Narrow excision margins are appropriate for Merkel cell carcinoma when combined with adjuvant radiation: Analysis of 188 cases of localized disease and proposed management algorithm.

BACKGROUND: Merkel cell carcinoma (MCC) management typically includes surgery with or without adjuvant radiation therapy (aRT). Major challenges include determining surgical margin size and whether aRT is indicated. OBJECTIVE: To assess the association of aRT, surgical margin size, and MCC local recurrence. METHODS: Analysis of 188 MCC cases presenting without clinical nodal involvement. RESULTS: aRT-treated patients tended to have higher-risk tumors (larger diameter, positive microscopic margins, immunosuppression) yet had fewer local recurrences (LRs) than patients treated with surgery only (1% vs 15%; P = .001). For patients who underwent surgery alone, 7 of 35 (20%) treated with narrow margins (defined as ≤1.0 cm) developed LR, whereas 0 of 13 patients treated with surgical margins greater than 1.0 cm developed LR (P = .049). For aRT-treated patients, local control was excellent regardless of surgical margin size; only 1% experienced recurrence in each group (1 of 70 with narrow margins ≤1 cm and 1 of 70 with margins >1 cm; P = .56). LIMITATIONS: This was a retrospective study. CONCLUSIONS: Among patients treated with aRT, local control was superb even if significant risk factors were present and margins were narrow. We propose an algorithm for managing primary MCC that integrates risk factors and optimizes local control while minimizing morbidity.

Review of Common Alternative Herbal "Remedies" for Skin Cancer.

BACKGROUND: Alternative herbal remedies for skin cancer are commonly found on the Internet. Many websites contain inaccurate or false information regarding side effects and efficacy. OBJECTIVE: To review the evidence behind several commonly advertised herbal remedies that claim to cure skin cancer: black salve, eggplant, frankincense, cannabis, black raspberry, milk thistle, St. John's wort, and turmeric. METHODS: A PubMed search was performed using the common and scientific names of frequently advertised herbal remedies along with the terms "nonmelanoma skin cancer," or "basal cell carcinoma" or "squamous cell carcinoma," or "melanoma." RESULTS: Some preclinical studies have shown positive evidence that these substances can induce apoptosis in skin cancer, but clinical studies proving efficacy are either insufficient, nonexistent, or show negative evidence. Botanicals that were excluded are those that do not have published studies of their efficacy as skin cancer treatments. CONCLUSION: Online advertising may tempt patients to use botanical agents while citing efficacy found in preclinical studies. However, many agents lack strong clinical evidence of efficacy. Dermatologists must be aware of common herbal alternatives for skin cancer treatment to maintain effective patient communication and education.

Fire Safety in Mohs Micrographic Surgery.

BACKGROUND: Surgical fire is a rare event, but one with potentially devastating patient outcomes. OBJECTIVE: This study was conducted to investigate the incidence, risk factors, and outcome of surgical fires experienced by members of the American College of Mohs Surgeons (ACMS). METHODS: An internet survey was developed and sent to ACMS members. Data collected included total years of experience, total number of cases, typical management of supplemental oxygen, and surgical fires experienced. RESULTS: Eighty participants contributed data on 886,200 cases of MMS. Nine surgeons (11%) reported at least 1 surgical fire, yielding an estimated incidence of 1 fire per 88,620 cases (0.001%). The most common site of involvement was the scalp (67%). Common ignition sources included monopolar electrosurgical devices (78%) and battery-powered thermal cautery (22%). Fuel sources included towels or drapes, gauze, isopropyl alcohol, aluminum chloride, hairspray, and diethyl ether. Supplemental oxygen was not involved in any of the cases. Five patients suffered singed hair while 4 patients did not suffer any injuries. None suffered any permanent functional or aesthetic deformities. CONCLUSION: The overall risk of surgical fire in MMS is minimal. However, safety measures and greater awareness of fire risks are necessary to prevent patient harm.

Mohs Mapping Fidelity: Optimizing Orientation, Accuracy, and Tissue Identification in Mohs Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) is a highly effective process that requires consistent accuracy in resection, mapping, and histologic interpretation. Although the general sequence in MMS is similar, there are numerous variations among Mohs surgeons as to how this process is performed. OBJECTIVE: This article aims to review the process of MMS, with the intent to identify and mitigate the potential errors at each step. Existing variations will be discussed and protocols offered to minimize error and optimize accuracy. METHODS: A Pubmed search was performed for publications on methods of tissue mapping, orienting, and processing in MMS. RESULTS: Our literature review highlights various techniques for tissue orientation, transfer, flattening, inking, mapping, and processing of later stages and multiple specimens. We discuss our system, which reduces error during tissue transfer, tissue identification in vivo and ex vivo, and tissue flattening. Furthermore, we discuss adaptations to increase the accuracy during reexcisions of subsequent Mohs layers. CONCLUSION: Variations in MMS reflects the diverse training and creativity among Mohs surgeons. Unless potential errors are addressed, however, false negatives will occur and undermine the superior cure rate of MMS.

Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development.

