Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease. Pediatric BPDCN is believed to be clinically less aggressive but often with more dissemination at presentation than adult cases. Unlike adults who almost always proceed to a hematopoietic stem cell transplantation in first complete remission if transplant-eligible, the majority of children can be cured with a high-risk acute lymphoblastic leukemia-like regimen. Hematopoietic stem cell transplantation is recommended for children with high-risk disease, the definition of which continues to evolve, or those in relapse and refractory settings where outcomes continue to be dismal. Novel agents used in other hematologic malignancies and CD123 targeted agents, including chimeric antigen receptor T-cells and monoclonal/bispecific antibodies, are being brought into research and practice. Our goal is to provide a comprehensive review of presentation, diagnosis, and treatment by review of pediatric cases reported for the last 20 years, and a review of novel targeted therapies and therapies under investigation for adult and pediatric patients.

Cutaneous T-Cell Lymphoma: Current and Emerging Therapies.

Cutaneous T-cell lymphomas (CTCLs) are clinically heterogeneous T-cell lymphomas that arise in the skin and are characterized by their clinical and pathological features. This review will focus on mycosis fungoides (MF) and Sézary syndrome (SS), which represent 60% to 80% and less than 10% of CTCL cases, respectively. While most patients with MF present with patches and plaques and can be successfully treated with skin-directed therapies, a minority of patients progress from early to advanced stages or undergo large cell transformation. SS is defined as erythroderma, lymphadenopathy, and more than 1000 circulating atypical T-cells/uL with cerebriform nuclei. It has a poor overall survival of 2.5 years. Given the overall rarity of CTCLs, it is notable that clinical trials of treatments for MF/SS have been successfully completed, resulting in FDA approvals of novel therapies with increasing overall response rates. This review outlines the current multidisciplinary approach to diagnosing and treating MF/SS, with a focus on combining skin-directed therapies with emerging targeted and investigational systemic therapies. Integrating these anticancer therapies with skin care and bacterial decolonization is critical for comprehensive management. Curing patients with MF/SS may be possible by using a personalized medicine approach including novel combination strategies, restoration of T helper 1 cytokines, and avoidance of immunosuppressive regimens.

Pityriasis Rubra Pilaris After Moderna COVID-19 Vaccination: A Case Report and Literature Review.

ABSTRACT: To date, over 60% of the world's population has received at least 1 dose of coronavirus disease 2019 (COVID-19) vaccination, with over 12 billion doses administered globally. Commonly reported adverse effects of COVID-19 vaccination include fever, headache, myalgia, and injection site reactions. The spectrum of documented cutaneous reactions after COVID-19 vaccination is broad; however, pityriasis rubra pilaris (PRP) or PRP-like eruption secondary to COVID-19 vaccine is exceedingly rare, with only 17 cases previously reported to date in the English literature. In this article, we describe an additional case of COVID-19 vaccination-associated PRP in a 50-year-old woman with a history of metastatic breast carcinoma, who developed a widespread cutaneous eruption characteristic of PRP, including palmoplantar keratoderma, 10 days after her third dose of Moderna COVID-19 vaccine. Punch biopsy specimen showed epidermal hyperplasia with overlying hyperkeratosis, alternating orthokeratosis and parakeratosis and focal follicular plugging, supporting the diagnosis of PRP. The patient improved within weeks of initiating oral acitretin and topical steroids, with resolution achieved after 3 months of continued therapy. To the best of our knowledge, this is the third reported case of Moderna COVID-19 vaccination-associated PRP and collectively the 18 th after the administration of all COVID-19 vaccines currently available, including Pfizer-BioNTech, and AstraZeneca.

Condyloma and coincidental epidermodysplasia verruciformis acanthoma positive for human papillomavirus-14 and -21.

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes individuals to persistent infection with ß-human papillomavirus (HPV) genotypes. The term EDV acanthoma may be applied to lesions with incidental findings of EDV-defining histopathological features without clinical signs of EDV. We report a case of HPV-14- and -21-positive EDV acanthoma arising in association with condyloma in a female patient with a history of low-grade squamous intraepithelial lesion of the cervix positive for high-risk HPV (non-16/18), chronic kidney disease, and systemic lupus erythematosus. The patient had no family or personal history of EDV, but the patient was on immunosuppressive therapy with mycophenolate mofetil and prednisone. A biopsy specimen from one of the perianal lesions revealed histopathologic changes consistent with EDV in the setting of condyloma. Molecular testing showed HPV-14 and -21, which supported the coexistence of condyloma with EDV acanthoma.

