Intraneural Melanoma Identified With MART-1 Immunostaining in Mohs Micrographic Surgery.

Mohs micrographic surgery (MMS) utilizing melanoma antigen recognized by T-cells (MART-1) immunostaining is an increasingly common method of treatment for minimally invasive melanoma in anatomically constrained areas such as the face, ears, or acral sites. Neurotropic melanoma, also known as neurotrophism in melanoma, refers to the invasion of melanoma cells into the nerves. As such, these tumors can extend well beyond anticipated clinical tumor margins which can increase the risk of local recurrence. Here, we present a case of neurotropic melanoma successfully identified during MMS using MART-1 immunostaining, which was then confirmed with permanent sectioning.

Tranexamic Acid Prevention of Hemorrhagic Complications Following Interpolated Flap Repair: A Single-Center, Retrospective, Cohort Study.

BACKGROUND: Tranexamic acid (TXA) is increasingly being used to prevent hemorrhagic complications after dermatologic surgery. Interpolated flap repairs following Mohs micrographic surgery are at risk for increased bleeding events and unplanned health care utilization, particularly among patients on antithrombotic medication. OBJECTIVE: To assess bleeding events after interpolated flap repair in patients receiving TXA compared with those who did not. MATERIALS AND METHODS: A retrospective review identified interpolated flap repairs in a 5-year period. Hemorrhagic complications were analyzed, defined as major bleeding events, which included all unplanned medical visits, and minor bleeding events, which included any unplanned patient phone calls or messages through electronic medical record. RESULTS: One hundred fifteen patients had interpolated flap repair during the 5-year period, of which 21 (18.3%) received TXA postprocedure. Twenty-seven bleeding events were identified in the non-TXA group compared with 1 event in the TXA-treated group. Patients who received TXA were less likely to have had a bleeding event (28.7% vs 4.8%, p < .01). CONCLUSION: Patients undergoing interpolation flap repair were less likely to experience a bleeding event after subcutaneous injection of TXA.

Bilateral Transposition Flaps With Split-Thickness Skin Grafting of Secondary Defects After a Large Mohs Micrographic Surgery Defect With Exposed Calvarium.

Large, full-thickness defects of the scalp create a common reconstructive dilemma following Mohs micrographic surgery. In cases with exposed calvarium, transposition flap(s) followed by split-thickness skin graft(s) to the secondary defect is an effective method of reconstruction that allows for same-day repair, full defect coverage, and good functional outcomes. Herein, we present the reconstruction of a large scalp defect utilizing bilateral transposition flaps followed by split-thickness skin grafts of the secondary defects.

Permanent section margin concordance after Mohs micrographic surgery with immunohistochemistry for invasive melanoma and melanoma in situ: A retrospective dual-center analysis.

BACKGROUND: Mohs micrographic surgery (MMS) for melanoma practices vary among dermatologic surgeons. The implementation of immunohistochemical staining in MMS for melanoma mitigates challenges associated with slide interpretation; however, the reliability of melanoma antigen recognized by T cells 1 (MART-1), the preferred immunostain for melanoma, has yet to be compared with permanent section pathology. OBJECTIVE: To assess concordance rates of MART-1 frozen sections and permanent section pathologic interpretation of melanoma treated with MMS. METHODS: A dual-center retrospective analysis was conducted to collect concordance and demographic data. Chi-square tests were performed for group comparisons of categorical variables. RESULTS: Of the 379 permanent sections sent, 367 were concordant with frozen section pathology for an overall concordance rate of 96.8%. Cases were stratified into indeterminately concordant and indisputably concordant. Twenty-two (6%) of cases were indeterminately concordant, whereas 345 (94.0%) of cases were indisputably concordant. LIMITATIONS: The concordance rate is derived from a comparison of adjacent tissue margins, an inevitable consequence of utilizing 2 techniques. CONCLUSION: To the author's knowledge, this study represents the largest investigation examining concordance rates of MART-1 frozen sections in Mohs for melanoma. High concordance disputes the ongoing need for additional permanent margins when using MART-1 in routine cases.

Cutaneous Squamous Cell Carcinoma Arising in Immunosuppressed Patients: A Systematic Review of Tumor Profiling Studies.

