The role of reflectance confocal microscopy in differentiating melanoma in situ from dysplastic nevi with severe atypia: A cross-sectional study.

BACKGROUND: Melanoma in situ and dysplastic nevi with severe atypia present overlapping histopathologic features. Reflectance confocal microscopy findings can be integrated with the dermatopathology report to improve differentiation between melanoma and dysplastic nevi with severe atypia. OBJECTIVE: To compare prevalence of reflectance confocal microscopy findings between melanoma in situ and dysplastic nevi with severe atypia. METHODS: This retrospective observational study compared reflectance confocal microscopy findings in dermatopathologically diagnosed dysplastic nevi with severe atypia and melanoma in situ, collected between 2007 and 2017 at a private pigmented-lesion clinic. Concordant pathologic diagnosis was defined as unanimous agreement between 3 dermatopathologists who independently reviewed all cases; all other cases were classified as discordant. RESULTS: The study included 112 lesions, 62 concordant melanomas in situ, 28 concordant dysplastic nevi with severe atypia, and 22 discordant lesions. In comparing reflectance confocal microscopy findings in concordant cases, melanoma in situ showed more frequently than dysplastic nevi with severe atypia the presence of epidermal atypical melanocytes as round cells (19/62 vs 0/28; P < .001) and dendritic cells (50/62 vs 6/28; P < .001), as well as a diffuse distribution of epidermal atypical melanocytes (50/54 vs 3/6; P = .002). In contrast, dysplastic nevi with severe atypia showed the presence of dense melanocytic nests more frequently than melanoma in situ did (15/28 vs 14/62; P = .003). LIMITATIONS: The study was based on a limited number of lesions originating from a single clinic. CONCLUSIONS: Reflectance confocal microscopy findings may help differentiate a subset of dysplastic nevi with severe atypia from melanoma in situ.

Dupilumab Treatment for Prurigo Nodularis and Pruritis

Prurigo nodularis (PN) is a disease in which chronic scratching and picking of the skin due to intense pruritis results in papulonodules, notably in areas that are accessible to the patient. The pathophysiology is hypothesized to be mediated by a Th2 helper cell response, similar to that seen in atopic dermatitis, therefore, treatment of PN with dupilumab would be expected to elicit a therapeutic response. We demonstrated that treatment of PN with dupilumab significantly decreased pruritis and the size and number of new lesions after 2 months of treatment. J Drugs Dermatol. 2019;18(9):940-942.

A quantitative comparison between SOX10 and MART-1 immunostaining to detect melanocytic hyperplasia in chronically sun-damaged skin.

Histologic differentiation of melanoma in situ (MIS) from solar keratosis on chronically sun-damaged skin is challenging. The first-line immunostain is usually MART-1/Melan-A, which can exaggerate the epidermal melanocytes, causing a diagnostic pitfall for MIS. By comparing MART-1 and SOX10 immunostaining, we scored the percentage of epidermal melanocytes per 2-mm diameter fields in pigmented actinic keratosis (n = 16), lichenoid keratosis (n = 7), junctional melanocytic nevus (n = 6), keratosis with atypical melanocytic proliferation (n = 17) and MIS (n = 10). These cases represented an older population (68 years median age) and the head and neck (50%) was the most common anatomic site. MART-1 score was significantly higher than SOX10 (P value <.05) in solar keratoses, but showed no difference in detecting melanocytic proliferations, demonstrating their equal detection rate of melanocytes. The sensitivity of both MART-1 and SOX10 was 100%, while their specificities were 17% and 96%, respectively. These results show that SOX10 is more specific than MART-1 in distinguishing epidermal melanocytes on sun-damaged skin by avoiding overdiagnosis of melanoma.

Paired comparison of the sensitivity and specificity of multispectral digital skin lesion analysis and reflectance confocal microscopy in the detection of melanoma in vivo: A cross-sectional study.

