Cutaneous Rosai-Dorfman Disease With Linear Lesions and Monoclonal Gammopathy.

Cutaneous Rosai-Dorfman disease (CRDD), a benign histiocytosis of unknown etiology, typically presents as a solitary or clusters of lesions. Although the histopathology is fairly distinctive, the laboratory abnormalities are not; past reports note elevated erythrocyte sedimentation rate, anemia, and polyclonal hyperglobulinemia. We describe a 61-year-old African American diabetic gentleman who presented with nodules in a linear distribution on the flank. Histopathologic examination of a biopsied nodule revealed a pandermal sheet-like infiltrate of plasma cells and histiocytes, some demonstrating elastophagocytosis and emperipolesis. The lesional histiocytes were S100 and CD68 positive and CD1a negative-findings consistent with a diagnosis of CRDD. Additional laboratory work-up performed 12 weeks after the biopsy was taken revealed an elevated serum κ light chain concentration of 37.26 mg/L (reference range: 3.30-19.40 mg/L), which correlated with an M-protein spike identified as IgG κ proteins per serum protein electrophoresis. Given the difficulty in excising a large area and preexisting diabetes, a course of low-dose methotrexate was selected for therapy with a recommendation of close follow-up for the monoclonal gammopathy. To the best of our knowledge, this is the first report of CRDD associated with a linear distribution of lesions and serum protein electrophoresis-confirmed monoclonal gammopathy.

Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sézary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project.

PURPOSE: In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. PATIENTS AND METHODS: In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. RESULTS: Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. CONCLUSION: Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin.

A comparison of the malignancy incidence among patients with psoriatic arthritis and patients with rheumatoid arthritis in a large US cohort.

OBJECTIVE: To compare the incidence rates of malignancy among patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: We analyzed 2,970 patients with PsA (7,133 patient-years of followup) and 19,260 patients with RA (53,864 patient-years of followup). Using a standardized adjudication process, we identified 40 confirmed malignancies in the patients with PsA and 307 confirmed malignancies in those with RA. Incidence rates were calculated per 100 patient-years. Incidence rate ratios were estimated, with adjustment for age, sex, disease duration, body mass index, disease activity, year of enrollment, and medication use. RESULTS: The overall malignancy incidence per 100 patient-years was similar between patients with PsA and patients with RA (0.56 [95% confidence interval (95% CI) 0.40-0.76] and 0.56 [95% CI 0.50-0.63], respectively). Nonmelanoma skin cancer was the most common type of cancer in the overall cohort, with an incidence rate of 0.21 (95% CI 0.12-0.35) in PsA, and 0.20 (95% CI 0.17-0.24) in RA, with a calculated incidence rate ratio of 1.05 (95% CI 0.61-1.80; P = 0.85). Lymphoma rates were similar in PsA and RA (0.04 [95% CI 0.01-0.12] and 0.04 [95% CI 0.02-0.06], respectively; incidence rate ratio 1.00 [95% CI 0.17-3.11]; P = 0.67). The adjusted incidence rate ratio of malignancy in PsA versus RA was 1.17 (95% CI 0.82-1.69; P = 0.37). CONCLUSION: The incidence rates across malignancy subtypes were similar in the PsA and RA cohorts from a US registry.

Congenital subungual melanocytic nevus with a pseudo-Hutchinson sign.

We describe a 29-year-old woman with congenital melanonychia striata and compound nevus of the right first digit. There was extension of the hyperpigmentation onto the proximal nail fold, even beyond the borders established by the band of melanonychia striata. A dermal plaque with irregular borders and variegated pigmentation was also present over the distal digit extending from the pigmented region of the hyponychium. A limited number of biopsy proven congenital subungual melanocytic nevi have been reported in the literature. Interestingly, we found that the majority of these cases present with longitudinal melanonychia in association with periungual hyperpigmentation, constituting a pseudo-Hutchinson sign. Currently studies evaluating the diagnostic test characteristics of Hutchinson sign are lacking. While Hutchinson sign is traditionally considered a worrisome feature it is certainly not pathognomonic and a malignant cause should not be assumed without thorough assessment.

Malignant melanoma: advances in diagnosis, prognosis, and treatment.

The detection of cutaneous melanoma still largely relies on clinical suspicion, skin biopsy, and histopathologic evaluation. New technologies are being evaluated to bypass the skin biopsy in the detection of melanoma. The quest for reliable biomarkers, with respect to subclinical detection, prognosis, and predicting treatment response, is longstanding and ongoing. New therapies have been developed for metastatic disease, including targeted small molecule inhibitors as well as immune modulators.

Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare.

BACKGROUND: Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment-refractory cutaneous lupus erythematosus (CLE). OBJECTIVES: We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment-refractory patients before and after treatment. METHODS: Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans, and CXCL10, an interferon-inducible chemokine, before and after treatment. Immunophenotyping and measurement of interferon-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. RESULTS: Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells, and regulatory T cells were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of interferon-mediated pathways, regardless of clinical response. LIMITATIONS: Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. CONCLUSIONS: Lenalidomide may have usefulness as therapy for severe, treatment-refractory CLE. However, our preliminary data suggest that lenalidomide may activate T cells and trigger systemic disease in some patients with CLE. We also saw a different histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment-refractory patients will improve our understanding of CLE.

Pharmacologic immunomodulation and cutaneous malignancy in rheumatoid arthritis, psoriasis, and psoriatic arthritis.

OBJECTIVE: It is unclear if skin cancer risk is affected by the use of immunomodulatory medications in rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA). The purpose of this study is to evaluate and summarize the available data pertinent to this question. METHODS: The English language literature on PubMed was searched with a combination of phrases, including "malignancy," "skin cancer," "squamous cell carcinoma," "basal cell carcinoma," "melanoma," "psoriasis," "psoriatic arthritis," and "rheumatoid arthritis" in addition to the generic names of a variety of common immunomodulatory drugs. Relevant articles were identified and data were extracted. RESULTS: In total, 2218 potentially relevant articles were identified through the search process. After further screening, 20 articles relevant to RA were included. An additional 19 articles relevant to either psoriasis or PsA were included as well. RA may be a risk factor for the development of cutaneous malignancy. Treatment with tumor necrosis factor inhibitors increases the rates of non-melanoma skin cancer (NMSC) in RA and psoriasis. This risk doubles when combination methotrexate therapy is used in RA. Methotrexate may increase the risk of malignant melanoma in patients with RA and the risk of NMSC in psoriasis. Cyclosporine and prior phototherapy significantly increase the risk of NMSC. CONCLUSION: RA may potentiate the risk of cutaneous malignancy and therefore dermatologic screening in this population should be considered. The use of immunomodulatory therapy in RA, psoriasis, and PsA may further increase the risk of cutaneous malignancy and therefore dermatologic screening examinations are warranted in these groups. More careful recording of skin cancer development during clinical trials and cohort studies is necessary to further delineate the risks of immunomodulatory therapy.

Focal preauricular dermal dysplasia: report of two cases and a review of literature.

We report two cases of focal preauricular dermal dysplasia and review the available literature. Focal preauricular dermal dysplasia is a form of aplasia cutis congenita in which atrophic skin lesions occur in a stereotypical bilateral distribution in the preauricular region. Although focal preauricular dermal dysplasia and membranous cutis aplasia of the scalp share clinical similarities, focal preauricular dermal dysplasia represents a form of aplasia cutis congenita that is not typically associated with extracutaneous anomalies.