bloom, Brooke-Spiegler, cartilage-hair hypoplasia, Cowden, epidermodysplasia verruciformis, melanin biosynthesis disorders (oculocutaneous albinism and Hermansky-Pudlak syndrome), Muir-Torre syndromes, Rothmund-Thomson, Schöpf-Schulz-Passarge, Werner
