HDAC inhibition prevents transgene expression downregulation and loss-of-function in T-cell-receptor-transduced T cells.

T cells that are gene-modified with tumor-specific T cell receptors are a promising treatment for metastatic melanoma patients. In a clinical trial, we treated seven metastatic melanoma patients with autologous T cells transduced to express a tyrosinase-reactive T cell receptor (TCR) (TIL 1383I) and a truncated CD34 molecule as a selection marker. We followed transgene expression in the TCR-transduced T cells after infusion and observed that both lentiviral- and retroviral-transduced T cells lost transgene expression over time, so that by 4 weeks post-transfer, few T cells expressed either lentiviral or retroviral transgenes.

Regulatory T-cells in alopecia areata.

Background: Alopecia areata (AA) is believed to have an autoimmune mechanism in which the hair follicles are targeted by CD4+ and CD8+ lymphocytes. Studies investigating the autoimmune mechanism of other cutaneous diseases, including vitiligo, showed that T is a component of cutaneous immune privilege. Our study uses immunohistochemical staining in formalin-fixed, paraffin-embedded tissue to examine the percentage of CD4 FoxP3 , CD25 FoxP3 , and CD8 FoxP3 T in AA in human specimens.

Correction to: Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.

The authors would like to make the following corrections to the published article.

Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.

Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4 and CD8 T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4 and CD8 T cells.

Cutaneous Cytomegalovirus Infection in an Immunocompetent Patient: Innocent Bystander or Culprit?

We present a rare case of cutaneous cytomegalovirus (CMV) infection in a nonimmunocompromised patient. A 74-year-old woman with a history of diabetes presented with an ulcer on the right lateral tibia that occurred at the site of a nerve core biopsy. Subsequent biopsy of the ulcer edge showed granulation tissue with neutrophilic inflammation.

The microenvironment in primary cutaneous melanoma with associated spontaneous tumor regression: evaluation for T-regulatory cells and the presence of an immunosuppressive microenvironment.

Spontaneous tumor regression, regression in the absence of therapeutic intervention, can be identified histologically in over 25% of primary cutaneous melanomas at initial diagnosis. A unique subset of T lymphocytes found in areas of regression can be histologically distinguished from tumor-infiltrating T lymphocytes (TIL) found in areas of tumor progression. We call this unique subset of T lymphocytes regression-associated T lymphocytes (RATs).

Changing Dermatopathology Protocols for Processing Small Skin Biopsies: Decreases in Slide Quantity Does Not Affect Patient Care and Allows for Optimal Efficiency.

In dermatopathology, no standard protocol exists for processing small biopsy specimens. In our original protocol, 2 routine initial slides per biopsy were prepared. For 1003 biopsies, we noted how often the second slide helped in diagnosis or eliminated the need for additional deeper sections.

Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option.

Actinic Keratosis, Transected: What Lies Beneath?

Evaluation of superficial transected shave biopsies of squamous neoplasms often presents a diagnostic dilemma for the dermatopathologist because of the lack of complete visualization of the base of the epidermis. Fear of "missing" an invasive carcinoma must be balanced with avoidance of overdiagnosis of precancerous actinic keratosis (AK), especially on cosmetically sensitive areas such as the face. If a concern exists that a more invasive component may be present, a diagnosis of AK transected at the base (AKT) will often be rendered to alert the dermatologist of this concern.

Targeting Fyn in Ras-transformed cells induces F-actin to promote adherens junction-mediated cell-cell adhesion.

Fyn, a member of the Src family kinases (SFK), is an oncogene in murine epidermis and is associated with cell-cell adhesion turnover and induction of cell migration. Additionally, Fyn upregulation has been reported in multiple tumor types, including cutaneous squamous cell carcinoma (cSCC). Introduction of active H-Ras(G12V) into the HaCaT human keratinocyte cell line resulted in upregulation of Fyn mRNA (200-fold) and protein, while expression of other SFKs remained unaltered.

Resolution of recalcitrant pyogenic granuloma with laser, corticosteroid, and timolol therapy.

A pyogenic granuloma (PG) is a rapidly growing benign vascular tumor that can be found on the skin or subcutaneous tissue. While some pyogenic granulomas may resolve spontaneously, most have a tendency to bleed easily and require treatment. Current therapeutic modalities include topical imiquimod, cryotherapy, electrodessication, curettage, excision, laser therapy, sclerotherapy, and microembolization.

The effectiveness of annotated (vs. non-annotated) digital pathology slides as a teaching tool during dermatology and pathology residencies.

Background: With today's technology, paraffin-embedded, hematoxylin & eosin-stained pathology slides can be scanned to generate high quality virtual slides. Using proprietary software, digital images can also be annotated with arrows, circles and boxes to highlight certain diagnostic features. Previous studies assessing digital microscopy as a teaching tool did not involve the annotation of digital images.

Unusual clinical presentation of cutaneous angiosarcoma masquerading as eczema: a case report and review of the literature.

An unusual case of cutaneous angiosarcoma clinically mimicking eczema is described. A 98-year-old Caucasian male presented with a 6-month history of a flesh-colored, subcutaneous nodule on his left forehead with contralateral facial erythema and scaling that had been previously diagnosed as eczema. Despite treatments with topical steroids and moisturizers, the condition did not resolve.

Mobile teledermatopathology: using a tablet PC as a novel and cost-efficient method to remotely diagnose dermatopathology cases.

: Dermatopathology has relatively few studies regarding teledermatopathology and none have addressed the use of new technologies, such as the tablet PC. We hypothesized that the combination of our existing dynamic nonrobotic system with a tablet PC could provide a novel and cost-efficient method to remotely diagnose dermatopathology cases. 93 cases diagnosed by conventional light microscopy at least 5 months earlier by the participating dermatopathologist were retrieved by an electronic pathology database search.

The new AJCC guidelines in practice: utility of the MITF immunohistochemical stain in the evaluation of single-cell metastasis in melanoma sentinel lymph nodes.

The American Joint Commission on Cancer 2010 guideline changes recommend all patients with single-cell melanoma metastasis identified by immunhistochemical staining of sentinel lymph nodes to be classified as N1 stage. In this study we evaluated the utility of adding microphthalmia transcription factor (MITF) to our current sentinel node evaluation protocol. Twenty benign lymph nodes from nonmelanoma patients were stained with MITF, MART-1/Melan-A, and HMB-45.

Eosinophilic cytoplasmic inclusion bodies in vesicular multinucleated melanocytes: a clue to the diagnosis of benign melanocytic lesions.

Different types of multinucleated melanocytes have been described in benign and malignant melanocytic lesions. Here we describe a relatively common, though underappreciated, type of multinucleated melanocyte characterized by abundant vesicular and fibrillary-appearing cytoplasm containing one or multiple eosinophilic inclusion bodies. In our experience, these vesicular multinucleated melanocytes with inclusion bodies are invariably seen in nevi of long duration.

Comparison between Langerhans cell concentration in lichen planopilaris and traction alopecia with possible immunologic implications.

Lichen planopilaris and long-standing traction alopecia are both traditionally classified as scarring alopecias. The etiology of lichen planopilaris has not been fully elucidated, although an autoimmune mechanism is generally accepted with Langerhans cell involvement implicated in previous studies. The etiology of traction alopecia is generally considered to be the result of mechanical force with subsequent inflammation without an autoimmune component.