Intraoperative Dermoscopy for Identification of Early Basal Cell Carcinomas in Basal Cell Nevus Syndrome Disclosures

• I have no industry related, financial, or other disclosures Goals

• Discuss the clinical characteristics of Nevoid Basal Cell Carcinoma Syndrome

• Identify the dermascopic features of basal cells found in syndromic patients

• Discuss a highly effective and well tolerated treatment modality ▫ The CO2 Laser Gorlin’s Syndrome • Nevoid Basal Cell Carcinoma Syndrome (NBCCS) ▫ Rare autosomal dominant mutation of PTCH gene on C-some 9q ▫ Prevalence is approximately 1/100,000

• Main Cutaneous Characteristics ▫ Multiple Basal Cell Carcinomas (BCCs) ▫ Palmar and plantar pits Diagnostic Criteria (2 Major, 1 Minor)

• Major Criteria ▫ Cutaneous  Over 5 BCCs in a lifetime or one before age 30  Palmar and plantar pits ▫ Radiographic  Lamellar calcification of the falx cerebri  Jaw keratocysts or polyostotic bone cyst ▫ Historical  First degree relative with NBCCS ▫ Controversial  Medulloblastoma

Diagnostic Criteria • Minor Criteria ▫ Macrocephaly ▫ Cleft lip and/or palate ▫ Vertebral and/or rib abnormalities ▫ Polydactyly ▫ Ovarian and/or cardiac fibromas ▫ Ocular abnormalities Variable Expressivity 105 people aged 4 months to 87 years • BCC in 80 % Whites and 38% African Americans • Palmar pits in 80% • Jaw cysts in 74% • Facial dysmorphism in 55% • Radiographic changes in up to 65% ▫ Falx cerebri calcification ▫ Bifid ribs ▫ Hemi- or fused vertebrae ▫ Flame shaped lucencies of the phalanges, metacarpal, and carpal bones 100%

90%

80%

70%

60%

50%

40%

30%

20%

10%

0% BCC Palmar Pits Jaw Cysts Facial Dysmorphism Clinical Challenges for Dermatologists • Basal Cell Carcinomas (BCCs) ▫ Multiple ▫ Early ▫ Can be difficult to identify • Treatment ▫ Safe ▫ Effective ▫ Well tolerated ▫ Efficient ▫ Cosmetically acceptable Dermatoscopic findings in BCC

• Gross Clinical BCC Types ▫ Nevoid  Pigmented  Additional subtypes ▫ Acrochordon-like ▫ -like ▫ Featureless (very small BCCs) ▫ Typical BCC (more common with increasing age) Nevoid BCC

• Always present ▫ Pigment without a defined network • May be present ▫ Brown-grey dots and globules ▫ (usually over 3mm) ▫ Leaf-like areas (larger lesions) ▫ Smooth and pearly surface

Featureless BCCs

• Very small • Round • colored • May be polypoid 1

Case Presentation • 1-year-old boy ▫ Father with history of NBCCS • Findings ▫ Macrocephaly with frontal bossing ▫ Multiple fused vertebrae • By age 3 ▫ Palmar pit on the left palm ▫ Several skin-colored papules with brown globules noted via dermoscopy on his occipital scalp and left eyelid • Over the next several years, he developed over 100 BCCs

Treatment

• Treatment goals for our patient ▫ Safe ▫ Effective ▫ Well tolerated ▫ Efficient ▫ Cosmetically acceptable Treatment Options for BCC in Gorlin’s Syndrome • Surgical ▫ CO2 Laser ▫ ▫ Excision ▫ Mohs • Topical ▫ Imiquimod ▫ 5-FU ▫ PDT • Targeted ▫ Vismodegib CO2 laser • Study by Nouri, et al. ▫ Patient with phototype IV and BCNS ▫ 100 BCCs on a patient’s trunk, 20 on the neck, and 2 on the face (all 1-4mm in size) identified

▫ Treated with CO2 laser  Endpoint = skin yellowing  500 mJ, 5 W, 3 mm spot size, three to four passes

▫ 1 month later 6 random sites chosen for post-op Mohs sections  No remaining malignancy identified CO2 Laser

