Leukemia Cutis in Relapsed Acute Myeloid Leukemia: A Call for Distinct Classification.

BACKGROUND Acute myeloid leukemia is characterized by dysregulated proliferation and maturation arrest of myeloid precursors, precipitating a spectrum of complications. Among these, leukemia cutis refers specifically to ectopic deposition and proliferation of malignant myeloid cells within the skin. This infiltration pathogenesis remains unclear. Although there are numerous reports of leukemia cutis in the setting of acute myeloid leukemia or primary acute myeloid leukemia, there are no specific reports of leukemia cutis in the setting of relapsed acute myeloid leukemia. CASE REPORT A 59-year-old woman, with a history of remission from poor-risk acute myeloid leukemia, previously treated with chemotherapy and allogenic bone marrow transplant, presented with shortness of breath, lethargy, anemia, thrombocytopenia, and subcutaneous nodules on lower extremities. Leukemia cutis was diagnosed, in the setting of relapsed acute myeloid leukemia. After unsuccessful salvage chemotherapy and being deemed unsuitable for further treatment, she pursued palliative care and died a month later. CONCLUSIONS Our case highlights a lack of reporting or making a distinction of those patients with relapsed acute myeloid leukemia and leukemia cutis. Consequently, it can be deduced that patients who simultaneously have relapsed acute myeloid leukemia and leukemia cutis are expected to fare worse in terms of clinical outcomes than those with primary acute myeloid leukemia and leukemia cutis. Relapsed acute myeloid leukemia patients with leukemia cutis should be classified as a distinct group, warranting further research into aggressive therapeutic targets and survival rates, while emphasizing the need for more vigilant follow-up and lower biopsy thresholds for cutaneous lesions in patients with treated hematologic malignancies.

Atypical Fibroxanthoma Treated with a Topical Combination of Imiquimod, Tazarotene, and 5-Fluorouracil.

This case report describes an 80-year-old man who presented with a growing erythematous nodule with erosion, measuring 0.6 cm × 0.6 cm, on his right temple. This lesion was later diagnosed as atypical fibroxanthoma (AFX). Instead of undergoing Mohs surgery, the gold standard treatment, the patient opted to pursue a topical treatment regimen because of financial costs associated with surgical removal and repair. This topical regimen consisted of tazarotene cream, imiquimod cream, and 5-fluorouracil solution, applied for 30 days. The patient was directed to use this combination 5 days per week for 6 weeks. The specified dosage for each medication was a fifth of a packet of imiquimod 5% cream, an equivalent amount of tazarotene 0.1% cream, and a single drop of 5-fluorouracil 2% solution. These were combined on a bandage and placed on the lesion overnight. Following the treatment, a 3-week post-application examination revealed an erosion, 1.0 cm × 0.9 cm, amidst erythema. A subsequent incisional biopsy with histopathology and stains for CD10 and CD99, 3 weeks after treatment, and three punch biopsies with histopathology and stains for CD10 and CD99, 1-year post-treatment, confirmed the absence of AFX. AFX is a superficial variant of pleomorphic dermal sarcoma (PDS), which shares histologic similarities, yet the exact relationship between AFX/PDS and undifferentiated pleomorphic sarcoma is still not well understood. Previous studies have indicated a genomic similarity between AFX/PDS and cutaneous squamous cell carcinoma (cSCC), which suggests the potential efficacy of cSCC-targeted treatments for AFX/PDS. This case marks the first recorded instance of successful topical medical treatment of AFX, offering an alternative for patients who may opt out of surgical intervention. Continued research to assess the broader efficacy of this approach is encouraged.

Urticaria Pigmentosa Without Pruritus.

Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa, which presents with mastocytomas that can cause hives and, when irritated, pruritus. To our knowledge, we are describing the first case of urticaria pigmentosa without pruritus. The patient had a positive Darier's sign, stated that they never felt itchy, and denied ever using a topical steroid or antihistamine. Although our patient declined additional testing, patients like this may benefit from a detailed evaluation of their sensory system through both quantitative sensory testing and genetic analysis. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7558e.

A case of markedly impaired wound repair with angiostatic pazopanib in a patient who had Mohs surgery for a basal cell carcinoma.

This case report highlights the adverse effects of pazopanib, a vascular endothelial growth factor receptor inhibitor, on wound healing after Mohs surgery. A 79-year-old male with metastatic renal cell carcinoma of the lung, on 600 mg daily pazopanib, underwent Mohs surgery for a nodular basal cell carcinoma on his right leg. Despite multiple wound care strategies, his wound deteriorated over 4 months. Discontinuing pazopanib resulted in rapid wound closure within 2 months. However, metastatic lung nodules grew, prompting treatment with immune checkpoint inhibitors, nivolumab, and ipilimumab, which were discontinued due to complications. Near-complete wound healing was observed prior to reintroducing pazopanib (6 months after initial discontinuation), which again led to wound deterioration. Pazopanib negatively impacts wound repair by inhibiting cell proliferation and angiogenesis. Depending on the malignancy or tumor, cessation of pazopanib, or switching to a course of immune checkpoint inhibitors may be warranted perioperatively.