BACKGROUND: Several technologies have been developed to aid dermatologists in the detection of melanoma in vivo including dermoscopy, multispectral digital skin lesion analysis (MDSLA), and reflectance confocal microscopy (RCM). To our knowledge, there have been no studies directly comparing MDSLA and RCM. OBJECTIVE: We conducted a repeated measures analysis comparing the sensitivity and specificity of MDSLA and RCM in the detection of melanoma (n = 55 lesions from 36 patients). METHODS: Study patients (n = 36) with atypical-appearing pigmented lesions (n = 55) underwent imaging by both RCM and MDSLA. Lesions were biopsied and analyzed by histopathology. RESULTS: RCM exhibited superior test metrics (P = .001, McNemar test) compared with MDSLA. Respectively, sensitivity measures were 85.7% and 71.4%, and specificity rates were 66.7% and 25.0%. LIMITATIONS: The sample size was relatively small and was collected from only one dermatologist's patient base; there was some degree of dermatopathologist interobserver variability; and only one confocalist performed the RCM image evaluations. CONCLUSION: RCM is a useful adjunct during clinical assessment of in vivo lesions suspicious for melanoma or those requiring re-excision because of high level of dysplasia or having features consistent with an atypical melanocytic nevus with severe cytologic atypia.

Herpes zoster granulomatous dermatitis: histopathologic findings in a case series.

Several types of cutaneous reactions have been reported to arise at the site of herpes zoster (HZ) infection weeks to years after the acute disease. Among these, granulomatous reactions are the most frequently reported. In this study, we describe the spectrum of histopathologic findings of HZ granulomatous reactions observed in 26 patients with cutaneous lesions confined to the area of previous HZ eruption and compare them with biopsy specimens taken from 25 patients with acute HZ. All patients with persistent reactions from whom history was available presented within 12 weeks of the onset of the acute eruption. The most frequent findings were interstitial granulomatous dermatitis with lymphocytes, histiocytes and multinucleated giant cells displaying elastophagocytosis and a perineural, perivascular and perieccrine mononuclear inflammatory infiltrate rich in lymphocytes and plasma cells. Less common features included intra-arrector and peri-arrector pili granulomas, follicular dilatation and hyperkeratosis, and vasculitis. Specimens from patients with acute HZ were found to have small numbers of perineural plasma cells and most had subtle granulomatous inflammation, in patterns similar to the group with late granulomatous reactions. Our findings suggest that granulomatous reactions to varicella zoster virus represent a persistent evolving inflammatory reaction after acute infection.

Nodular cystic fat necrosis with calcification in a patient with juvenile dermatomyositis.

Nodular cystic fat necrosis is a rare, benign form of encapsulated fat necrosis with distinct histology, characterized by cystic fat necrosis with lipomembranous changes and, in later stages, calcification. We report the case of a 7-year-old child with juvenile dermatomyositis who presented with three asymptomatic, firm, mobile nodules on the arms and neck. Histology was consistent with nodular cystic fat necrosis with prominent calcification. This is an unusual presentation of this entity because it has never been previously reported in association with juvenile dermatomyositis.

Lymphoma involvement of the eyelid and eye.

Lymphomas of the eye and ocular adnexa are rare lymphoproliferative diseases of the ocular and ocular adnexal tissue. The incidence of these diseases has been rapidly increasing over the past few decades. The exact pathogenesis remains unknown, but it is postulated to be multifactorial and includes genetic aberrations, epigenetic and environmental factors, infectious agents, and chronic antigenic stimulation. The majority of ocular and ocular adnexal lymphomas are of B-cell origin, except for eyelid lymphomas, which are more often of T-cell type. Lymphoproliferative diseases of ocular and ocular adnexal structures are either primary, when they arise in the eye, orbit, lacrimal gland, eyelid, and/or conjunctiva, or secondary extranodal manifestation of systemic lymphoma. Diagnosis is challenging and requires a multidisciplinary approach involving ophthalmologists, dermatologists, oncologists, and radiation oncologists.

Cutaneous vulvar metastases in a patient with anal squamous cell carcinoma.

Metastatic disease of the skin can be difficult to diagnose, particularly when lesions occur in unusual anatomic locations. We report the case of an 80-year-old woman with a history of anal squamous cell carcinoma (SCC) who developed genital ulcers. Biopsy of the lesions revealed features consistent with metastatic SCC. Cutaneous metastases are an infrequent cause of genital ulcerations, and it is important for physicians to consider this entity when evaluating genital ulcers in patients with prior malignancies.

Nutrition and youthful skin.

