Rapid cytologic diagnosis of subcutaneous fat necrosis of the newborn.

Subcutaneous fat necrosis of the newborn is a rare self-limited panniculitis that classically presents within the first few weeks of life. The diagnosis is typically clinical, but some cases require skin biopsy with hematoxylin and eosin stain for confirmation. We report a previously undocumented rapid diagnostic protocol that involves collecting a small amount of exudate from a suppurative lesion, placement onto a slide without fixation, and simply viewing the material under a microscope. This novel and practical method of diagnosis reveals doubly refractile crystals diagnostic of subcutaneous fat necrosis without a biopsy, which may be helpful for rapid diagnosis or use in low resource settings.

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion and prominent epidermal involvement: A case report.

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMCT) is a recently described entity with only 13 cases reported in the literature. Histopathologically, the neoplasm consists of atypical epithelioid to spindled cells that form a well-circumscribed nodule usually confined to the dermis and subcutis with cytological features including large vesicular nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry shows variable expressivity of melanocytic markers. Currently, there are limited data regarding long-term outcomes of this newly described entity. Most cases have done well, but there is one case reported with an adverse event. Hence, further studies are needed to accurately classify this tumor. Definitive diagnosis is made by laboratory evidence of CMCT. Herein, we report the first case of CMCT with epidermal involvement in the youngest patient known to be affected to date.

PD-1 blockade induces responses by inhibiting adaptive immune resistance.

Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8(+) T cells (termed adaptive immune resistance). Here we show that pre-existing CD8(+) T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analysed samples from 46 patients with metastatic melanoma obtained before and during anti-PD-1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next-generation sequencing for T-cell antigen receptors (TCRs). In serially sampled tumours, patients responding to treatment showed proliferation of intratumoral CD8(+) T cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8-, PD-1- and PD-L1-expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression after therapeutic PD-1 blockade requires pre-existing CD8(+) T cells that are negatively regulated by PD-1/PD-L1-mediated adaptive immune resistance.

Physical symptoms and psychosocial problems associated with hidradenitis suppurativa: correlation with Hurley stage.

BACKGROUND: Quality of life (QOL) in hidradenitis suppurativa (HS) patients is negatively impacted by physical and psychosocial problems. The aim of this study was to investigate the frequency and severity of HS-specific symptoms and to correlate these with disease severity. Methods We analyzed medical record data from 145 patients seen in an academic HS specialty clinic between August 2009 to March 2018. Results Hurley stage III patients had significantly higher mean Dermatology Life Quality Index (DLQI) scores (20.2) compared to patients with Hurley stage I (11.3) and II (13.9), (P<0.001 and P=0.001, respectively). More than 75% of patients reported physical symptoms of drainage, irritation, pain, itching, bleeding, and odor. There were associated psychosocial problems of embarrassment and self-consciousness. Symptom severity was most strongly correlated with disease severity for odor (correlation coefficient 0.4, P<0.001), difficulty moving arms (0.323, P<0.001), negative impact on job/school (0.303, P<0.001), and negative impact on relationships (0.298, P<0.001). Conclusion Our results highlight the significant burden of HS and the need for a more comprehensive, HS-specific evaluation tool to better assess the QOL of this patient population. Limitations A small cohort in a single academic center.

Squamous cell carcinoma of the perineum masquerading as necrotizing hidradenitis suppurativa.

Many cases of superinfected hidradenitis suppurativa (HS) involve multiple species of bacteria, but gas-producing infections are rare and can complicate the clinical picture. Additionally, recognizing squamous cell carcinoma (SCC) as a complication of longstanding HS is imperative. Herein, we present a unique case of a severe emphysematous HS that was initially mistaken for Fournier gangrene and eventually diagnosed as superinfected SCC.

Initial genome sequencing and analysis of multiple myeloma.

Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-κB signalling was indicated by mutations in 11 members of the NF-κB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.

Erythema Ab Igne: A Clinical Review.

Erythema ab igne (EAI) is a skin condition caused by chronic heat-induced damage. The rash usually progresses over weeks to months of repeated or prolonged exposure to subthreshold-intensity infrared radiation that is not hot enough to cause a burn. The diagnosis is clinical based on patient history and physical examination, but a biopsy can reveal dilated vasculature, interface dermatitis, and pigment incontinence. Erythema ab igne initially was described in association with patients cooking over wood-fire stoves but has been shown over the decades to have a variety of causes. Herein, we describe various etiologies of EAI, including new heat-producing technologies, cultural practices, psychiatric illnesses, and even iatrogenic causes. However, the cause most commonly is application of heat for treatment of chronic pain, which may be a diagnostic clue for an underlying chronic illness. Although there are no current US Food and Drug Administration-approved therapies for treatment of EAI hyperpigmentation, the prognosis is excellent because removal of the heat source often will result in spontaneous resolution over time. Finally, chronic EAI rarely has been reported to evolve into squamous cell carcinoma, poorly differentiated carcinoma, cutaneous marginal zone lymphoma, and even Merkel cell carcinoma.

