1. Chandan, Neha
  2. Wang, Stephanie

Article Content


A 64-year-old man presents to the office with a nodular growth on the left nasal ala for several years. The patient noted accelerated growth of the lesion over the past year. His review of systems was unremarkable. The patient states that he has had significant sun exposure in the past. He reports no personal or family history of skin cancer. Physical examination revealed a 4 x 4 cm ulcerated, erythematous nodular plaque with serosanguinous drainage. A punch biopsy was performed, and histopathology revealed findings consistent with a basal cell carcinoma (BCC; Figure 1).

Figure 1 - Click to enlarge in new windowFIGURE 1. A 4 x 4 cm erythematous, nodular plaque on the left nasal ala.

Given the large size of the BCC, what is the most appropriate neoadjuvant treatment for this patient?


A. Topical imiquimod


B. Topical 5-fluorouracil


C. Oral vismodegib


D. Photodynamic light therapy


E. Cryotherapy





C. Oral vismodegib




This patient was diagnosed with a nodular and infiltrative BCC. Key histological features of BCC include basaloid proliferation of cells extending from the epidermis with peripheral palisading. Subtypes include superficial, nodular, and infiltrative BCCs. In superficial BCC, basaloid epithelium rises from the basal layer with tumor nests growing multifocally and confined within the papillary dermis. Nodular BCC is characterized by the tumor-forming solid nodules that can extend beneath the skin, causing tissue destruction and creating an ulcer known as a rodent ulcer (Lear & Smith, 1997). Infiltrative BCC is a potentially aggressive, uncommon subtype of nodular BCC occurring more often in older men and is difficult to treat due to its tendency to penetrate deep into the subcutaneous tissue. This tumor presents histologically as long, thin strands and cords of atypical basaloid epithelium. Our patient's BCC is classified as an advanced or high-risk BCC given its size greater than 2 cm and location in the H zone or high-risk zone on the face (postauricular scalp, ears, preauricular cheek, temples, periorbital, eyelids, nose, lips, chin, and mandible; Dandurand, Petit, Martel, & Guillot, 2006; Lear & Smith, 1997). A combination of surgery, radiotherapy, and targeted therapies, such as Hedgehog (Hh) pathway inhibitors, provides the best prognosis.


Choice of treatment for BCCs is based on factors including type, size, location, and depth of penetration of the tumor (Aditya & Rattan, 2013). Surgical excision is the gold standard treatment for superficial BCCs less than 2 cm on the arms, legs, back, and chest but may not be feasible due to a patient's age or past medical history; radiation therapy may also be an option when a tumor is inoperable due to its size or location (Berking, Hauschild, Kolbl, Mast, & Gutzmer, 2014). Mohs micrographic surgery (MMS) is typically utilized for high-risk lesions and is the preferred treatment modality for BCCs on the face and trunk greater than 2 cm in size with indistinct borders and specific microscopic growth patterns. In a study assessing the 10-year cumulative probabilities of recurrence of facial BCCs, those treated with MMS had a 4.4% recurrence rate compared with those treated with surgical excision (van Loo et al., 2014). Vismodegib, an Hh pathway inhibitor, was given Food and Drug Administration approval in 2012 for the treatment of high-risk BCCs in patients who are not candidates for surgery or radiation therapy. Sonidegib was more recently approved in 2015 for the same indication. The Hh pathway is abnormally activated in patients with BCC, and inhibition of this pathway results in significant clinical responses (Puig & Berrocal, 2015). A new indication for Hh pathway inhibitors is its short-term use as a neoadjuvant therapy before surgical excision. In one study of 11 individuals with at least one BCC greater than 5 mm in diameter who received vismodegib for 4-6 months, neoadjuvant treatment decreased the size of the final surgical lesion by 34.8% (Apalla et al., 2017). In another study of three individuals, use of vismodegib 6 months before Mohs surgery was effective in reducing the size of aggressive BCCs, with two tumors disappearing clinically and one tumor drastically reducing in size after treatment (Alcalay, Tauber, Fenig, & Hodak, 2015). In a study evaluating the overall efficacy of vismodegib on advanced BCCs, 54.5% (18/33) showed an objective response to vismodegib; in addition, 6.0% (2/33) had a complete response, and 48.5% (16/33) had a partial response to this treatment (Fellner, 2012). Upon initiation of vismodegib, careful measurements and tumor dimensions should be recorded at each follow-up visit. No baseline or ongoing laboratory monitoring is required. Adverse effects that should be monitored include possible muscle spasm, alopecia, dysgeusia, dysosmia, diarrhea, and constipation.


Topical imiquimod and topical 5-fluorouracil are both approved by the Food and Drug Administration for the treatment of superficial, low-risk BCCs, with remission rates of 82%-90% and 90%, respectively. Similarly, photodynamic light therapy achieved complete remission in 92% of superficial BCCs in a randomized controlled trial (Berking et al., 2014). Cryotherapy can be effective for the treatment of small and superficial BCCs (Berking et al., 2014).


Our patient was offered radiation therapy, but he declined and opted for vismodegib instead. He was started on vismodegib 150 mg once daily with a significant decrease in the size of the lesion after 2 months of treatment. He will continue taking vismodegib until his planned MMS at a later date.




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