Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

A Histopathologic Scoring System for Perineural Invasion Correlates With Adverse Outcomes in Patients With Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Perineural invasion (PNI) is a known risk factor for recurrence, metastasis, and death in cutaneous squamous cell carcinoma (cSCC). Current staging systems include PNI, but none define its extent or severity. OBJECTIVE: To identify histopathologic features of cSCC with PNI that may be associated with adverse outcomes. MATERIALS AND METHODS: This is a retrospective cohort study that included 45 patients with cSCC and PNI treated with surgical excision. Histopathologic slides were analyzed for 5 features of PNI: largest affected nerve diameter, number of nerves affected, depth of nerve involvement, intra- versus extratumoral PNI, and focal versus circumferential PNI. RESULTS: The median largest affected nerve diameter was 0.13 mm, and the median number of nerve structures involved was 4. After a median follow-up time of 24 months, 6 patients developed adverse outcomes, including 2 local recurrences, 4 metastases, and 2 tumor-related deaths. Univariate logistic regression analysis revealed that nerve diameter and number of affected nerves were significantly associated with adverse outcome. A composite PNI score, calculated from 5 histopathologic features, was the strongest predictor of adverse outcome (p = .020). CONCLUSION: Histopathologic features of PNI can be quantified with a composite PNI score that is significantly associated with adverse outcomes in cSCC.

DUSP22-IRF4 rearrangement in AIDS-associated ALK-negative anaplastic large cell lymphoma.

Patients with AIDS have increased risk of developing lymphomas, such as anaplastic large cell lymphoma (ALCL), which generally carry a poor prognosis. The DUSP-IRF4 genetic rearrangement in ALCL confers a favourable prognosis in HIV-negative patients; it is unknown how this interacts clinically with HIV/AIDS. A man aged 53 years presented with subcutaneous nodules on the scalp and axillae, and diffuse lymphadenopathy. Biopsy of subcutaneous nodule and lymph node showed large atypical anaplastic lymphocytes which were CD30+ and anaplastic lymphoma kinase-negative, consistent with primary systemic ALCL. In addition, he was found to be HIV-positive and diagnosed with AIDS. Genetic testing of the tissue revealed a DUSP22-IRF4 rearrangement. Complete remission was achieved with HyperCVAD and subsequent brentuximab vedotin monotherapy. We report a case of AIDS-associated primary systemic ALCL with a DUSP22-IRF4 rearrangement. AIDS-associated ALCL is an aggressive lymphoma, with a poor prognosis. However, the presence of the genetic rearrangement, previously unseen in this disease, drastically altered the disease course. This case highlights the value of genetic testing and identifies DUSP22-IRF4-associated ALCL in the setting of HIV-associated lymphoproliferative disorders.

Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy.

BACKGROUND: Bullous disorders associated with anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy are increasingly reported and may pose distinct therapeutic challenges. Their frequency and impact on cancer therapy are not well established. OBJECTIVE: To evaluate the clinical and histopathologic findings, frequency, and impact on cancer therapy of bullous eruptions due to anti-PD-1/PD-L1 therapy. METHODS: We retrospectively reviewed the medical records of patients evaluated by the oncodermatology clinic and consultative service of Yale New Haven Hospital from 2016 to 2018. RESULTS: We identified 9 of 853 patients who developed bullous eruptions (∼1%) that were treated with an-PD-1/PD-L1 therapy at our institution during the study period: 7 presented with bullous pemphigoid, 1 presented with bullous lichenoid dermatitis, and 1 presented with linear IgA bullous dermatosis in the context of vancomycin therapy. In all, 8 patients required systemic steroids, 5 required maintenance therapy, and 8 required interruption of immunotherapy. All 9 patients had an initial positive tumor response or stable disease, but 4 went on to develop disease progression. LIMITATIONS: This was a retrospective study from a single tertiary care center. CONCLUSIONS: Bullous disorders developed in approximately 1% of patients treated with anti-PD-1/PD-L1 therapy at our institution and frequently resulted in interruption of immune therapy and management with systemic corticosteroids and occasionally steroid-sparing agents.

Emerging concepts and recent advances in basal cell carcinoma.

Basal cell carcinoma (BCC) is the most common malignancy worldwide, arising from non-keratinizing cells within the basal layer of the epidermis. The incidence of BCC continues to rise annually, increasing the burden of management of these carcinomas and the morbidity associated with their treatment. While surgical interventions such as Mohs micrographic surgery and surgical excision are the standard of care and yield the highest cure rates, the number of non-surgical interventions approved for the treatment of BCC continues to expand. We review various surgical and non-surgical approaches to the treatment of BCC, focusing on targeted molecular therapies that are approved for locally advanced or recurrent disease.

The effect of comorbidities on overall mortality in Stevens- Johnson Syndrome: an analysis of the Nationwide Inpatient Sample.