Nutrition and dietary supplements have been used to promote a youthful appearance for millennia. Despite high public demand for these products, evidence supporting their efficacy is limited and often inconsistent. We discuss the structural and functional changes that occur in the skin during the aging process. We also review evidence supporting the use of nutritional supplements commonly used to promote a youthful appearance, including essential fatty acids, coenzyme Q, collagen peptides, curcumin, polyphenols, flavonoids, probiotics, silymarin, and vitamins A, C, D, and E. We also consider the role of advanced glycosylated end products, antiinflammatory diets, and caloric restriction in delaying premature skin aging. Although evidence supporting the use of some dietary interventions is promising, further long-term studies in humans are required to fully understand their effects on the promotion of a youthful appearance.

The skin microbiome and the gut-skin axis.

The microbiome plays a significant role in human health, homeostasis, immune system, and disease pathogenesis. Disrupted communication between the microbiome and host has been extensively studied in gastrointestinal diseases. To a lesser extent, there is emerging research on the skin microbiome and its connection with the gut, referred to as the gut-skin axis and its effects on dermatologic conditions. A basic overview will be provided of the gut and skin microbiome with a focus on the impact of this connection on cutaneous diseases, such as psoriasis, atopic dermatitis, rosacea, acne vulgaris, photoaging, and cutaneous wounds. In addition, we shall discuss nutrition-based approaches mediated through the gut-skin axis and topical treatments that could serve as potential adjunctive management by manipulation of the microbiome. In particular, there is a growing body of research on oral probiotics, prebiotics, and dietary modifications that may help improve symptoms for a variety of dermatologic conditions in select demographic groups.

Complete response of penile mycosis fungoides with systemic brentuximab therapy.

Mycosis fungoides with penile involvement is extremely rare. Previous reports have shown successful treatment with imiquimod or a combination of beam radiation and chemotherapy. We present a patient with mycosis fungoides and penile involvement. The penile lesions were initially treated with topical imiquimod; however, he developed worsening glandular lesions and discharge. Therefore the treatment was discontinued. Subsequent treatment with brentuximab (anti-CD30) targeted therapy resulted in complete resolution of the penile lesions. To our knowledge, this represents the first case of a complete penile mycosis fungoides response to brentuximab therapy. Brentuximab may be considered for refractory penile mycoses fungoides.

A case of CD30+ nasal natural killer/T-cell lymphoma.

Extranodal nasal natural killer (NK)/T-cell lymphoma is a very rare lymphoma characterized by strong association with Epstein-Barr virus infection, very aggressive clinical behavior, and poor prognosis. The typical phenotype of neoplastic natural killer cells in this entity is as follows: CD2+, CD56+, surface CD3-, cytoplasmic CD3epsilon+, and cytotoxic granule-associated protein positive. CD30 expression, a phenotype characteristic of anaplastic large-cell lymphomas, is not a typical feature of nasal NK/T-cell lymphomas. We describe the case of a 42-year-old woman with chronic nasal congestion and septal deviation who presented with progressive generalized tender erythematous plaques. A skin biopsy revealed an atypical angiocentric mononuclear cell infiltrate. Strong CD30 and CD3e immunoreactivities were noted in large atypical mononuclear cells within the infiltrate initially suggestive of a CD30+ T-cell lymphoma. However, flow cytometry of the skin lesion indicated that the cells were CD2+, CD4-, CD8-, and lacked surface CD3 more typical of a neoplasm of natural killer cells. Further studies revealed that the cells were CD56+, T-cell-restricted intracellular antigen-1+, and contained Epstein-Barr virus sequences consistent with a nasal-type NK/T-cell lymphoma. High titers of Epstein-Barr virus in the blood, evidence of sinonasal disease, and absence of a T-cell receptor gene rearrangement were additional features consistent with the diagnosis. The patient had a very aggressive clinical course and, despite combination chemotherapy, died 8 months after the onset of skin lesions. This case represents an example of nasal-type NK/T-cell lymphoma with expression of CD30. When presenting in the skin, the phenotypic and morphologic features of this lymphoma may lead to an erroneous diagnosis of a CD30+ large-T-cell lymphoma.

A case of Churg-Strauss syndrome associated with antiphospholipid antibodies.

