Gorlin-Goltz syndrome presenting with multiple basal cell carcinomas and odontogenic keratocysts: a case report

INTRODUCTION

Gorlin-Goltz syndrome, also known as NBCCS, is a rare multisystem genetic disorder characterized by developmental abnormalities and predisposition to neoplasms.¹ It was first described by Jarisch and White in 1894 and later delineated by Gorlin et al.²

The syndrome follows an autosomal dominant inheritance pattern with high penetrance and variable expressivity. It is caused by mutations in the PTCH1 gene located on chromosome 9q22.3-q31, resulting in abnormal activation of the Sonic Hedgehog signaling pathway.³

The prevalence ranges from 1 in 57,000 to 1 in 256,000 individuals with no gender predilection.⁴ Clinical manifestations typically appear during adolescence but may present later in life.

Major diagnostic criteria include multiple basal cell carcinomas, odontogenic keratocysts, palmar or plantar pits, calcification of the falx cerebri, and bifid ribs.⁵ Early diagnosis is essential for surveillance and prevention of complications such as aggressive basal cell carcinomas and medulloblastoma.⁶

CASE REPORT

A 45-year-old male presented with multiple lesions over the face for the past 10 years. The lesions were initially small and gradually increased in size, ranging from 2×2 cm to 5×5 cm. Some lesions showed rolled borders with central ulceration.

On dermatological examination, multiple well-defined plaques with pearly margins and central indentation were observed over the face, clinically suggestive of basal cell carcinoma. Bilateral palmar pits (>3 in number) were noted.

The patient also complained of jaw swelling associated with pain, pus discharge, loosening of teeth, and trismus. There was no significant family history.

Systemic examination including cardiovascular, respiratory, and genitourinary systems revealed no abnormalities.

Radiological findings

Cone beam computed tomography (CBCT) revealed multiple well-defined radiolucent lesions involving the right maxillary region, mandibular ramus, and symphyseal region. These findings were consistent with odontogenic keratocysts.

Chest imaging demonstrated bifid ribs, while CT scan of the skull showed bilamellar calcification of the falx cerebri.

Histopathological findings

Histopathological examination of the facial lesion revealed nests and islands of basaloid cells arising from the epidermis and extending into the dermis. Peripheral palisading, stromal retraction spaces, and increased mitotic activity were noted, consistent with basal cell carcinoma.

The histopathology report from Dr. R. Ahmed Dental College confirmed features of odontogenic keratocyst. Sections showed odontogenic cystic lining supported by connective tissue stroma, with stratified epithelium exhibiting surface keratinization and palisaded basal cells. The underlying stroma was fibrocollagenous with scant inflammatory infiltrate.

Based on the presence of multiple basal cell carcinomas, odontogenic keratocysts, palmar pits, bifid ribs, and falx cerebri calcification, the diagnosis of Gorlin-Goltz syndrome was established.⁷

Treatment and follow-up

The patient was managed with a multidisciplinary approach involving dermatology and maxillofacial surgery teams.

Cutaneous lesions were treated using a combination of: Topical imiquimod 5% cream, surgical excision of larger lesions, cryotherapy for selected lesions.

Odontogenic keratocysts were managed by surgical enucleation and curettage.

The patient was advised strict photoprotection, including avoidance of ultraviolet exposure and regular use of sunscreen.

At 6-month follow-up, there was significant clinical improvement with no evidence of recurrence of cutaneous lesions or progression of jaw lesions. The patient remains under regular surveillance. Genetic counselling was advised.

DISCUSSION

Gorlin-Goltz syndrome is a rare multisystem disorder with variable clinical presentation. Diagnosis is based on established criteria requiring either two major criteria or one major and two minor criteria.⁸

In the present case, multiple major criteria including basal cell carcinomas, odontogenic keratocysts, palmar pits, bifid ribs, and falx cerebri calcification were present, confirming the diagnosis.

Basal cell carcinomas in NBCCS often present at an earlier age and tend to be multiple.⁹ They may mimic benign lesions such as nevi or seborrheic keratosis, leading to delayed diagnosis.

Odontogenic keratocysts are among the earliest manifestations and may present with jaw swelling, pain, and dental abnormalities.¹⁰ CBCT plays a crucial role in identifying these lesions and assessing their extent.

The absence of family history in this patient suggests a possible de novo mutation, which has been reported in a significant number of cases.¹¹

Management of NBCCS requires a multidisciplinary approach. Treatment options for basal cell carcinoma include surgical excision, topical therapy, cryotherapy, and photodynamic therapy.¹²

Recent advances include Hedgehog pathway inhibitors such as vismodegib and sonedegib, which are effective in advanced or inoperable cases.¹³

Regular follow-up is essential for early detection of complications such as medulloblastoma, particularly in younger patients.¹⁴

CONCLUSION

Gorlin–Goltz syndrome is a rare genetic disorder with significant clinical implications due to its multisystem involvement and oncogenic potential. This case highlights the importance of early recognition of characteristic clinical and radiological features. A multidisciplinary approach and long-term follow-up are essential for optimal management. Early diagnosis and appropriate intervention can significantly reduce morbidity and improve patient outcomes.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

REFERENCES

1. 1. Lo Muzio L. Nevoid basal cell carcinoma syndrome. Orphanet J Rare Dis. 2008;3:32.
2. 2. Gorlin RJ, Goltz RW. Multiple nevoid basal-cell epithelioma. N Engl J Med. 1960;262:908-12.
3. 3. Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, et al. Mutations of the patched gene. Cell. 1996;85(6):841-51.
4. 4. Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA. NBCCS complications. J Med Genet. 1993;30(6):460-4.
5. 5. Kimonis VE, Goldstein AM, Pastakia B, Yang ML, Kase R, DiGiovanna JJ, et al. Clinical manifestations. Am J Med Genet. 1997;69(3):299-308.
6. 6. Bree AF, Shah MR, BCNS Colloquium Group. Consensus statement from the first international colloquium on basal cell nevus syndrome (BCNS). Am J Med Genet A. 2011;155A(9):2091-7.
7. 7. Manfredi M. Odontogenic keratocysts. Oral Surg Oral Med Oral Pathol. 2004;98:698-703.
8. 8. Evans DG. Diagnostic criteria review. J Med Genet. 2004;41:421-8.
9. 9. Shanley S. BCC in NBCCS. J Med Genet. 1994;31:754-8.
10. 10. Parikh NR. Nonsyndromic multiple odontogenic keratocysts. Adv Dent Res. 2010;1:71-4.
11. 11. Pastorino L. Molecular diagnosis. Clin Genet. 2009;75:109-16.
12. 12. Arits AH. Treatment of BCC. Br J Dermatol. 2013;169:789-99.
13. 13. Sekulic A. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med. 2012;366(23):2171-9.
14. 14. 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(3):299-308.