BACKGROUND: Stevens Johnson Syndrome (SJS) is a life threatening skin condition with an overall mortality rate of 5%. Although the causes and pathology of the disease have been well studied, the factors that significantly contribute to mortality remain unclear. OBJECTIVE: To determine relevant risk factors that increase the likelihood of inpatient mortality after diagnosis of SJS. METHODS: A retrospective cohort study of the 2010-2011 Healthcare Costs and Utilization Project (HCUP) Nationwide InpatientSample (NIS) database was conducted. This study included 1,811 patients who encountered inpatient hospital stays with a discharge diagnosis of SJS. RESULTS: The primary outcome of our study was inhospital mortality. We analyzed the prevalence and associated inpatient mortality of underlying critical illness in patients with SJS. Three age ranges of patients in this study showed significantly increased rates of inpatient mortality by odds-ratio with a 95% CI: 70-79 years (10.91% mortality, OR=4.57, p=0.001),80-89 years (10.67% mortality, OR=4.48, p=0.001), and 90+ years (9.30% mortality, OR=4.22, p=0.028). Two comorbid conditions showed significant association with increased inpatient mortality in SJS by odds-ratio with a 95% CI: cirrhosis (14.58% mortality, OR=2.79,p=0.028) and metastatic disease (10.62% mortality,OR=1.87, p=0.031). INTERPRETATION: Age (70+ years), cirrhosis, and metastatic disease were identified as significantly associated with inpatient mortality after diagnosis with SJS. These findings enhance current understanding of the pathology of this disease, as well as help improve clinical management of high-risk patients to reduce inpatient mortality.

Koebnerization of Hailey-Hailey disease into a cutaneous drug eruption of acute generalized exanthematous pustulosis associated with systemic symptoms.

We describe a 65-year-old Caucasian female with well-controlled Hailey-Hailey disease (HHD) who developed acute generalized exanthematous pustulosis (AGEP) with severe systemic symptoms. Despite sparing of the patient's intertriginous skin, histopathologic evidence of HHD was observed in all biopsies, suggestive of a unique koebernization phenomenon of HHD to areas of cutaneous drug eruption. While internal organ involvement is less commonly reported in AGEP, there are an increasing number of patients with signs and symptoms suggestive of an AGEP/drug reaction with eosinophilia and systemic symptoms (DRESS) spectrum of cutaneous drug disorders. Early diagnosis of patients with AGEP and systemic symptoms is critical so that these patients may receive prompt and aggressive systemic therapy to decrease the risk of end organ damage and improve overall morbidity and mortality.

UV-based therapy.

UV phototherapy has a long history of use for the treatment of select diseases in dermatology. Its use has evolved into more effective and targeted modalities, including psoralen + UV-A photochemotherapy, narrowband UV-B, excimer laser, and UV-A1 phototherapy. With its proven record of efficacy and safety, UV phototherapy is an excellent option in the treatment of an ever-growing number of skin conditions.

Histopathology of the inner ear in patients with xeroderma pigmentosum and neurologic degeneration.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations resulting in defective repair of DNA damage. XP patients have a markedly increased risk of ultraviolet-induced neoplasms and premature aging of sun-exposed tissue. Approximately 25% of XP patients in the United States have neurologic abnormalities including progressive sensorineural hearing loss (SNHL). OBJECTIVE: To describe the temporal bone histopathology in 2 individuals with XP (XPA and XPD) with neurologic degeneration and to discuss the possible causes of deafness in these patients. METHODS: Temporal bones were removed at autopsy and studied using light microscopy. RESULTS: In the case with XPD, the organ of Corti was missing throughout the cochlea, whereas the case with XPA demonstrated scattered presence of sensory cells in the middle and apical turns. In both cases, there was moderate-to-severe patchy atrophy of the stria vascularis in all turns, and cochlear neurons were severely atrophied compared with age-matched controls, with loss of both peripheral dendrites and central axons. There was severe degeneration of Scarpa's ganglion in the case with XPA. CONCLUSION: Two cases of XP with neurologic degeneration are reported. The case with XPD demonstrated a more severe audiologic phenotype than XPA, although both had similar findings such as atrophy of the organ of Corti, stria vascularis, and spiral ganglia leading to severe or profound SNHL by the third decade of life. It is not clear if the neuronal degeneration in the inner ear was primary or secondary to loss of neuroepithelial cells.

Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration.

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (>20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average ≥10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system.

Irreversible electroporation in eradication of rabbit VX2 liver tumor.

PURPOSE: To show the effectiveness and safety of irreversible electroporation (IRE) in treating large tumor models. MATERIALS AND METHODS: VX2 liver tumor implantation was performed in 35 New Zealand White Rabbits. The rabbits were divided into three groups 1 week after implantation. The control group included 15 rabbits; the remaining 20 rabbits were divided into two IRE treatment groups. For the treatment groups, 10 rabbits underwent ablation with a single IRE application (IRE-S group), and 10 rabbits underwent ablation with multiple IRE applications (IRE-M group). Treatments and outcomes were analyzed using ultrasound, contrast-enhanced computed tomography (CT), and immunohistologic staining (hematoxylin and eosin [H&E], P-53, Ki-67, CD30, and vascular endothelial growth factor receptor [VEGFR] staining, and terminal deoxynucleotidyl-transferase-mediated 2'-deoxyuridine 5'-triphosphate [dUTP]-biotin nick-end labeling [TUNEL] assay). RESULTS: Multiple IRE ablations consistently produced complete cell death in all the animals in the IRE-M group (n = 10, IRE ablation time 2.45 minutes ± 0.3). The results were validated with ultrasound, CT, H&E, Ki-67, P53, and TUNEL assay. A high level of CD30-positive cells were identified in the IRE groups. A sharply demarcated ablation zone with no damage to surrounding vital structures was observed in all IRE-treated tissues. No complications during or after ablation were observed in any of the animals. CONCLUSIONS: The effects of IRE were shown in a large tumor model with single and multiple IRE ablations (IRE-S and IRE-M treatment groups); complete ablation of the tumor was seen in the IRE-M group. These findings successfully show the beneficial effects and safety of IRE in the treatment of tumors and validate its potential as a clinically translatable treatment.