Jason B. Lee

Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3

The mechanisms underlying adaptive resistance of melanoma to targeted therapies remain unclear. By combining ChIP sequencing with microarray-based gene profiling, we determined that ERBB3 is upregulated by FOXD3, a transcription factor that promotes resistance to RAF inhibitors in melanoma. Enhanced ERBB3 signaling promoted resistance to RAF pathway inhibitors in cultured melanoma cell lines and in mouse xenograft models. ERBB3 signaling was dependent on ERBB2; targeting ERBB2 with lapatinib in combination with the RAF inhibitor PLX4720 reduced tumor burden and extended latency of tumor regrowth in vivo versus PLX4720 alone. These results suggest that enhanced ERBB3 signaling may serve as a mechanism of adaptive resistance to RAF and MEK inhibitors in melanoma and that cotargeting this pathway may enhance the clinical efficacy and extend the therapeutic duration of RAF inhibitors.

Treatment of spider veins with the 595 nm pulsed-dye laser☆☆☆★

BACKGROUND Previous attempts to treat spider veins with the conventional 585 nm pulsed-dye laser with a 0.5-ms pulse duration have been relatively ineffective. Recently, a new pulsed-dye laser that is tunable from 585 to 600 nm with a pulse duration 3 times longer than previously available lasers has preliminarily been shown to be effective for treatment of spider veins. OBJECTIVE Our purpose was to evaluate the effectiveness of multiple treatments with the tunable long-pulse dye laser in treatment of spider veins of the lower extremity. METHODS Ten female volunteers were treated in two separate areas containing blue or red linear spider veins less than 1.5 mm in diameter. Treatments were administered with the pulsed-dye laser with a 1.5-ms pulse duration and 595-nm light at fluences of 15 and 20 J/cm2, and each subject received a total of 3 treatments at each site, administered at 6-week intervals. Photographs were taken before and 6 weeks after the last treatment. RESULTS Computer-based image analysis showed clearing of more than three fourths of veins after 3 treatments with 15 or 20 J/cm2. Side effects were minimal and the treatments were well tolerated. CONCLUSION The 595 nm, 1.5 ms pulse duration, pulsed-dye laser is safe and effective for treating blue or red spider veins of the lower extremities less than 1.5 mm in diameter in nontanned patients with Fitzpatrick skin types I and II. Multiple treatments improve on the results obtained after a single treatment.

Disfiguring cutaneous manifestation of sarcoidosis treated with thalidomide: A case report

A patient with sarcoidosis was treated with thalidomide for disfiguring and painful steroid unresponsive sarcoidal granulomas of the skin. The duration of the therapy was 14 months, during which time, the skin lesions resolved almost completely. The initial dosage was 200 mg a day, which was increased to 400 mg a day after 4 months. Episodic paresthesia of the finger tips and one lower extremity was the only side effect noted, which resolved promptly after discontinuation of the drug. The dramatic response of sarcoidal granulomas of the skin to thalidomide observed in this patient demonstrates the usefulness of this drug as a possible long-term monotherapeutic or steroid-sparing agent in the treatment of sarcoidosis.

Porokeratosis ptychotropica: A clinically distinct variant of porokeratosis

Porokeratosis represents a spectrum of clinical disease. Multiple variants have been described including porokeratosis ptychotropica, a rare subtype. The clinical presentation of porokeratosis ptychotropica frequently resembles an inflammatory perianal disease. We report a patient with porokeratosis ptychotropica with coexistent disseminated superficial actinic porokeratosis. We review the current literature on porokeratosis ptychotropica including the clinical presentation, histopathology, cause, and pathogenesis of this rare variant of porokeratosis.

Eosinophilic dermatosis of hematologic malignancy

Cutaneous involvement by an eosinophil‐rich process (eosinophilic dermatosis) may be encountered in the setting of various hematologic malignancies, including mantle cell lymphoma, acute monocytic leukemia, acute lymphoblastic leukemia, large cell lymphoma, myelofibrosis and chronic lymphocytic leukemia (CLL). Of the various hematologic malignancies, eosinophilic dermatosis has been most frequently described in association with CLL. Published previously as insect bite‐like reaction and eosinophilic dermatosis of myeloproliferative disease, this rare dermatitis presents as a pruritic, papular and occasionally vesicular eruption associated with an eosinophil‐rich infiltrate histopathologically. Although clinical and histopathologic features are similar to insect bites, affected patients frequently deny a history of insect bites. We report a case of eosinophilic dermatosis of hematologic malignancy in a patient with known history of CLL.