As solid organ transplantation becomes more prevalent, more individuals are living as members of the immunosuppressed population with an elevated risk for cutaneous squamous cell carcinoma (cSCC). Although great progress has been made in understanding the pathogenesis of cSCC in general, little is known about the drivers of tumorigenesis in immunosuppressed patients and organ-transplant recipients, specifically. This systematic review sought to synthesize information regarding the genetic and epigenetic alterations as well as changes in protein and mRNA expression that place this growing population at risk for cSCC, influence treatment response, and promote tumor aggressiveness. This review will provide investigators with a framework to identify future areas of investigation and clinicians with additional insight into how to best manage these patients.

A case of idiopathic acquired leukonychia totalis in a 17-year-old boy.

Whitening of the nail, or leukonychia, can have a wide range of etiologies including genetic disorders, trauma, poisoning, autoimmune disorders, and infections. Here we detail a case of idiopathic acquired leukonychia totalis in a 17-year-old boy. This condition has been reported 13 times in the literature previously, with only young boys being affected. Proper diagnosis may help minimize unnecessary investigations and prevent additional psychological stress over whether an underlying disease is present.

Comorbidity burden on receipt of adjuvant immunotherapy and survival in patients with stage III melanoma: an analysis of the National Cancer Database.

BACKGROUND: Comorbidity burden is associated with development of cancer, stage at diagnosis, and treatment outcomes. We evaluated the association between comorbidity burden, receipt of adjuvant immunotherapy, and survival in patients with stage III melanoma. METHODS: Using the National Cancer Database, we identified 16,906 patients with stage III melanoma who underwent surgery of the primary site. Outcomes included receipt of adjuvant immunotherapy and overall survival; independent variables included Charlson/Deyo comorbidity index (CDI) and receipt of adjuvant immunotherapy. RESULTS: Patients with CDI scores of two or more averaged 30.0% and 30.9% lower adjusted odds of receiving adjuvant immunotherapy relative to patients with a CDI score of zero or one, respectively (P = 0.001 and 0.002, respectively). Longer survival was associated with lower CDI scores (all P < 0.001) and receipt of adjuvant immunotherapy (P < 0.001). Patients who received adjuvant immunotherapy averaged 16.0% lower adjusted risk of death compared to patients who did not (P < 0.001), which was constant within all CDI cohorts. Patients with a CDI score of two or more averaged 53.4% and 39.1% higher adjusted risk of death relative to patients with a CDI score of zero or one (both P < 0.001). CONCLUSION: Greater comorbidity burden was associated with lower receipt of adjuvant immunotherapy; however, adjuvant immunotherapy provided similar survival benefit for patients' irrespective comorbidity burden. Our findings suggest that patients with stage III melanoma who have a greater comorbidity burden may benefit from adjuvant immunotherapy but should not replace careful patient selection by the clinician.

Procalcitonin Perplexity - Prolonged Idiopathic Elevation in Pleomorphic Sarcoma: A Case Report and Review of the Literature.

Historically, elevations in procalcitonin (PCT) have been implicated in medullary thyroid cancer and neuroendocrine tumors. More recently, the trending of PCT has been suggested as a monitor of infection to assess the presence, clearance and eradication of infection, especially in cancer patients. Its increase serves as a marker of bacterial infections. During homeostasis it is produced by most tissues in the body at an extremely low level (<.01 ng/mL) and is often induced by bacterial endotoxins. In cancer patients additional factors influence these levels. Metastasis in particular is linked with relatively higher PCT levels. We present a case of an afebrile patient with undifferentiated pleomorphic sarcoma who underwent 25 cycles of radiation therapy and presented one month later with elevated procalcitonin, lactic acid, and leukocytosis. All infectious work up was negative. Findings were incidental after a hospital visit for dehydration. Leukocytosis and lactic acidosis resolved after four days into the hospitalization. Procalcitonin, however, remained elevated over four months in the range of 2-5 ng/mL. The patient has no findings of metastatic disease. To our knowledge, there has never been a report in the literature describing a prolonged elevation of procalcitonin in a patient with a non-metastatic sarcoma without any signs of infection or any other underlying cause. The elevation of PCT has been noted in patients who suffered burns, trauma, minor and major surgery, and cardiogenic shock in addition to infection. Increases have served as signs of worsening patient outcomes and elevated rate of complications. Trending PCT can help in appropriated antibiotic use as it has been shown to decrease antibiotic use by 2.4 days. PCT trends have been increasing in value making idiopathic elevations found in combination undifferentiated pleomorphic sarcoma an important addition to the literature.

