Multiple Long-Standing Papules and Nodules on the Left Lower Leg.

A woman in her 60s with long-standing thickening and induration of the legs presented with 1 week of left leg pain. Physical examination results revealed multiple firm skin-colored papules and nodules coalescing to form a large plaque on the anterior aspect of the left lower leg, whereas the right lower leg had diffuse induration and hyperpigmentation. What is your diagnosis?

PET/CT scan and biopsy-driven approach for safe anti-PD-1 therapy discontinuation in patients with advanced melanoma.

BACKGROUND: Limited data exist on safe discontinuation of antiprogrammed cell death protein 1 (PD-1) therapy in responding patients with advanced melanoma. The use of 18fluorodeoxyglucose (18FDG)-PET/CT scan and tumor biopsy for assessment of active disease may be an effective predictive biomarker to guide such treatment decisions. METHODS: A retrospective study of 122 patients with advanced melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anticytotoxic T-lymphocyte-associated protein 4 combination therapy at Georgetown Lombardi Comprehensive Cancer Center was conducted. Uveal melanoma patients and those receiving concurrent experimental therapy were excluded. Baseline characteristics, treatment outcomes, and survival were analyzed. Patients who decided to come off treatment typically after 12 months using CT scan radiographic complete response (CR), 18FDG-PET/CT scan complete metabolic response (CMR) or tumor biopsy of a non-CR/CMR tumor site negative for active disease (possible pathological CR) were identified and compared with patients who discontinued treatment due to toxicity while their disease was in control. Event-free survival (EFS) was assessed from the last dose of anti-PD-1 therapy to progression requiring subsequent treatment (surgery, radiation, and/or systemic therapy) or referral to hospice/death due to melanoma. RESULTS: 24 (20%) patients discontinued treatment by choice with no active disease and 28 (23%) patients discontinued treatment due to toxicity with disease control after 12-month and 4-month median treatment durations, respectively. Similar baseline characteristics were observed between cohorts except higher prior receipt of ipilimumab (29% vs 7%; p=0.036) and fewer BRAF mutant positive disease (17% vs 41%; p=0.064) in patients off treatment by choice. Three-year EFS rates were 95% and 71%, respectively. No significant associations between EFS and sex, disease stage, lactate dehydrogenase elevation, BRAF status, prior systemic therapy, ECOG performance status, presence of brain metastases, or combination versus monotherapy were observed. Tumor biopsies led to alternative management in 3/10 patients due to active metastatic melanoma or second malignancy. CONCLUSIONS: Anti-PD-1 therapy discontinuation after 12 months when no active disease is observed on CT scan, PET/CT scan or tumor biopsy may have low rates of disease relapse in patients with advanced melanoma. Biopsy of residual disease may frequently lead to a change in management. These findings are undergoing validation in the EA6192 trial.

Novel Drugs Implicated in Pigmented Purpuric Dermatoses.

We describe two cases of cutaneous eruptions of pigmented purpuric dermatoses (PPDs) arising after exposure to medications not previously reported in the literature as causing these reactions. Specifically, two women had biopsy-proven PPDs, one after exposure to an over-the-counter iodine supplement marketed as an extract from "Norwegian kelp," and the other after intraocular injections of pegaptanib, a vascular endothelial growth factor inhibitor. The eruption occurred shortly after beginning the medication and resolved upon discontinuation. This highlights the importance of considering over-the-counter and intraocular medications when assessing cutaneous eruptions that may be medication related, such as PPDs.

Role of Immune Status in Chemotherapy-Induced Transient Acantholytic Dermatosis.

A 79-year-old man with a recent diagnosis of acute myeloblastic leukemia received induction chemotherapy with daunorubicin and cytarabine, plus moxifloxacin and fluconazole prophylaxis. Approximately 2 weeks later, an asymptomatic eruption appeared on his trunk. He then developed a neutropenic fever and was started on aztreonam, vancomycin, voriconazole, and amikacin and was transferred to our facility from an outside hospital. Micafungin was subsequently added, and the patient defervesced within a few days.

Molecular Variations in Histologic Subtypes of Basal Cell Carcinoma.

There are many molecular variations in the histologic subtypes of basal cell carcinoma (BCC); Ki67 and Bcl-2 expression differs among them and might relate to their prognostic features. The clinically notable friability and its histologic counterpart, retraction, are dependent on cell-cell adhesion and basement membrane characteristics, which may be altered in different ways depending on the tumor morphology and phenotype. Finally, we discuss the pathogenesis of BCCs and recent molecular advances with a review of new and upcoming molecular-based therapeutics.

Acral manifestations of soft tissue tumors.

This group of biologically diverse entities is united by topographic localization to the hands and feet. Categorizing tumors by body site narrows the differential into a short list of possibilities that can facilitate accurate and rapid diagnosis. The goal of this review is to provide a practical approach to soft tissue tumors of acral locations for clinicians, pathologists, and researchers alike. What ensues in the following text is that tight coupling of the clinical picture and histopathologic findings should produce the correct diagnosis, or at least an abbreviated differential. The salient clinicopathologic, immunohistochemical, and molecular features are presented alongside current treatment recommendations for each entity.

Basal Cell Carcinoma. Part 1: Basal Cell Carcinoma Has Come of Age.

