BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.

In around 50% of melanomas, the BRAF V600 mutation, resulting in an activation of the MAP kinase pathway, is detected. BRAF inhibitors have shown remarkable activity on the disease. However, efficacy is short-lived in most cases, with a median disease-free survival of 6 months. This short duration of response could be explained by the acquisition of resistance mechanisms. Some cancers show sensitivity to the reintroduction of previously active drugs after disease progression. We carried out a retrospective monocentric study on patients with BRAF V600-mutated melanoma who were rechallenged with BRAF inhibitors that were previously beneficial, but in whom the disease had progressed. Nine patients were included. Five patients showed a subsequent partial response, two showed a dissociated response leading to clinical improvement, and two showed no radiological nor clinical response. Eight patients who received rechallenge BRAF inhibitor had received an intercurrent treatment with ipilimumab. These cases suggest that intermittent treatment with BRAF inhibitors could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials.

Ultrasound-guided core needle biopsy of superficial lymph nodes: an alternative to fine-needle aspiration cytology for the diagnosis of lymph node metastasis in cutaneous melanoma.

To investigate the diagnostic value of ultrasound-guided core needle biopsy (US-CNB) in suspected cases of lymph node metastasis from cutaneous melanoma. All patients with cutaneous melanoma followed in Saint-Louis Hospital between 2006 and 2010 who underwent US-CNB for suspicion of melanoma lymph node metastasis were reviewed retrospectively. Histopathological results of US-CNB samples were classified as melanoma, other malignancy, suspicious, inadequate, or benign. The diagnostic accuracy of US-CNB was assessed by comparison with two reference standards: histopathological examination of the radical lymph node dissection or, when this was not available, clinical and radiological follow-up. The data from 72 US-CNB were analyzed. Forty-four melanomas, 22 benign, three other malignancies, three inadequate samples, and no inconclusive specimens were diagnosed. Seventy-one US-CNB results were confirmed (98.6%). US-CNB achieved high sensitivity, specificity, and positive predictive value (respectively, 97.9, 100, and 100%). No adverse events were reported after the procedure. US-CNB provided a mean tissue volume of 16.7 mm per lymphadenopathy. US-CNB has diagnostic value similar to that of fine-needle aspiration cytology. It represents a reliable alternative method in melanoma lymph node metastasis to avoid surgery in patients who will not benefit from it. US-CNB provides relatively large samples of tissue suitable for comprehensive genomic analyses currently needed for research and personalized care of melanoma patients.

[Eccrine porocarcinoma with Bowenoid changes: a challenging diagnosis of adnexal neoplasm]. / Porocarcinome eccrine bowénoïde : un carcinome annexiel de diagnostic difficile.

Eccrine porocarcinoma is a rare malignant sweat gland tumor, representing less than 0.01% of all cutaneous neoplasms, with eccrin differentiation. Its acrosynringeal origin and physiopathology still remain discussed. The prognosis of this carcinoma is held to be poor with a significant risk of lymph node metastasis and local recurrence. Also, this not specific tumor can be a challenging histological diagnosis, in particular, in Bowenoid variant. We report a case of Bowenoid and keratinizing variant of eccrine porocarcinoma of the left ring finger with pejorative evolution and initial diagnosis of infiltrating squamous cell carcinoma arising in Bowen's disease. The knowledge of these patterns and identification of eccrine differentiation of the tumor are essential for the diagnosis and for adapted therapeutic care.

Vemurafenib-induced neutrophilic panniculitis.

Vemurafenib is a targeted therapy, used in patients with metastatic cutaneous melanoma who carry the BRAF V600E mutation, with a relative reduction of 63% in the risk of death. Several adverse events have been described previously, such as photosensitivity or squamous-cell carcinomas. Two cases of panniculitis have been reported recently with two different selective BRAF inhibitors. We report two cases of neutrophilic panniculitis in patients treated by vemurafenib for a metastatic melanoma. Clinical and biological examinations showed no indications for an immune nor an infectious cause of neutrophilic panniculitis. Thus, we believe that vemurafenib caused this panniculitis. Treatment with vemurafenib was maintained in both patients because of the clinical and radiological tumoral responses. One patient showed spontaneous recovery, whereas the other patient presented several recurrences of panniculitis. We believe that physicians should be aware of this cutaneous side effect of vemurafenib, but it should not lead to discontinuation of this treatment.

Octocrylene, an emerging photoallergen.

BACKGROUND: Octocrylene is a new emerging photoallergen. We report and discuss 50 cases of photoallergic contact dermatitis from octocrylene use and/or positive photopatch test reactions to this UV filter and draw attention to the unexpected association in adults with a history of photoallergic contact dermatitis from ketoprofen. OBSERVATIONS: Patients were divided in 3 groups: group A comprised 11 children; group B, 28 adults with a history of photoallergy from sunscreen products; and group C, 14 adults systematically tested with octocrylene because of a history of photoallergy from ketoprofen. All patients but 3 in group C had positive test reactions to octocrylene. Ten of 11 children in group A and 9 of 28 adults in group B had positive patch test reactions to octocrylene. One child in group A, the other 19 adults in group B, and 11 of 14 adults in group C had positive photopatch test reactions to octocrylene. All adults in group C and 24 of 28 adults in group B had a history of photoallergy from ketoprofen and positive patch test or photopatch test reactions to other allergens that are often positive in patients with photoallergy from ketoprofen, especially fragrance components. CONCLUSIONS: Octocrylene appears to be a strong allergen leading to contact dermatitis in children and mostly photoallergic contact dermatitis in adults with an often-associated history of photoallergy from ketoprofen. Patients with photoallergy from ketoprofen frequently have positive photopatch test reactions to octocrylene. These patients need to be informed of sunscreen products not containing octocrylene, benzophenone-3, or fragrances.

Treatment of early stages of mycosis fungoides with narrowband ultraviolet B. A clinical, histological and molecular evaluation of results.

BACKGROUND: Narrowband ultraviolet B (UVB) phototherapy is increasingly used in mycosis fungoides (MF). OBJECTIVE: We report on the results obtained in a prospective series of early MF patients receiving this therapeutic regimen. METHODS: In total, 22 patients were treated. Therapeutic results were evaluated on clinical, histological and molecular levels. Patients were then submitted to a clinical follow-up. RESULTS: The cumulative number of treatments ranged from 22 to 48 (mean: 29). A complete clinical remission (CCR) was obtained in 18/22 patients, and a partial clinical remission in 4 cases. Complete or partial histological responses were achieved in 9/15 (all in CCR) and 4/15 patients, respectively. The molecular response was evaluated in 12 patients, and a disappearance of the dominant T cell clone in the skin was obtained in only 3 cases. After 4-48 months of follow-up (mean 20.1 months), 7/18 patients in CCR (39%) relapsed. CONCLUSION: Narrowband UVB phototherapy is a well-tolerated treatment of early-stage MF, and its efficiency is maximal in very early stages (Ia). Even though clinical results seem very similar to PUVA through indirect and tentative comparisons with historical series, relapses tend to occur earlier than with PUVA, especially when an incomplete histological or molecular response was achieved.

Urticaria pigmentosa localized on radiation field.

A woman previously treated by radiotherapy for a breast cancer developed urticaria pigmentosa mainly restricted to the irradiation field, without any systemic symptoms. Localized forms of urticaria pigmentosa are exceptional, and their triggering factors are poorly understood. Several hypotheses can be discussed in this peculiar observation, among which a direct role of radiotherapy in the occurrence of cutaneous lesions cannot be ruled out.