Complete response of Merkel cell carcinoma with talimogene laherparepvec (TVEC) monotherapy.

Merkel cell carcinoma (MCC) is a rare neuroendocrine neoplasm, warranting surgical excision with sentinel lymph node biopsy. In later stages, adjuvant chemotherapy and radiation are required owing to its aggressive malignant behavior. We describe a 62-year-old woman who presented with multifocal recurrence of MCC and was not a candidate for immunotherapy or surgery. The patient underwent four treatments of intratumoral talimogene laherparepvec (TVEC) and demonstrated a complete response with no histologic evidence of remaining MCC on four scouting biopsies. Although TVEC therapy is currently approved for the treatment of advanced stage melanoma, it is still being investigated in MCC. This case supports the use of TVEC as monotherapy in select patients with locally advanced MCC who are not candidates for surgery or systemic immunotherapy.

Surgical Margin Mapping of Melanoma In Situ Using In Vivo Reflectance Confocal Microscopy Mosaics.

BACKGROUND: Melanoma in situ (MIS) can have poorly defined borders and subclinical extension that makes margin control challenging. Reflectance confocal microscopy (RCM) is a promising noninvasive technique that can be used to assess subclinical spread. OBJECTIVE: To optimize surgical margins of histology-proven MIS using RCM mosaics. MATERIALS AND METHODS: Prospective review of 22 patients with histology-proven MIS who underwent RCM margin mapping prior to staged excision, between August 1, 2018, and August 13, 2020, at the Department of Dermatology, University of New Mexico, School of Medicine. RESULTS: Twenty patients (91%) had tumor clearance on the first stage using a 3-mm surgical margin after confocal margin mapping. CONCLUSION: Reflectance confocal microscopy margin mapping using the mosaic device tends to clear MIS in one stage, and the use of the handheld device may improve the accuracy for difficult anatomic areas. Current Procedural Terminology codes for RCM do not reflect the time required and complexity of the procedure. Reflectance confocal microscopy margin mapping prior to excision has the potential to decrease the number of stages needed for melanoma removal, reduce treatment time, and cost.

Reflectance confocal microscopy in pediatric dermatology: A state-of-the-art review.

Reflectance confocal microscopy is an innovative imaging modality, which noninvasively provides an optical image to aid in the diagnosis of skin lesions. While performing a skin biopsy for histopathologic analysis is the gold standard to definitively diagnose skin disease, this may prove to be more difficult in the pediatric population. This will occasionally necessitate sedation or general anesthesia as an approach, which carries a number of different risks. Reflectance confocal microscopy is an exciting new avenue in the support of diagnosing skin pathology, with the goal of improving pediatric patient tolerance and experience when examining epidermal and superficial dermal skin lesions. This review discusses the utility of reflectance confocal microscopy for pediatric dermatology patients pertaining to melanocytic and non-melanocytic skin neoplasms and inflammatory and infectious skin diseases in children.

Cutaneous dystrophic calcification following high-dose radiotherapy for a liposarcoma.

Cutaneous dystrophic calcification as a late change of radiation therapy is a rarely reported finding. Initially, it was almost exclusively described as occurring on the chest wall in breast cancer patients but has since been described in several other malignancies. We describe the first reported case of radiotherapy-induced calcinosis cutis occurring at the site of a previous liposarcoma. Review of the literature including risk factors, similar cases, pathophysiology, and management is also explored.

Dermatologists are more likely than oncologists to prescribe skin-directed therapies for early-stage cutaneous T-cell lymphoma: a retrospective review.

Early-stage cutaneous T-cell lymphoma (CTCL) is managed effectively with skin-directed therapies such as topical medications, phototherapy, and local ionizing radiation. Patients with CTCL often seek care from both dermatologists and oncologists. Our study aimed to compare the frequency that skin-directed treatments were prescribed to patients managed by each of these specialties. Overall, we found there was a statistically detectable relationship between the presence or absence of oncologist involvement and the likelihood that a patient would be prescribed skin-directed therapies (P=0.0003). Of the oncologists included in the study, 66% opted for management revolving around systemic rather than skin-directed therapies. However, when a dermatologist and oncologist worked together in a patient's care, the number of patients receiving skin-directed therapies increased to 100%. Our study suggests that patients with early stage CTCL may benefit from having a dermatologist involved in their care.