Almost 2 centuries after its recognition, basal cell carcinoma (BCC) remains the most common cancer worldwide, with a 30% overall lifetime risk in the United States and an incidence that continues to increase annually. The increasing incidence of BCC is multifactorial and likely correlates to multiple risk factors, including exposure to both ionizing and UV radiation. Despite its relatively indolent growth, what was once referred to as a rodent ulcer or basal cell epithelioma is now identified as a full-fledged malignancy. The authors describe the societal burden of this disease and characterize its malignant potential, emphasizing associated clinical and histopathologic prognostic features.

Early morphea simulating patch-stage mycosis fungoides.

Morphea is a rare fibrosing condition of the skin and underlying tissues characterized histopathologically by thickened collagen bundles throughout the dermis, loss of adnexal structures, and "fat trapping." In the early stages of morphea, the absence of the fully developed characteristic findings may cause diagnostic confusion for the practicing pathologist. The authors report an unusual case of early morphea misdiagnosed as patch-stage poikilodermatous mycosis fungoides (MF) based on the initial clinical, histopathologic, and molecular findings. However, as time elapsed, well-developed lesions revealed clinical and histopathologic features diagnostic of morphea. The authors report this case to illustrate that lesions of early morphea may simulate MF. Given the similarities in clinicopathologic presentation, dermatologists and dermatopathologists should be cautious not to inadvertently misinterpret early morphea as MF.

Amelanocytic anhidrotic alopecia areata-like phenotype after allogeneic hematopoietic cell transplant.

BACKGROUND: Diffuse alopecia areata or canities subita is a rare variant of alopecia in which hair loss is associated with regrowth of white hairs and possible lightening of the skin. Preferential loss of pigmented hair in this disorder may be related to the melanin pigment system and/or melanocytes. Acquired generalized anhidrosis can be associated with autoimmune disease, cancer, graft-vs-host disease, or medications or can be idiopathic. Extensive anhidrosis may cause hyperpyrexia on exposure to heat, and protection from overheating is essential. OBSERVATIONS: A 38-year-old man with idiopathic autoimmune aplastic anemia developed permanent diffuse skin and hair whitening and generalized anhidrosis after a successful allogeneic hematopoietic stem cell transplant. Results of a histopathologic examination, which has previously not been reported in this disease, demonstrated a complete lack of epidermal and follicular melanocytes and a dense perifollicular and periadnexal lymphocytic infiltrate. CONCLUSIONS: The hair- and skin-lightening phenomena in diffuse alopecia areata may be the result of an overstimulated immune system that targets epidermal and follicular melanocytes. Destruction results in irreversible pigmentary loss of the skin. In a patient with multiple risk factors for anhidrosis, a specific cause may be difficult to determine.

Erlotinib-induced scalp perifolliculitis.

Erlotinib is a highly specific epidermal growth factor receptor tyrosine kinase inhibitor used to treat various metastatic cancers. The most commonly reported side effects in patients receiving erlotinib are dermatitis and diarrhea. The authors present two cases of erlotinib-induced severe scalp perifolliculitis, which is an adverse reaction that has not been reported to date. Both patients developed pustules and thick yellow-green crusted plaques on the scalp within weeks of starting treatment with erlotinib for metastatic non-small cell lung carcinoma. Skin biopsies revealed a perifollicular accumulation of inflammatory cells, lymphocytes, and neutrophils. Both patients were treated with oral doxycycline and achieved complete resolution within 2 to 3 weeks and no recurrence despite continuing the epidermal growth factor receptor tyrosine kinase inhibitor. This is a unique presentation of an erlotinib-induced skin eruption.

Dermatitis herpetiformis. Part I. Epidemiology, pathogenesis, and clinical presentation.

Dermatitis herpetiformis (DH) is an autoimmune disease that is linked to gluten sensitivity and has a clear relationship to celiac disease. Both conditions are mediated by the IgA class of autoantibodies and the diagnosis of DH is dependent on detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH but environmental factors are also important. Typically, young adults present with excoriations only, as the severe pruritus effectively destroys any primary lesions. Based upon our experience with DH and a comprehensive literature review, we provide an update of DH epidemiology, pathophysiology, and clinical presentation.

Nevus versus melanoma: to FISH, or not to FISH.

Fluorescence in-situ hybridization (FISH) has arisen as a novel ancillary test for the pathological diagnosis of melanoma. It is an outgrowth of studies using comparative genomic hybridization, a technique capable of surveying the entire genome for DNA copy number changes. An original report published in 2009 showed high sensitivity (87%) and specificity (95%) for diagnosing melanoma, using a combination of 4 FISH probes that target 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), and chromosome 6 centromere. Since then, a number of studies have been published, supporting the high accuracy of FISH for diagnosing melanoma. In addition, various clinicopathological settings where FISH may be particularly useful are explored. FISH tests for melanoma are now commercially available. Meanwhile, questions have been raised by some about the true diagnostic value of FISH, particularly in melanocytic lesions with ambiguous histopathology. This review will briefly introduce the historical development of FISH for melanoma diagnosis and discuss its diagnostic value as well as its potential limitations at present.

Cold panniculitis following ice therapy for cardiac arrhythmia.

Ice therapy has long been used as first line treatment of supraventricular tachycardia in neonates. We report a case of cold panniculitis developing in a 12-day-old neonate after ice therapy for cardiac arrhythmia. This is the first biopsy-proved case of cold panniculitis following ice therapy for supraventricular tachycardia in a newborn.