• Advantages ▫ Precision treatment and decreased postop pain ▫ Low recurrence (<3% of lesions smaller than 10mm) ▫ Rapid tx of many lesions with short healing time (about 2 wks) ▫ Better cosmesis (minimal and scarring) CO2 Laser

• When is it not appropriate… ▫ BCCs larger than 10mm ▫ Ulcerative, ill-defined, or very thick BCCs Intraoperative Dermoscopy Followed by CO2 Laser Ablation • Phoenix Children’s Hospital ▫ Harper Price, MD and Ronald Hanson, MD et al.

▫ Patient is seen in clinic for skin check  BCCs identified by dermoscopy without  Exceptions ▫ Diagnostic uncertainty ▫ Larger than a few millimeters

▫ Patient is scheduled for CO2 laser surgery

Intraoperative

• Patient arrives at facility and undergoes induction with general anesthesia • Dermoscopy again used intraoperatively to identify BCCs

Treatment

• CO2 laser ▫ 10,600nm, 3-5 W in a continuous fashion

▫ Each is treated with one to four focal passes

▫ Destruction noted by the endpoint of dermal tightening and slight crust formation

Post-treatment

• Usually complete recovery is in 1-2 weeks

• Slight hypopigmentation with little if any scarring

• Recurrence does occur occasionally

Patient Satisfaction

• Cosmetic results preferred over punch excision

• Appreciate the ability to treat multiple sites in a single session

• Report minimal discomfort Conclusions • Basal Cell Nevus Syndrome is a disease with both diagnostic and therapeutic challenges • Cutaneous Clues ▫ Early BCCs ▫ Palmar pits ▫ Facial dysmorphism • CO2 laser ▫ Effective ▫ Efficient ▫ Safe ▫ Well tolerated ▫ Cosmetically acceptable References

• Feito-Rodriguez, M., et al "Dermatoscopic characteristics of acrochordon-like basal cell carcinomas in Gorlin- Goltz syndrome." Journal of the American Academy of . 60. (2009): 857-861. Print. • Jarrett, R., et al "The Dermoscopy of Gorlin Syndrome: Pursuit of the Pits Revisited." Archives of Dermatology. 146.5 (2010): 582. Print. • Kimonis VE., et al. “Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome.” American Journal of Medical Genetics. 1997 Mar, 69 (3): 299-308. • Kiwilsza, M., et al. "Gorlin-Goltz syndrome – a medical condition requiring a multidisciplinary approach." Med Sci Monit. 18.9 (2012): 145-153. Print. • Kolm, I., et al "Dermoscopy in Gorlin-Goltz Syndrome." Dermatologic Surgery. 32. (2006): 847-851. Print. • Lam, C., et al. "PTCH-ing It Together: A Basal Cell Nevus Syndrome Review." Dermatologic Surgery. 39. (2013): 1557-1572. Print. • Lien, M., et al. "Nonsurgical Treatment Options for Basal Cell Carcinoma." Journal of . (2011): 1-5. Print. • Nouri, K., et al "Ultrapulse CO2 Used for the Successful Treatment of Basal Cell Carcinomas Found in Patients with Basal Cell Nevus Syndrome." Dermatologic Surgery. 28. (2002): 287-290. Print. • Tang, J., et al. "Inhibiting the Hedgehog Pathway in Patients with Basal-Cell Nevus Syndrome." New England Journal of Medicine. 366. (2012): 2180-2188. Print. • Tiberio, R., et al. "Pigmented basal cell carcinomas in Gorlin syndrome: two cases with different dermatoscopic patterns." Clinical and Experimental Dermatology. 36. (2011): 617-620. Print. • Wolfe, C., et al. "A possible chemopreventive role for photodynamic therapy in Gorlin syndrome: a report of basal cell carcinoma reduction and review of literature." Australasian Journal of Dermatology. 54. (2013): 64-68. Print. • Wolfe, C., et al "Basal Cell Carcinoma Rebound After Cessation of Vismodegib." Dermatologic Surgery. 38. (2012): 1863-1866. Print.