BRAF inhibitor and hairy cell leukemia-related transient acantholytic dermatosis.

Grover disease (GD) is an acquired, nonfamilial, nonimmune mediated, transient or persistent acantholytic dermatosis. Herein, we present a 72-year-old man who had clinical and histopathologic findings of GD following two weeks of treatment with vemurafenib without MEK inhibitor. The patient was successfully treated with topical emollients and a high-potency corticosteroid. Meanwhile, vemurafenib was temporarily discontinued. Drug-induced GD has increasingly been reported in patients on BRAF inhibitor monotherapy as an immune-related adverse event. The cutaneous side effects seem to arise secondary to a paradoxical activation of the mitogen-activated protein kinase signaling of BRAF inhibitor treatment, leading to keratinocyte proliferation. Although the pathogenesis of GD has not been delineated, there is suggestion of activation of T lymphocytes, particularly helper cells under the action of pro-inflammatory cytokines, resulting in proliferation of keratinocytes. Combination therapy with a MEK inhibitor appears to prevent BRAF-induced GD. Given that there is a higher prevalence of GD in patients with hematologic malignancy, a direct causal relationship between the initiation of vemurafenib therapy and development of GD in this case may be difficult to establish.

Generalized basaloid follicular hamartoma syndrome versus Gorlin syndrome: A diagnostic challenge.

Basaloid follicular hamartoma is a relatively rare benign neoplasm of follicular origin that can be mistaken histologically for basal cell carcinoma, but hereditary forms of basaloid follicular hamartoma are associated with nevoid basal cell carcinoma syndrome, or Gorlin syndrome. The pathophysiology of basaloid follicular hamartoma development involves mutations in the patched gene, which is also causative in nevoid basal cell carcinoma syndrome. We present a mother and daughter with basaloid follicular hamartomas, with genetic testing confirming patched gene mutation in the daughter.

Moonlighting in residency: a dermatology perspective.

BACKGROUND: Moonlighting refers to the practice of medicine outside one's training institution in exchange for financial compensation. High medical debt-to-income ratios drive residents to seek additional compensation during residency. OBJECTIVE: To gather information to establish the current practices of moonlighting and to better understand the thoughts and experiences of dermatology residency program directors regarding moonlighting. METHODS: All allopathic and osteopathic dermatology residency program directors in the United States and Puerto Rico received a blinded survey between February 1, 2017 and April 1, 2017 through an email link. RESULTS: Response rate was 47.0%. Of the programs that responded, 63.16% allowed moonlighting. In three regions, 100% of programs allowed moonlighting. The geographic area with the lowest percentage of programs permitting moonlighting was New England with 25%. LIMITATIONS: This survey only reflects the field of dermatology and beliefs/policies of program directors. CONCLUSION: This survey highlighted that training programs allowing moonlighting tend to have a more positive outlook on the practice than programs who do not. Results revealed trends that suggest that states in regions with less access to dermatologic care were more inclined to allow moonlighting.

Imaging of Mohs micrographic surgery sections using full-field optical coherence tomography: a pilot study.

BACKGROUND: Full-field optical coherence tomography (FF-OCT) is a new noninvasive imaging technique that can see down to the cellular level without tissue preparation or contrast agents. OBJECTIVE: To use FF-OCT to image Mohs micrographic surgery specimens and verify the ability of a dermatopathologist to identify or exclude malignancy. MATERIALS AND METHODS: Two Mohs surgeons supplied 18 Mohs sections from 11 patients. Each section was scanned using the FF-OCT, and a dermatopathologist blinded to the diagnosis examined the images for malignancy. The FF-OCT images were then compared with the intraoperative hematoxylin and eosin (H&E)-stained frozen sections for concordance. RESULTS: All 9 FF-OCT images interpreted as negative for malignancy were in agreement with the H&E frozen sections. Six of the remaining FF-OCT images were correctly interpreted as positive for malignancy, and three were deferred because malignancy could not be confirmed or excluded. CONCLUSION: Malignancy in Mohs sections can correctly be identified or excluded using FF-OCT. Although not ready for clinical use in its current state, FF-OCT has the potential to be incorporated into the Mohs workflow in the future.