Vitiligo-like manifestations of graft-versus-host disease in a pediatric population.

Vitiligo-like changes are an uncommon cutaneous manifestation of graft-versus-host disease (GVHD). We report three cases and review the literature of pediatric patients with vitiligo-like changes associated with GVHD. Improved characterization of this phenomenon may lend insight into the biologic pathways that underlie both vitiligo and GVHD.

Phase I Study of Stereotactic Body Radiotherapy plus Nivolumab and Urelumab or Cabiralizumab in Advanced Solid Tumors.

PURPOSE: CD137 agonism and CSF1R blockade augment stereotactic body radiotherapy (SBRT) and anti-programmed death-1 in preclinical models. We evaluated the safety and efficacy of SBRT with nivolumab+urelumab (CD137 agonist) or nivolumab+cabiralizumab (CSF1R inhibitor). PATIENTS AND METHODS: This phase I clinical trial enrolled patients with advanced solid tumors that had progressed on standard therapies. SBRT was delivered to 1-4 metastases with nivolumab+urelumab or nivolumab+cabiralizumab given concurrently and following SBRT. Dose-limiting toxicity (DLT) was the primary endpoint with anatomic location-specific SBRT doses deemed safe if ≤33% DLT frequency was observed. Secondary endpoints included RECISTv1.1 response, progression-free survival (PFS), overall survival (OS), and molecular correlative studies. RESULTS: Sixty patients were enrolled, and median follow-up for living patients is 13.8 months. Of these, 23 (38%) received SBRT+nivolumab+urelumab and 37 (62%) received SBRT+nivolumab+cabiralizumab. Seven patients (12%) experienced a DLT (n = 3 grade 3, n = 4 grade 4) in the following anatomic cohorts: abdominal/pelvic (3/17, 18%), liver (1/13, 8%), central lung (2/14, 14%), and peripheral lung (1/12, 8%). Of 41 patients radiographically evaluable for best overall response including 55 radiated and 23 unirradiated RECIST target lesions, 2 had complete responses (5%), 7 had partial responses (17%), 12 had stable disease (29%), and 20 had progression (49%). Median estimated PFS and OS are 3.0 months [95% confidence interval (CI), 2.9-4.8] and 17.0 months (95% CI, 6.8-undetermined), respectively. No patients with elevated pre-SBRT serum IL8 experienced a response. CONCLUSIONS: SBRT to ≤4 sites with nivolumab+urelumab or nivolumab+cabiralizumab for treating advanced solid tumors is feasible with acceptable toxicity and modest antitumor activity.See related commentary by Rodriguez-Ruiz et al., p. 5443.

Role of imaging in low-grade cutaneous B-cell lymphoma presenting in the skin.

BACKGROUND: Whole-body imaging is the current standard of care for staging all patients presenting with skin lesions of B-cell lymphomas (BCLs), regardless of skin disease extent; however, supporting data are lacking. OBJECTIVE: To determine the clinical utility of imaging in the detection of systemic involvement in low-grade cutaneous BCLs in the skin. METHODS: Retrospective cohort analysis of patients presenting with cutaneous lesions of BCLs at Memorial Sloan Kettering Cancer Center and Stanford University during 1997-2016. RESULTS: At initial staging, of the 522 patients, extracutaneous disease was noted in 3.6% and 8.8% of patients with marginal zone lymphoma (MZL, n = 306) and follicle center lymphoma (FCL, n = 216) histology, respectively. In patients with systemic involvement, imaging alone identified 81.8% (9/11) of MZL cases and 89.4% of follicular lymphoma cases. In primary cutaneous MZL, 1.7% of patients subsequently had extracutaneous involvement (median follow-up 45 months), and in primary cutaneous FCL. 3.0% subsequently had extracutaneous involvement (median follow-up 47 months). LIMITATIONS: This was a retrospective study. CONCLUSION: Imaging is effective at identifying patients with systemic involvement in indolent BCLs present in the skin; however, incidence is low. After negative initial staging, primary cutaneous MZL patients may be followed clinically without routine imaging.

