Joya Sahu

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.

Evaluation of a 1540-nm and a 1410-nm Nonablative Fractionated Laser for the Treatment of Striae.

BACKGROUND Aesthetically, striae distensae (SD) are a source of great concern. No treatment modality is currently considered the gold standard. However, studies of nonablative fractionated lasers (NAFLs) have been promising. OBJECTIVE To evaluate and compare the clinical and histopathologic efficacy and safety of a 1540-nm NAFL and a 1410-nm NAFL for the treatment of SD. METHODS AND MATERIALS Nine patients with abdominal striae were treated for 6 sessions—half of the abdomen was treated with a 1540-nm NAFL whereas the other half was treated with a 1410-nm NAFL. Photographs were taken at baseline and at the 3-month follow-up visit, when subjects were given a questionnaire. Two blinded dermatologists scored the photographs using a pre-established clinical scale. Biopsies were taken from 2 subjects and graded by 2 dermatopathologists using a pre-established pathology scale. RESULTS All 9 subjects demonstrated clinical improvement bilaterally after treatment. Skin biopsies after treatment showed an increase in epidermal thickness, dermal thickness, and collagen and elastin density when compared with baseline. Clinical and histopathological differences between the 2 lasers were not statistically significant. CONCLUSION Treatment with both the 1540-nm and the 1410-nm NAFL was shown to improve SD clinically and histopathologically. Further studies are needed to optimize treatment parameters.

Clinical and histologic characteristics of clinically unsuspected melanomas

Thin melanomas are recognized and captured by clinicians at an alarming rate, whereas thick melanomas remain underrecognized. Improved recognition of thick melanomas will require further understanding of their clinical and histologic characteristics at various stages of development because emerging data suggest that the thin melanomas being captured today may not represent the forerunners of the thick melanomas. In this retrospective analysis, pathology requisition forms from melanomas diagnosed by histopathology were examined for submitted clinical diagnosis, patient characteristics, melanoma thickness, and biopsy method. Three hundred eighty-five melanomas were identified from 2003 to 2011. Most lesions (71.7%) were clinically suspected to be melanocytic. The mean depth in this group was 0.62mm. Of the unsuspected cases (28.3%), the most common submitted diagnoses were basal cell carcinomas and seborrheic keratoses, consistent with previous reports. The mean depth in the unsuspected group was 1.64mm, and more frequently extended to the deep margin (51.8% vs 25.4% of the time). Shave biopsy was the overwhelming preferred method of biopsy (79.5% overall). Compared with thin melanomas, thick melanomas are underrecognized by physicians due to their lack of characteristic morphologic features; consequently, they are more frequently associated with suboptimal biopsies.

Scleroderma renal crisis-like acute renal failure associated with mucopolysaccharide accumulation in renal vessels in a patient with scleromyxedema.

Scleromyxedema is a systemic disease characterized by lichenoid papules, nodules, and plaques on the skin and often diffuse skin induration resembling the cutaneous involvement of systemic sclerosis. The systemic involvement affects the musculoskeletal, pulmonary, cardiovascular, gastrointestinal, and central nervous systems, and the disorder is commonly associated with a paraproteinemia. Involvement of the kidney is rare and not considered a feature of the disease. Here, we describe an unusual case of scleromyxedema complicated by the development of scleroderma renal crisis-like acute renal failure with a marked intimal deposition of mucin, mucopolysaccharides, and hyaluronic acid in the intrarenal vessels.

Origins of the KOH technique

The potassium hydroxide (KOH) procedure is an integral diagnostic procedure, commonly used in daily dermatology practice but with vague origins. Given the many eponyms that exist in dermatology—both for the discovery of a disease and for the pioneering of a technique—it is surprising that no historical consensus exists on the inception of this procedure, nor much scholarly commentary on notable evolutions in technique or utilized materials. Modern dermatology textbooks are notably vague on the matter. Is it because theKOH examination has been considered a largely apprenticed practice—evading widespread description in print and rather kept alive through anecdotal teachings from mentor to trainee? Alternatively, have we technically evolved such that this procedure, with individual adaptations, is largely accepted and practiced in a uniform and systematic manner? The answers seem yes, for contemporary textbook editors provide little detail about the KOH preparation. After its introduction, the KOH examination was received with great aplomb as a novel technique and acquired subsequent modifications to mature into an efficient, diagnostic method of choice. A retrospective exploration of the literature appears to confirm the former, although the

Contiguous verrucous proliferations in syringocystadenoma papilliferum: A retrospective analysis with additional evaluation via mutation-specific BRAFV600E immunohistochemistry

Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal proliferation. There have been several reports describing collision lesions of SCAP and verruca, although little is known about the frequency of this association. Molecular testing has revealed the BRAFV600E mutation in a large proportion of SCAP cases, although its expression pattern has not been previously evaluated.

Clinical and histopathological features of cutaneous manifestations of adult‐onset Still disease

Adult‐onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon‐pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in 2 Asian women are highlighted accompanied by a relevant review of the disease.