A 7-week-old Nepali girl with a perianal ulcer: brief report.

Cytomegalovirus (CMV) can rarely present with skin findings. Cutaneous CMV is most often found in patients who are immunocompromised because of acquired immunodeficiency syndrome, lymphoma, or other conditions. We present a rare case of an immunocompetent 7-week-old girl with a perianal ulcer attributed to CMV.

To debrief or not to debrief our heroes: that is the question.

Psychological debriefing was developed in the 1980s as an approach for use with people whose work exposes them to stressful incidents. It aims to help them to process the thoughts and emotions arising from their work. Subsequently, several randomized controlled trials tested truncated forms of debriefing in a different population: primary victims of unexpected trauma. These trials, and particularly two in which debriefing appeared to be harmful, led two major reviews to warn practitioners not to offer debriefing. Consequently, many organizations have stopped providing debriefing to employees who face trauma in their routine work. This paper argues that there are at least three reasons for the apparent failure of 'debriefing' in the two studies that reported adverse effects. First, the 'debriefing' did not follow protocol in terms of timing, length, and training and independence of the debriefer. Second, the patients who were 'debriefed' reported more severe initial symptoms than those who were not. Third, 'debriefing' was used with individuals for whom it was not originally intended. Psychological debriefing is intended to be used with groups of people who have been briefed together before going on to work together in stressful situations. Such groups have reported that they find psychological debriefing helpful, and research is emerging indicating that appropriate debriefing may indeed benefit these groups. We call for reviewers to recognize the limitations of debriefing research and not to overgeneralize their conclusions.

ALK mutants in the kinase domain exhibit altered kinase activity and differential sensitivity to small molecule ALK inhibitors.

Abnormal expression of constitutively active anaplastic lymphoma kinase (ALK) chimeric proteins in the pathogenesis of anaplastic large-cell lymphoma (ALCL) is well established. Recent studies with small molecule kinase inhibitors have provided solid proof-of-concept validation that inhibition of ALK is sufficient to attenuate the growth and proliferation of ALK (+) ALCL cells. In this study, several missense mutants of ALK in the phosphate anchor and gatekeeper regions were generated and their kinase activity was measured. NPM-ALK L182M, L182V, and L256M mutants displayed kinase activity in cells comparable to or higher than that of NPM-ALK wild type (WT) and rendered BaF3 cells into IL-3-independent growth, while NPM-ALK L182R, L256R, L256V, L256P, and L256Q displayed much weaker or little kinase activity in cells. Similar kinase activities were obtained with corresponding GST-ALK mutants with in vitro kinase assays. With regard to inhibitor response, NPM-ALK L182M and L182V exhibited sensitivity to a fused pyrrolocarbazole (FP)-derived ALK inhibitor comparable to that of NPM-ALK WT but were dramatically less sensitive to a diaminopyrimidine (DAP)-derived ALK inhibitor. On the other hand, NPM-ALK L256M exhibited >30-fold lower sensitivity to both FP-derived and DAP-derived ALK inhibitors. The growth inhibition and cytotoxicity of BaF3/NPM-ALK mutant cells induced by ALK inhibitors were consistent with inhibition of cellular NPM-ALK autophosphorylation. In a mouse survival model, treatment with the orally bioavailable DAP-ALK inhibitor substantially extended the survival of the mice inoculated with BaF3/NPM-ALK WT cells but not those inoculated with BaF3/NPM-ALK L256M cells. Binding of ALK inhibitors to ALK WT and mutants was analyzed using ALK homology models. In summary, several potential active ALK mutants were identified, and our data indicate that some of these mutants are resistant to select small molecule ALK inhibitors. Further characterization of these mutants may help to identify and develop potent ALK inhibitors active against both WT and resistant mutants of ALK.