Orf Virus in Humans: Case Series and Clinical Review.

Ecthyma contagiosum (orf), a worldwide cause of the hand pustule, is caused by orf virus, a member of the genus Parapoxvirus, which causes an epitheliotropic zoonotic infection that spreads from ruminants (even-toed ungulate mammals such as sheep or goats) to humans. Similar members within the poxvirus family can cause a clinically identical viral pustule, which is spread to humans from the respective animal host reservoirs. These entities are impossible to clinically differentiate in the absence of social history or specific polymerase chain reaction studies, though their frequency does vary based on location across the globe.Although its 1-cm solitary hand pustule often is easily diagnosed by the experienced dermatologist, the goal of this review is to expand the understanding of the presentation, differential diagnosis, and treatment of this condition. We present 5 clinical cases of orf. Special care also has been taken to expand on our report of the unique associated cultural and social elements that the expert diagnostician should obtain to determine etiology.Early and rapid diagnosis of this classic condition are critical to prevent unnecessary biopsies or extensive testing, and determination of etiology can be important to prevent reinfection or spread to other humans by the same infected animal.

Isotretinoin in the treatment of hidradenitis suppurativa: a retrospective study.

OBJECTIVE: Isotretinoin has been used off-label in hidradenitis suppurativa (HS) patients with variable results, making it difficult to predict which patients with HS are likely to benefit. MATERIAL AND METHODS: We conducted a retrospective review of HS patients who presented to UCLA HS clinic between August 2009 and March 2018 and collected data on their demographics, reported history of isotretinoin treatment for HS, and treatment response. A number of patient variables were analyzed between the responders and non-responders to see if any were associated with a higher likelihood of a beneficial response. RESULTS: Of the 209 patients, 39 (18.7%) reported prior treatment with isotretinoin. A beneficial response to isotretinoin was reported by 14 (35.9%) patients, while 25 (64.1%) patients reported no response. When comparing responders to non-responders, responders were more likely to have a history of pilonidal cyst (p = .024). Having a concomitant history of regular or cystic acne did not appear to enhance HS treatment response to isotretinoin. CONCLUSIONS: Our data suggest that for HS patients, having a history of pilonidal cyst is associated with a beneficial response to isotretinoin.

A Reticular Rash on the Leg.

A man presented with a nontender, flat rash with pigmentary alteration ranging from light brown to dark brown on his left leg. How would you treat this patient?

Rapidly growing lesions on the forehead.

Three distinct morphologies were visible. Biopsies revealed the diagnosis for each.

Liver Metastasis and Treatment Outcome with Anti-PD-1 Monoclonal Antibody in Patients with Melanoma and NSCLC.

We explored the association between liver metastases, tumor CD8+ T-cell count, and response in patients with melanoma or lung cancer treated with the anti-PD-1 antibody, pembrolizumab. The melanoma discovery cohort was drawn from the phase I Keynote 001 trial, whereas the melanoma validation cohort was drawn from Keynote 002, 006, and EAP trials and the non-small cell lung cancer (NSCLC) cohort from Keynote 001. Liver metastasis was associated with reduced response and shortened progression-free survival [PFS; objective response rate (ORR), 30.6%; median PFS, 5.1 months] compared with patients without liver metastasis (ORR, 56.3%; median PFS, 20.1 months) P ≤ 0.0001, and confirmed in the validation cohort (P = 0.0006). The presence of liver metastasis significantly increased the likelihood of progression (OR, 1.852; P < 0.0001). In a subset of biopsied patients (n = 62), liver metastasis was associated with reduced CD8+ T-cell density at the invasive tumor margin (liver metastasis+ group, n = 547 ± 164.8; liver metastasis- group, n = 1,441 ± 250.7; P < 0.016). A reduced response rate and shortened PFS was also observed in NSCLC patients with liver metastasis [median PFS, 1.8 months; 95% confidence interval (CI), 1.4-2.0], compared with those without liver metastasis (n = 119, median PFS, 4.0 months; 95% CI, 2.1-5.1), P = 0.0094. Thus, liver metastatic patients with melanoma or NSCLC that had been treated with pembrolizumab were associated with reduced responses and PFS, and liver metastases were associated with reduced marginal CD8+ T-cell infiltration, providing a potential mechanism for this outcome. Cancer Immunol Res; 5(5); 417-24. ©2017 AACR.