Human Herpesvirus-8 Negative Multicentric Castleman Disease in a Patient with Human Immunodeficiency Virus Treated with Highly Active Antiretroviral Therapy and Chemotherapy.

Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder with a high mortality rate in undiagnosed patients. Traditionally, human immunodeficiency virus (HIV) positive MCD occurs due to infection with human herpes virus-8 (HHV), which is thought to play a role in the pathogenesis of MCD. We present the case of a 49-year-old woman who was referred to our oncology clinic for generalized lymphadenopathy in a waxing and waning pattern for the last four years. She was found to be HIV positive. Here we report a rare case of HIV-positive, HHV-negative MCD that responded to prompt treatment with highly active antiretroviral therapy (HAART) followed by chemotherapy as evidenced by improved CD4+ T cell numbers and reduction in lymphadenopathy. The findings in this HHV seronegative patient may indicate an alteration in the virulence and tropism between HHV and HIV, and further demonstrate the need for continued investigation into the pathogenesis of Castleman disease.

Novel stem cell and gene therapy in diabetic retinopathy, age related macular degeneration, and retinitis pigmentosa.

Degenerative retinal disease leads to significant visual morbidity worldwide. Diabetic retinopathy and macular degeneration are leading causes of blindness in the developed world. While current therapies for these diseases slow disease progression, stem cell and gene therapy may also reverse the effects of these, and other, degenerative retinal conditions. Novel therapies being investigated include the use of various types of stem cells in the regeneration of atrophic or damaged retinal tissue, the prolonged administration of neurotrophic factors and/or drug delivery, immunomodulation, as well as the replacement of mutant genes, and immunomodulation through viral vector delivery. This review will update the reader on aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa and other less common inherited retinal dystrophies. These therapies include the use of adeno-associated viral vector-based therapies for treatment of various types of retinitis pigmentosa and dry age-related macular degeneration. Other potential therapies reviewed include the use of mesenchymal stem cells in local immunomodulation, and the use of stem cells in generating structures like three-dimensional retinal sheets for transplantation into degenerative retinas. Finally, aspects of stem cell and gene therapy in diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and other less common inherited retinal dystrophies will be reviewed.

Accumulation of cytoplasmic CDC25A in cutaneous squamous cell carcinoma leads to a dependency on CDC25A for cancer cell survival and tumor growth.

Despite its documented role in cell cycle regulation, over-expression of the cyclin-dependent kinase activator CDC25A does not consistently correlate with worse cancer patient outcomes or predict successful clinical response to CDC25A inhibition. The current study was undertaken to investigate CDC25A in skin cancer and understand predictors of positive response to CDC25A targeting. CDC25A was increased in human squamous cell carcinoma (SCC) associated with a shift from a primarily nuclear localization in skin to a strong cytoplasmic localization in SCC, a pattern that was reproduced in skin cancer cell lines. Surprisingly, siRNA-targeting or forced expression of CDC25A failed to alter SCC proliferation. Instead, CDC25A suppressed apoptotic cell death in a manner dependent on both its cytoplasmic localization and interaction with 14-3-3. Normal keratinocytes with nuclear localization of the phosphatase were resistant to CDC25A modulation. Additionally, the CDC25A inhibitors Vitamin K3 or NSC663284 were more toxic to SCC than normal keratinocytes, and CDC25A inhibition effectively suppressed skin cancer growth by increasing apoptosis without affecting normal skin biology. These studies provide proof-of-concept evidence for the potential of CDC25A inhibitors for skin cancer treatment and suggest that an assessment of the cytoplasmic localization of CDC25A may be a strategy for identification of skin and other cancers susceptible to CDC25A targeting.