Prospective Cohort Study Investigating Changes in Body Image, Quality of Life, and Self-Esteem Following Minimally Invasive Cosmetic Procedures.

BACKGROUND: Minimally invasive cosmetic injectable procedures are increasingly common. However, a few studies have investigated changes in psychosocial functioning following these treatments. OBJECTIVE: To assess changes in body image, quality of life, and self-esteem following cosmetic injectable treatment with soft tissue fillers and neuromodulators. METHODS: Open, prospective study of 75 patients undergoing cosmetic injectable procedures for facial aging to evaluate changes in psychosocial functioning within 6 weeks of treatment. Outcome measures included the Derriford appearance scale (DAS-24), body image quality of life inventory (BIQLI), and the Rosenberg self-esteem scale. RESULTS: Body image dissatisfaction, as assessed by the DAS-24, improved significantly 6 weeks after the treatment. Body image quality of life, as assessed by the BIQLI, improved, but the change did not reach statistical significance. Self-esteem was unchanged after the treatment. CONCLUSION: Minimally invasive cosmetic injectable procedures were associated with reductions in body image dissatisfaction. Future research, using recently developed cosmetic surgery-specific instruments, may provide further insight into the psychosocial benefits of minimally invasive procedures.

Pigmentary changes in patients treated with targeted anticancer agents: A systematic review and meta-analysis.

BACKGROUND: The discovery of signaling networks that drive oncogenic processes has led to the development of targeted anticancer agents. The burden of pigmentary adverse events from these drugs is unknown. OBJECTIVE: To conduct a systematic review and meta-analysis of published clinical trials and determine the incidence and risk of development of targeted therapy-induced pigmentary changes. METHODS: A comprehensive search was conducted to identify studies reporting targeted therapy-induced pigmentary changes. The incidence and relative risk were calculated. Case reports and series were reviewed to understand clinical characteristics. RESULTS: A total of 8052 patients from 36 clinical trials were included. The calculated overall incidences of targeted cancer therapy-induced all-grade pigmentary changes in the skin and hair were 17.7% (95% confidence interval [CI], 11.9-25.4) and 21.5% (95% CI, 14.9-30.1), respectively. The relative risk of all-grade pigmentary changes of skin and hair were 93.7 (95% CI, 5.86-1497.164) and 20.1 (95% CI, 8.35-48.248). Across 53 case reports/series (N = 75 patients), epidermal growth factor receptor and breakpoint cluster region-abelson inhibitors were the most common offending agents. LIMITATIONS: Potential under-reporting and variability in oncologists reporting these events. CONCLUSION: There is a significant risk of development of pigmentary changes during treatment with targeted anticancer therapies. Appropriate counseling and management are critical to minimize psychosocial impairment and deterioration in quality of life.

Development of RET mutant cutaneous angiosarcoma during BRAF inhibitor therapy.

Treatment with BRAF inhibitors may lead to paradoxical mitogen-activated protein kinase (MAPK) pathway activation and accelerated tumorigenesis in cells with preexisting oncogenic hits. This phenomenon manifests clinically in the development of squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) in patients treated with BRAF inhibitors. Cases of extracutaneous malignancies associated with BRAF inhibitors have also been reported. We present a case of a patient who developed a cutaneous angiosarcoma 6 months after initiation of vemurafenib therapy. Next-generation sequencing (NGS) revealed a mutation in RET, which lies upstream of the MAPK pathway. This case highlights that treatment with BRAF inhibitors may promote the accelerated growth of secondary malignancies. Physician awareness of the spectrum of secondary malignancies associated with BRAF inhibitor treatment will support their early detection and treatment.

Assessing Surgical Training and Deliberate Practice Methods in Dermatology Residency: A Survey of Dermatology Program Directors.