Acquired Brachial Cutaneous Dyschromatosis in a 60-Year-Old Male: A Case Report and Review of the Literature

Acquired brachial cutaneous dyschromatosis is an acquired pigmentary disorder that has been described in only 20 patients but likely affects many more. This case of a man with acquired brachial cutaneous dyschromatosis is unique as most reports are in women. We report the case of a 60-year-old male who presents with an asymptomatic eruption characterized by hyperpigmented and telangiectatic macules coalescing into patches on the bilateral extensor aspects of the forearms which is consistent clinically and histopathologically with acquired brachial cutaneous dyschromatosis. Given its presence in patients with clinical evidence of chronic sun exposure and its histopathological finding of solar elastosis, acquired brachial cutaneous dyschromatosis is likely a disorder caused by cumulative UV damage. However, a possible association between angiotensin-converting enzyme inhibitors and acquired brachial cutaneous dyschromatosis exists. Further investigation is needed to elucidate both the pathogenesis of the disorder and forms of effective management. Treatment of the disorder should begin with current established treatments for disorders of dyspigmentation.

APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa

Early-onset squamous cell carcinoma in recessive dystrophic epidermolysis bullosa patients is characterized by APOBEC mutagenesis. Mutational signature sleuthing Individuals with the inherited skin disease recessive dystrophic epidermolysis bullosa (RDEB) are predisposed to developing aggressive squamous cell carcinomas (SCCs), although why this patient group is prone to these cancers at such early ages is unknown. Cho et al. sequenced multiple RDEB SCC tumors and found that the mutation profile in these carcinomas was most consistent with APOBEC-associated mutagenesis, unlike other types of SCC that may be driven by ultraviolet light or tobacco smoke exposure. This finding could open up new lines of thinking on how to successfully prevent or target SCCs in RDEB patients. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin and mucous membrane fragility disorder complicated by early-onset, highly malignant cutaneous squamous cell carcinomas (SCCs). The molecular etiology of RDEB SCC, which arises at sites of sustained tissue damage, is unknown. We performed detailed molecular analysis using whole-exome, whole-genome, and RNA sequencing of 27 RDEB SCC tumors, including multiple tumors from the same patient and multiple regions from five individual tumors. We report that driver mutations were shared with spontaneous, ultraviolet (UV) light–induced cutaneous SCC (UV SCC) and head and neck SCC (HNSCC) and did not explain the early presentation or aggressive nature of RDEB SCC. Instead, endogenous mutation processes associated with apolipoprotein B mRNA-editing enzyme catalytic polypeptide–like (APOBEC) deaminases dominated RDEB SCC. APOBEC mutation signatures were enhanced throughout RDEB SCC tumor evolution, relative to spontaneous UV SCC and HNSCC mutation profiles. Sixty-seven percent of RDEB SCC driver mutations was found to emerge as a result of APOBEC and other endogenous mutational processes previously associated with age, potentially explaining a >1000-fold increased incidence and the early onset of these SCCs. Human papillomavirus–negative basal and mesenchymal subtypes of HNSCC harbored enhanced APOBEC mutational signatures and transcriptomes similar to those of RDEB SCC, suggesting that APOBEC deaminases drive other subtypes of SCC. Collectively, these data establish specific mutagenic mechanisms associated with chronic tissue damage. Our findings reveal a cause for cancers arising at sites of persistent inflammation and identify potential therapeutic avenues to treat RDEB SCC.

Overexpression of Desmoglein 2 in a mouse model of Gorlin syndrome enhances spontaneous basal cell carcinoma formation through STAT3-mediated Gli1 expression

Activation of the hedgehog pathway is causative of virtually all sporadic and Gorlin syndrome-related basal cell carcinomas (BCCs), with loss of function of Ptc1 being the most common genomic lesion. Sporadic BCCs also overexpress Dsg2, a desmosomal cadherin normally found in the basal layer. Using a mouse model of Gorlin syndrome (Ptc1+/lacZ mice), we found that overexpressing Dsg2 in the basal layer (K14-Dsg2/Ptc1+/lacZ mice) or the superficial epidermis (Inv-Dsg2/Ptc1+/lacZ mice) resulted in increased spontaneous BCC formation at 3 and 6 months, respectively. The tumors did not show loss of heterozygosity of Ptc1, despite high levels of Gli1 and phosphorylated Stat3. A panel of sporadic human BCCs showed increased staining of both Dsg2 and phosphorylated Stat3 in all nine samples. Overexpression of Dsg2 in ASZ001 cells, a Ptc1-/- BCC cell line, induced Stat3 phosphorylation and further increased Gli1 levels, in both an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells but not in HaCaT cells. Conversely, stimulation of Stat3 in ASZ001 cells with IL-6 increased Gli1 expression. Our results indicate that Dsg2 enhances canonical hedgehog signaling downstream of Ptc1 to promote BCC development through the activation of phosphorylated Stat3 and regulation of Gli1 expression.