Case Letter

Nonmalignant Cutaneous Findings Associated With Vemurafenib

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Practice Points

  • Prior to starting a BRAF inhibitor, clinicians should perform a baseline total-body skin examination and follow-up every 2 months.
  • Take photographs of the patient's entire body on initial total-body skin examination.
  • Encourage sun protection for exposed areas on the body in all seasons.



To the Editor:

A 53-year-old woman was referred by her oncologist to our dermatology office with lesions on the face and body that presented 8 days after starting vemurafenib 960 mg twice daily for metastatic melanoma. The patient denied any symptoms from the lesions but was concerned they would spread to cover her entire face and body.

The patient's medical history included a diagnosis of metastatic melanoma 6 years prior to presentation. She stated that the primary cutaneous melanoma site was unknown. The patient had endured numerous surgeries to excise lymph node tumors, with some lesions up to 3 cm. The patient recently started vemurafenib, a treatment for BRAF V600E mutation-positive metastatic melanoma. The patient's personal history was notable for hepatitis A, B, and C, and her family history revealed her mother had metastatic lung cancer.

Physical examination revealed numerous 2- to 3-mm, round-oval, flesh-colored to light-brown papules on the cheeks, chest, abdomen (Figure 1), back, and both arms and legs. Some papules were inflamed and some had a stuck-on appearance. Lesions on the chest between the breasts and inframammary region were slightly inflamed. Two skin biopsies were performed. Biopsy of the lesion on the right lateral back revealed solar lentigo, early macular seborrheic keratosis, and a focus of inflamed mild solar keratosis. The dermis showed a mild superficial perivascular and interstitial inflammatory infiltrate composed mostly of lymphocytes, histiocytes, and eosinophils. There were occasional melanophages present (Figure 2). Biopsy of the lesion between the breasts revealed inflamed verrucous seborrheic keratosis (Figure 3).

Figure 1. Numerous brown and inflamed papules on the upper abdomen and inframammary area, with 2 tumors on the left inframammary region and mid upper abdomen.

Figure 2. Shave biopsy from the right lateral back showed hyperkeratosis, acanthosis, papillomatosis, and a mild superficial perivascular and lymphohistiocytic inflammatory infiltrate, with mild postinflammatory pigmentary alteration (H&E, original magnification ×4).

Figure 3. Shave biopsy from between the breasts showed hyperplastic epidermis with acuminate papillations covered by orthokeratosis. An inflammatory infiltrate also was present (H&E, original magnification ×20).

We treated the lesion on the right lateral back with cycles of cryotherapy and explained to the patient that the lesion between the breasts was benign. We also reiterated to the patient the importance of wearing sun-protective clothing and UVA/UVB sunblock with a sun protection factor of 30 or higher.

Our patient was diagnosed with pneumonia and subsequently had to discontinue vemurafenib. During the period of nontreatment, the keratotic lesions cleared with postinflammatory hyperpigmentation and no epidermal changes, which showed a possible inference of a direct relationship between the vemurafenib and the appearance of the nonmalignant cutaneous lesions. Although this report only represents 1 patient, other patients possibly can benefit from a modified dose of vemurafenib, which either would resolve or lessen the quantity of these lesions.

Vemurafenib is the first US Food and Drug Administration-approved treatment for nonresectable metastatic melanoma with the BRAF V600E mutation as detected by a US Food and Drug Administration-approved test. 1,2 Mutated BRAF is present in approximately 60% of cutaneous melanomas. 3 Vemurafenib targets the oncogenic BRAF V600E making the protein inactive, thus inhibiting cell proliferation and leading to apoptosis and shrinkage of the metastatic tumors. 3-5 Vemurafenib has a response rate of more than 50% and is associated with rapid improvement in quality of life. 3

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