Unilateral congenital linear atrophoderma of the leg.

Abstract:  We report an infant with depressed, hypopigmented, linear plaques of congenital onset on the lower extremity. The lesions were asymptomatic and the child was otherwise healthy. Despite the clinically obvious change in skin texture and color, histopathologic changes were subtle: a biopsy specimen showed hypopigmentation and a decrease in elastic fibers in the papillary and upper reticular dermis. Diagnoses considered included various congenital syndromes, idiopathic atrophoderma of Pasini and Pierini, and especially, linear atrophoderma of Moulin. However, because of the significant clinical and histopathologic differences when compared to the aforementioned entities, our patient appears to have a unique presentation of congenital linear atrophoderma.

Images in clinical medicine. Rumpel-Leede sign.

A 47-year-old woman with a history of abdominal surgery presented with syncope and acute gastrointestinal bleeding. She went to the hospital, and while she was undergoing BP monitoring, a petechial rash was noted on each arm, near the sphygmomanometer cuff.

Dermatoscopy: An overview of subsurface morphology

Within the past two decades, an exponential number of publications have emerged on the topic of dermatoscopy, most, if not all, reporting the benefits of using a dermatoscope. Dermatoscopy has been promoted to be useful in diagnosing not only pigmented skin lesions but also a wide range of skin conditions that are infectious, hamartomatous, and inflammatory in nature. Whether or not dermatoscopy truly has a relevant diagnostic role in such a wide range of skin conditions remains to be proven. The diagnostic technique, however, has fundamentally changed the way pigmented lesions are evaluated by dermatologists, as it offers a more methodical and disciplined approach to evaluate them. This review highlights the contribution of dermatoscopy with respect to morphologic characterization and evaluation of pigmented skin lesions.

The Utility of Dermatoscopy in the Evaluation of Xanthogranulomas

The clinical differential diagnosis of a solitary, well-defined papule or nodule is extensive, and includes dermatofibroma, melanocytic nevus, xanthoma, neurofibroma, cyst, and xanthogranuloma, among other conditions (1). Despite their nonspecific clinical appearance (Fig. 1), xanthogranulomas can be correctly identified with the aid of dermatoscopy. The predominance of lipid-laden histiocytes in fully developed xanthogranulomas (2) renders the characteristic dermatoscopic findings, namely an orange-yellow background with subtle erythematous border, which has been compared with a setting sun (Fig. 2). ‘‘Clouds’’ of paler yellow areas, reported to represent collections of lipid-laden histiocytes located in the superficial dermis (3), may accompany the orange-yellow glow. Additional nonspecific dermatoscopic features that may be present include a subtle pigment network and whitish streaks indicative of foci of fibrosis. While the setting sun sign

Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area

Subungual melanoma is a rare subtype of melanoma that usually originates and spreads from the nail matrix. Because of its poor prognosis and short matrix-to-bone distance, amputation has been traditionally performed. Recently, conservative surgery has been attempted for early subungual melanoma, but the evidence supporting this practice is sparse. As little is known about the progression pattern of subungual melanoma, further advances on the subject may provide better guidance on the optimal surgical approach. Histopathology slides, clinical records, and photographs of 23 cases of subungual melanoma were reviewed. For all cases, each area of the nail unit—proximal nail fold, nail matrix, nail bed, and/or hyponychium—in longitudinal sections was available for histological examination. Growth pattern, dermal invasion, and thickness were assessed in each area of the nail unit. There were five cases of melanoma in situ. Eighteen cases showed dermal invasion in at least one area of the nail unit. There were no cases showing dermal invasion in the nail matrix area only. In four cases, dermal invasion involved areas of the nail unit other than the nail matrix. In 14 cases, dermal invasion involved the nail matrix area as well as other areas of the nail unit. Except for one case, the nail matrix area showed thinner dermal invasion compared with dermal invasion in other areas of the nail unit. In conclusion, dermal invasion of subungual melanoma in the nail matrix area tends to occur later than other areas of the nail unit. Longitudinal incisional biopsy is necessary to accurately evaluate melanoma invasion. The findings of this study suggest that conservative surgical treatment for early subungual melanoma may be justified as the nail matrix area, an area of thin dermis and close proximity to the underlying bone, appears to be more resistant to invasion.