What pathways specify retinal ganglion cell (RGC) fate in the developing retina? Here we report on mechanisms by which a molecular pathway involving Sox4/Sox11 is required for RGC differentiation and for optic nerve formation in mice in vivo, and is sufficient to differentiate human induced pluripotent stem cells into electrophysiologically active RGCs. These data place Sox4 downstream of RE1 silencing transcription factor in regulating RGC fate, and further describe a newly identified, Sox4-regulated site for post-translational modification with small ubiquitin-related modifier (SUMOylation) in Sox11, which suppresses Sox11's nuclear localization and its ability to promote RGC differentiation, providing a mechanism for the SoxC familial compensation observed here and elsewhere in the nervous system. These data define novel regulatory mechanisms for this SoxC molecular network, and suggest pro-RGC molecular approaches for cell replacement-based therapies for glaucoma and other optic neuropathies.SIGNIFICANCE STATEMENT Glaucoma is the most common cause of blindness worldwide and, along with other optic neuropathies, is characterized by loss of retinal ganglion cells (RGCs). Unfortunately, vision and RGC loss are irreversible, and lead to bilateral blindness in ∼14% of all diagnosed patients. Differentiated and transplanted RGC-like cells derived from stem cells have the potential to replace neurons that have already been lost and thereby to restore visual function. These data uncover new mechanisms of retinal progenitor cell (RPC)-to-RGC and human stem cell-to-RGC fate specification, and take a significant step toward understanding neuronal and retinal development and ultimately cell-transplant therapy.

A review of melasma treatment focusing on laser and light devices.

Melasma is a pigmentary disorder of unclear etiology with numerous treatment options and high recurrence rates. Laser and light therapies may be utilized cautiously as second- or third-line options for recalcitrant melasma, but low-energy settings are preferred due to the risk of postinflammatory hyperpigmentation and melasma stimulation. Commonly used lasers include the low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet laser, nonablative fractionated lasers, and intense pulsed light. Strict sun protection, concomitant use of bleaching agents, and maintenance treatments are necessary. A variety of other treatments that may also help to improve results are now being more widely adopted, including oral tranexamic acid, pulsed dye laser, antioxidants, and laser-assisted drug delivery.

Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions.

Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy.

Combined melanocytic and sweat gland neoplasm: cell subsets harbor an identical HRAS mutation in phacomatosis pigmentokeratotica.

Phacomatosis pigmentokeratotica (PPK) is characterized by the co-existence of epidermal nevi and large segmental speckled lentiginous nevi of the papulosa type. PPK, previously explained as 'twin spot' mosaicism due to the postzygotic crossing-over of two homozygous recessive mutations, has recently been shown to derive from one postzygotic activating RAS mutation. Epidermal nevi, including those in PPK, are known to give rise to neoplasms such as trichoblastoma and basal cell carcinoma. Within speckled lentiginous nevi, Spitz nevi and melanoma have been well documented. We report a case of PPK with a combined melanocytic and adnexal neoplasm presenting where the nevi conjoined. Using next-generation sequencing techniques, we were able to identify the same HRAS G13R mutation within both components of the tumor, and to show the absence of additional mutated modifier genes in a panel of 300 cancer-related genes. Given the genetic findings in this rare tumor-type, we suggest that this case may be used as a model for understanding the development of biphenotypic neoplasia or intratumoral heterogeneity in some cases.

Multicenter case series of indolent small/medium-sized CD8+ lymphoid proliferations with predilection for the ear and face.

We report 7 cases of a CD8 lymphoid proliferation of the ear and face with a cytotoxic T-cell phenotype, but an indolent clinical course. All patients presented with stable or slowly growing asymptomatic lesions on the ear, nose, or lower eyelid. Histopathology showed a dense diffuse dermal infiltrate of small- to medium-sized atypical lymphocytes without destructive features. The lymphocytes were positive for CD3, CD8, ß-F1, and TIA-1 and negative for CD4, CD30, CD56, granzyme B, and PD-1. Of note, the proliferation index was low in available cases. All patients remained in complete remission at median follow-up of 14 months regardless of treatment modality. Staging was negative for extracutaneous disease in all patients. The clinically indolent behavior and histopathologic phenotype together with a low proliferation index (10%-15%) emphasize the importance of accurate diagnosis and appropriate clinical management to avoid overtreatment and complications of therapy.

A case-control study of clinicopathologic features, prognosis, and therapeutic responses in patients with granulomatous mycosis fungoides.

BACKGROUND: Granulomatous mycosis fungoides (GMF) is an uncommon variant of mycosis fungoides (MF). OBJECTIVE: We sought to analyze the relative frequency, clinicopathologic characteristics, prognosis, and therapeutic responses of GMF. METHODS: We conducted a retrospective case-control study of patients with GMF and age- and stage-matched patients with classic MF between 1981 and 2012. RESULTS: A total of 27 patients with GMF were identified, representing 6.3% of all patients with MF at our center. Skin manifestations were similar to classic MF having an atypical lichenoid CD4(+) CD8(-) lymphocytic infiltrate with interstitial histiocytes and/or perivascular granulomas with giant cells. Fewer patients with GMF achieved a partial response or complete response with topical (57% vs 83%; P = .002) or ultraviolet light (62% vs 90%; P = .006) therapy. The 5- and 10-year progression-free survival rates were significantly lower in patients with GMF (59% and 33%) compared with patients with classic MF (84% and 56%; P = .02), but overall survival was similar between groups (86% and 72% vs 85% and 85%; P = .54). LIMITATIONS: The retrospective methodology may underestimate the frequency of GMF. The median follow-up time may be too short to detect possible differences in overall survival. CONCLUSION: More frequent disease progression and poorer response to skin-directed therapies were observed in patients with GMF. Our findings may be helpful in selecting the most appropriate treatment for these patients.

Management of cutaneous T cell lymphoma: new and emerging targets and treatment options.

Cutaneous T cell lymphomas (CTCL) clinically and biologically represent a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the most common subtypes. Over the last decade, new immunological and molecular pathways have been identified that not only influence CTCL phenotype and growth, but also provide targets for therapies and prognostication. This review will focus on recent advances in the development of therapeutic agents, including bortezomib, the histone deacetylase inhibitors (vorinostat and romidepsin), and pralatrexate in CTCL.