Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient careKeywords: anti-CTLA-4, anti-PD-1, anti-PD-L1, dermatologic toxicities, immune checkpoint antibody Curry JL, Tetzlaff MT, Nagarajan P, Drucker C, Diab A, Hymes SR, Duvic M, Hwu W-J, Wargo JA, Torres-Cabala CA, Rapini RP, Prieto VG. Diverse types of dermatologic toxicities from immune checkpoint blockade therapy. J Cutan Pathol 2017; 44: 158-176.

Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.

Malignant melanoma of the oral cavity is rare, accounting for about 1% to 8% of all melanomas. There have been no prospective studies of melanoma in this location, and all previous papers have reported small numbers of cases or have retrospectively reviewed case reports from the literature. The authors report six new cases and review 171 cases published since the last major review in 1975. The classification of oral melanomas with radial growth phases is discussed.

Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy.

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The human hematopoietic progenitor cell antigen is known as CD34. This antigen is present on normal bone marrow progenitor cells and vascular endothelial cells. We used the monoclonal antibody anti-CD34 and immunoperoxidase staining techniques to evaluate the expression of CD34 in benign and malignant vascular and spindle cell tumors. All of the 42 vascular lesions, except two of three lesions of intravascular papillary endothelial hyperplasia, demonstrated diffuse membraneous staining of moderate to strong intensity of their endothelial cells. Also, normal placentas (five) showed similar staining. All neurofibromas (12), three of five neuromas, and one of four neurilemmomas revealed moderate to strong, diffuse, membraneous staining. Five of eight piloleiomyomas, two of seven angioleiomyomas, and one of five uterine leiomyomas showed focal to diffuse, and weak to moderate, membraneous staining in the smooth muscle component. Six dermatofibrosarcoma protuberans were studied: generalized, strongly positive membraneous staining was present in four. All specimens showed staining of the normal endothelial cells and the cells surrounding the hair follicles (bulge area), sebaceous glands, and eccrine glands. No staining was demonstrated in any of the following fibrohistiocytic tumors: atypical fibroxanthomas (two), fibrous dermatofibromas (23), giant cell tumor of tendon sheath (one), and hemosiderotic dermatofibromas (18). Melanocytic tumors [Spitz nevi (three) and spindle cell superficial spreading malignant melanoma (one)], Merkel cell carcinomas (six), and spindle cell squamous cell carcinomas (two) did not stain with anti-CD34. Glomus tumors (two) and a hemangiopericytoma were also negative except for their vascular channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Relapsing polychondritis is a rare disease most commonly presenting as inflammation of the cartilage of the ears and nose. Auricular chondritis, with red ears resembling infectious cellulitis, is the most common initial finding. Antibodies to type II collagen in cartilage are found, and the earlobes are classically spared. Chronic disease may result in a flabby, droopy ear, cauliflower ear, or saddle nose deformity. Acute involvement of the tracheal cartilage may cause collapse of the airway with obstruction and pulmonary infections. Arthritis may be oligoarticular or polyarticular, most often involving the costochondral junctions. Other manifestations include audiovestibular damage; heart valve disease; and neurologic, ocular, and renal disease. Corticosteroids remain the major treatment. Other therapies include nonsteroidal anti-inflammatory drugs, dapsone, colchicine, azathioprine, methotrexate, cyclophosphamide, hydroxychloroquine, cyclosporine, and infliximab.