BACKGROUND: Resident surgical education and technical skills may be enhanced with deliberate practice-based learning. Deliberate practice methods, such as simulation-based training and formal skills-based assessments, allow for trainees to repeatedly practice a defined task with expert supervision and feedback. OBJECTIVE: The authors sought to characterize how surgical skills are taught and assessed in dermatology residency, with an emphasis on whether deliberate practice methods are incorporated in the surgical curriculum. MATERIALS AND METHODS: A survey was administered to program directors at 117 Accreditation Council for Graduate Medical Education-approved dermatology residency programs during 2013 to 2014. RESULTS: A total of 42 responses (36%) were collected. Over half of programs (57%) devote 10 to 30 hours each year to surgical didactics. Sixty-nine percent of programs use simulation models, and 62% of programs use formal assessment-guided feedback in evaluating surgical skills. Residents most commonly assume the role of primary surgeon in excisional surgery (100%) and less commonly in graft and flap reconstruction (52% and 52%, respectively). Twenty-nine percent of residents are the primary surgeons in Mohs micrographic surgery. CONCLUSION: Dermatology residency programs are incorporating deliberate practice-based tenets in the surgical curriculum. These results provide a benchmark for programs to assess and improve the quality of dermatologic surgery training.

Histopathologic and mutational analysis of a case of blue nevus-like melanoma.

Blue nevi are a heterogeneous group of dermal melanocytic proliferations that share a common clinical appearance but remain controversial in their histopathologic and biologic distinction. While common blue nevi and cellular blue nevi are well-defined entities that are classified without significant controversy, the distinction between atypical cellular blue nevi and blue nevus-like melanoma remains diagnostically challenging. We report a case of a 46-year-old female with recurrent blue nevus-like melanoma of the scalp with liver metastases; mutational analysis showed GNA11 Q209L and BAP1 Q393 mutations. To our knowledge, this is the first case of blue nevus-like melanoma with GNA11 and BAP1 mutations. These particular mutations and the predilection for liver metastases in our patient's case underscore a fundamental biological relationship between blue nevi and uveal melanoma and suggest the two entities may prove amenable to similar diagnostic and prognostic testing and targeted therapies.

Motivations for seeking minimally invasive cosmetic procedures in an academic outpatient setting.

BACKGROUND: The demand for minimally invasive cosmetic procedures has continued to rise, yet few studies have examined this patient population. OBJECTIVES: This study sought to define the demographics, social characteristics, and motivations of patients seeking minimally invasive facial cosmetic procedures. METHODS: A prospective, single-institution cohort study of 72 patients was conducted from 2011 through 2014 at an urban academic medical center. Patients were aged 25 through 70 years; presented for botulinum toxin or soft tissue filler injections; and completed demographic, informational, and psychometric questionnaires before treatment. Descriptive statistics were conducted using Stata statistical software. RESULTS: The average patient was 47.8 years old, was married, had children, was employed, possessed a college or advanced degree, and reported an above-average income. Most patients felt that the first signs of aging occurred around their eyes (74.6%), and a similar percentage expressed this area was the site most desired for rejuvenation. Almost one-third of patients experienced a "major life event" within the preceding year, nearly half had sought prior counseling from a mental health specialist, and 23.6% were being actively prescribed psychiatric medication at the time of treatment. CONCLUSIONS: Patients undergoing injectable aesthetic treatments in an urban outpatient academic center were mostly employed, highly educated, affluent women who believed that their procedure would positively impact their appearance. A significant minority experienced a major life event within the past year, which an astute clinician should address during the initial patient consultation. This study helps to better understand the psychosocial factors characterizing this patient population. LEVEL OF EVIDENCE: 4 Therapeutic.

Achromobacter xylosoxidans Bacteremia and Cellulitis: A Report of a Case.

Achromobacter xylosoxidans is a rare, opportunistic infection most commonly encountered in immunocompromised patients during hospitalization. Primary uncomplicated bacteremia, catheter-associated infections, and pneumonia have been reported as the most common clinical presentations; skin and soft tissue infections from A. xylosoxidans are rare. We describe a case of A. xylosoxidans presenting as cellulitis and bacteremia in an immunocompromised patient.

Striking follicular eruption to pegylated liposomal doxorubicin.

The adverse effects of pegylated liposomal doxorubicin are primarily cutaneous. The majority of these cutaneous side effects manifest as palmar-plantar erythrodysesthesia, whereas few reports of other cutaneous reactions exist in the literature. The authors report a case of an exuberant follicular eruption in a patient treated with pegylated liposomal doxorubicin. This case also highlights the potential mechanism underlying this unusual histological and clinical reaction.