Churg-Strauss syndrome (CSS) is a systemic vasculitis affecting both small- and medium-sized blood vessels, almost invariably affecting the lung, and frequently associated with cutaneous involvement. Microvascular vaso-occlusion leading to digital gangrene is not a feature of CSS. We report an unusual case of a patient with CSS with antiphospholipid antibodies who developed severe digital gangrene in addition to cutaneous vasculitis. The presence of antiphospholipid antibodies is not a feature usually seen in association with CSS. While the full clinical spectrum of CSS is still being defined, the identification of additional features associated with this syndrome might help to better understand the pathogenesis of the disease and to have an impact on both management and prognosis.

Granulomatous diseases: Kids are not just little people.

Granulomatous diseases represent a heterogeneous group of conditions characterized by histiocytic inflammation that affect patients of any age. These diseases differ widely in their pathogenesis and include infectious and noninfectious conditions. This review focuses on noninfectious granulomatous conditions, with particular emphasis on age-related differences in the onset, epidemiology, clinical manifestations, prognosis, and age-specific management of specific granulomatous disorders. Knowledge of age-specific aspects of granulomatous conditions in adults and children improves both the extent of the diagnostic workup and the management of these patients.

Decreased T-cell receptor excision circles in cutaneous T-cell lymphoma.

PURPOSE: The T cell repertoire in patients with advanced cutaneous T cell lymphoma (CTCL) is significantly contracted despite the presence of relatively normal absolute numbers of T cells. We propose that many normal T cells were being lost in patients with CTCL, with the remaining normal T cells expanding clonally to fill the T cell compartment. T-cell receptor excision circles (TREC) form as a result of the initial gene rearrangement in naïve T cells. Although they are stable, they do not replicate and are subsequently diluted with the expansion of a population of T cells. Their concentration is therefore a measure of unexpanded naïve T cells relative to T cells that have undergone expansion. EXPERIMENTAL DESIGN: We analyzed TRECs from unfractionated peripheral blood T cells from 108 CTCL patients by quantitative PCR. In patients with obvious peripheral blood involvement, we also analyzed TRECs from clonal and nonclonal T cells. RESULTS: We found a decrease in the number of TRECs in peripheral blood of patients with CTCL at all stages of disease, and this decrease was proportional to the loss of complexity of the T cell repertoire as measured by complementarity-determining region 3 spectratyping. In patients with leukemic CTCL and a numerically expanded clone, we also found a significantly lower-than-expected number of TRECs in the nonclonal normal T cells. CONCLUSIONS: We hypothesize that the nonmalignant T cells have proliferated to fill the empty T cell repertoire space left by the loss of other T cells, leading to diminished TRECs and loss of T-cell receptor diversity.

Down-regulation and antiproliferative role of C/EBPalpha in lung cancer.

The transcription factor, CCAAT/enhancer binding protein alpha (C/EBPalpha) is important in the terminal differentiation of granulocytes, hepatocytes, and adipocytes, and recurrent mutations of C/EBPalpha were described in acute myeloid leukemia. In the lung, C/EBPalpha is expressed in bronchial cells and type II pneumocytes. Abnormal proliferation of the latter cell type was reported in C/EBPalpha knockout mice. We determined the expression of C/EBPalpha by Northern blot analysis in 30 lung cancer cell lines and found significant down-regulation in 24 cell lines. Immunohistochemical study of primary tumor specimens showed undetectable or low expression of C/EBPalpha in 23 of 53 specimens. Its expression was more frequently down-regulated in adenocarcinoma and poorly differentiated cancer specimens than in squamous cell cancers. A higher frequency of reduced expression was found in more advanced stages. To investigate the consequences of C/EBPalpha expression in lung cancer cells, we stably transfected two cell lines that do not express the gene (Calu1 and H358) with a plasmid allowing for induction of C/EBPalpha protein expression. Induction of C/EBPalpha led to significant growth reduction attributable to proliferation arrest, morphological changes characteristic of differentiation, and apoptosis. These results suggest that C/EBPalpha is down-regulated in a large proportion of lung cancers and that it has growth-inhibitory properties in airway epithelial cells. Genetic analysis of the C/EBPalpha gene is in progress to fully evaluate its role as a novel tumor suppressor in lung cancer.