Rebecca G. Pomerantz

Mutation of p53 in head and neck squamous cell carcinoma correlates with Bcl‐2 expression and increased susceptibility to cisplatin‐induced apoptosis

The p53 protein, a well‐known tumor suppressor that functions primarily as a transcription factor, initiates cell cycle arrest and apoptosis after genotoxic stress. The antiapoptotic regulator Bcl‐2 is a downstream modulator of p53‐induced apoptosis. Loss of function of the p53 tumor suppressor through mutation is an important event that contributes to cellular transformation. Mutation of p53 is one of the most common genetic alterations in squamous cell carcinomas of the head and neck (SCCHN). We hypothesized that p53 mutation is associated with Bcl‐2 expression and susceptibility to apoptosis in SCCHN.

Infectious agents in cutaneous T-cell lymphoma

Infectious agents have long been suspected as potential causative agents in cutaneous T-cell lymphoma (CTCL). Tissues of patients with CTCL have been evaluated for evidence of infection with a number of agents, including Staphylococcus aureus, retroviruses, and herpesviruses. These studies have failed to reveal a consistent association of CTCL with investigated agents. However, there is substantial evidence suggesting a potential role of a yet unidentified virus in CTCL. This article will review the findings of studies exploring potential roles of infectious agents in CTCL. In addition, we investigated CTCL tissues for evidence of infection with Merkel cell polyomavirus, a novel polyomavirus that was recently discovered as a probable carcinogenic agent in Merkel cell carcinoma. Cutaneous lesions demonstrating mycosis fungoides were stained with a monoclonal antibody against the Merkel cell polyomavirus T antigen, along with appropriate positive and negative controls. Immunohistochemical stains produced negative results in all examined mycosis fungoides specimens. These findings, which suggest a lack of association of CTCL with Merkel cell polyomavirus, add to the current body of knowledge regarding infectious agents and CTCL.

Optical Coherence Tomography Used as a Modality to Delineate Basal Cell Carcinoma prior to Mohs Micrographic Surgery

Optical coherence tomography (OCT) has potential as a modality for in vivo imaging of non-melanoma skin cancer (NMSC). By allowing identification of sub-surface margins of NMSC lesions, the use of OCT could improve the rate of complete excision and reduce the average number of stages during Mohs micrographic surgery (MMS). The objective of this study was to use OCT to delineate the apparent sub-surface margins of NMSC lesions prior to their excision by MMS. Lesions were scanned with reference to a physical marker on the skin, and the apparent margins were then identified from the OCT images and marked on the skin. Photographs of these margins and the Mohs defect were correlated and compared. OCT appears capable of visualizing the transition from lesional to normal tissue. In this case study, margins marked by use of the OCT system before surgery exhibit excellent correlation with the MMS defect. OCT offers the promise of better outcomes by enabling accurate margin mapping of NMSC in advance of MMS. Priorities now are to demonstrate this capability in a larger study, and to understand clearly indications and contraindications for use.

Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies.

The etiology of cutaneous T-cell lymphoma (CTCL) remains unknown, with potential infectious causes having been explored. This contribution evaluates the evidence suggesting an infectious etiology and pathogenesis of the disease, characterizes the relationships between various specific pathogens and CTCL, and discusses some of the difficulties in establishing a causal link between infectious agents and CTCL carcinogenesis. Researchers have evaluated CTCL specimens for evidence of infection with a variety of agents, including human T-lymphotropic virus, Epstein-Barr virus, human herpesvirus-8, and Staphylococcus aureus, although other pathogens also have been detected in CTCL. Although there is significant evidence implicating one or more infectious agents in CTCL, studies to date have not linked definitively any pathogen to disease development, and various studies have yielded conflicting results.

Posttransplant Cutaneous T-Cell Lymphoma Case Reports and Review of the Association of Calcineurin Inhibitor Use With Posttransplant Lymphoproliferative Disease Risk

BACKGROUND Cutaneous T-cell lymphoma occurring in the context of posttransplant immunosuppression is rare, with 27 cases documented to date. OBSERVATIONS We report 2 new cases of posttransplant cutaneous T-cell lymphoma in patients treated at our institution. Both were male recipients of renal transplants who had undergone transplantation a mean of 5.3 years previously and were taking various multidrug immunosuppressive regimens, including cyclosporine, tacrolimus, mycophenolate mofetil, and prednisone. CONCLUSIONS These cases underscore the association of posttransplant cutaneous T-cell lymphoma with renal transplantation, cyclosporine and tacrolimus therapy, male sex, and later onset compared with B-cell posttransplant lymphoproliferative disease. Relative to the general population, the incidence of cutaneous T-cell lymphoma seems increased among transplant recipients receiving immunosuppressive medications.

Novel approach to gene expression profiling in Sézary syndrome

Background  Microarray hybridization studies in Sézary syndrome (SS) have compared T lymphocytes from patients with cutaneous T‐cell lymphoma with those of normal controls; a major limitation of this design is that significant inherent genetic variability of lymphocyte populations between individuals may produce differences in gene expression unrelated to disease state.

Risk assessment in surgical patients: balancing iatrogenic risks and benefits.

Cutaneous procedures are associated with a wide variety of potential risks. This contribution discusses risk-related considerations in the preoperative, intraoperative, and postoperative management of dermatologic surgery patients. In the preoperative setting, major considerations include bleeding risks, the presence of pacemakers or defibrillators, risks of local and systemic infection, and the possibility of adverse reactions to local anesthetics and topical agents used for dermatologic procedures. Risk is minimized intraoperatively through careful attention to sterile technique, maintaining adequate hemostasis, skillful management of emerging complications, and effective closure of surgical defects. To optimize outcomes, postoperative priorities include effective management of postoperative bleeding, appropriate wound care, and prevention and treatment of hypertrophic scars and keloids. Reducing the likelihood of adverse surgical outcomes requires identification of potential risk factors and case-specific approaches to minimize risks while simultaneously preparing for the possibility of complications.

Dendritic Cell Vaccines in Cancer: Obstaclesto Overcome

Significant progress has been made in the development of cancer immunotherapies. However, as advances continue to unravel the complexity of the immune system and processes involved in the induction of antitumor immunity and tolerance, new questions increasingly arise. Various approaches have been undertaken in an effort to induce efficient antitumor immunity. Dendritic cells are the most potent antigen-presenting cells known, and this capacity of dendritic cells has been exploited against various malignancies under different conditions. This chapter reviews various controversies in dendritic cell-based vaccine development, including sources of dendritic cells, their differentiation, maturation and antigen loading, vaccine delivery, as well as effective monitoring of the immune and clinical responses in vivo.

Immunomodulation in Dermatology

B cell-targeting therapies. T cell-targeting therapies. Anti-TNF therapies. Other pathways.