Role of radiotherapy and its contribution to immunotherapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major contributor to cancer-related deaths, with the incidence of HCC increasing in regions of the world with a high incidence of hepatitis B and C. The therapeutic landscape for HCC management has substantially transformed over recent years, shifting towards a multimodal treatment paradigm. This approach provides a range of medical and surgical interventions aimed at managing the disease effectively. Radiotherapy (RT) has surfaced as a critical player in the preoperative management of inoperable HCC, demonstrating potential in downstaging the disease and achieving disease stability. This advantage may potentially be attributed to the abscopal effect, where localized radiation leads to the regression of metastatic cancer outside of the irradiated site through upregulation of the immune system. The advent of recent technological breakthroughs has paved the way for innovative approaches, notably the integration of immunotherapy and RT. This strategy is emerging as a promising avenue for managing HCC. Preliminary findings from the fusion of RT and immunotherapy are encouraging, with ongoing trials keenly evaluating the optimal parameters for therapy administration, such as timing, dosage, and sequence. The development of combined treatments involving immune checkpoint inhibitors (ICIs) has opened new avenues for advanced HCC treatment. Several immunotherapeutic agents with RT are concurrently being explored for their potential contributions to HCC management.

Keratinocyte Carcinoma Chemoprevention With a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

BACKGROUND: The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs. METHODS: We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention. RESULTS: Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P<0.001). CONCLUSIONS: A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.

Geographic Trends in General Surgery Resident Compensation Across the United States.

OBJECTIVE: To examine the effect of cost of living on general surgery resident salaries and identify factors associated with greater incomes and availability of housing stipends. DESIGN: Retrospective cross-sectional analysis of Fellowship and Residency Electronic Interactive Database (FREIDA), institutional websites, and Doximity. Program characteristics were compared through Kruskal-Wallis tests, ANOVA, and χ2 tests. Multivariable linear mixed modeling and multivariable logistic regression were utilized to determine factors associated with higher salary and availability of housing stipend, respectively. SETTING: Three-hundred fifty-one general surgery residency programs in the United States. PARTICIPANTS: Three-hundred-seven general surgery residency programs with available salary data for the 2022 to 2023 academic year. RESULTS: The average postgraduate year 1 resident annual salary was $59,906.00 (standard deviation [SD] ± $5051.97). After adjustment for the cost of living, the average annual income surplus was $22,428.42 (SD ± $4848.64). Cost of living and resident remuneration varied substantially across regions (p < 0.001). Annual income surplus was the highest for programs in the Northeast when compared to other regions (p < 0.001). Resident annual income increased by $510 (95% confidence interval [CI] $430-$590) for each $1000 increase in the cost of living and $150 (95% CI $80-$210) for each 10-rank increase in Doximity general surgery program reputation ranking. An increased cost of living was associated with a higher likelihood of housing stipend availability (odds ratio 1.17, 95% CI 1.07-1.28). CONCLUSIONS: General surgery residents are inadequately compensated for the cost of living, indicating the potential for increased compensation to alleviate economic strain of surgical trainees. As financial stress can have implications for mental and physical well-being, further discussion of current resident salaries and benefits is warranted.

Sun-protective behaviors and sunburn among US adults.

Individuals can reduce the risk of developing skin cancer by minimizing ultraviolet sunlight exposure, though recent trends in sun-protective behaviors remain to be investigated. To evaluate sun-protective behaviors and sunburn among US adults. We analyzed data from the 2010, 2015, and 2020 National Health Interview Survey (NHIS), an annual, cross-sectional survey conducted by the US Census Bureau. Multivariable regression models were stratified by demographic variables and constructed to evaluate sun-protective behaviors and sunburn avoidance across time. From 2010 through 2020, US adults had significantly increased prevalence of seeking shade (p value, 0.003), wearing wide-brimmed hats (< 0.001), wearing long-sleeved shirts (< 0.001), using sunscreen (< 0.001), and avoiding sunburns (< 0.001) and significantly decreased prevalence of sun avoidance (< 0.001). Disparities in sun-protective behaviors also exist among different sexes, ages, education levels, and those reporting higher sun sensitivity. This cross-sectional study found that by 2020, US adults had an increased prevalence of wearing sun-protective clothing and sunscreen use, though decreased prevalence of sun avoidance. Although certain sun-protective behaviors have become more prevalent, the incidence of skin cancer continues to rise. Efforts to understand drivers of sun-protective behaviors and targeted intervention efforts are needed.

Contact Dermatitis in the Surgical Patient: A Focus on Wound Closure Materials.

Irritant and allergic contact dermatitis from wound closure materials can occur in patients after surgical procedures. The resulting inflammation from contact dermatitis can compromise wound healing, mimic surgical site infections, and result in wound dehiscence. Components of wound closure material, such as antibiotic coatings, dyes, sterilizing compounds, or the material itself, have been implicated as contact allergens. This article provides the latest overview of the components of 3 major forms of wound closure materials-sutures, staples, and tissue adhesives-associated with contact dermatitis, discusses their cross-reactivity, and provides diagnostic and treatment guidelines.

Eosinophil-rich linear IgA bullous dermatosis induced by mRNA COVID-19 booster vaccine.

We present a case of eosinophil-rich linear IgA bullous disease (LABD) following the administration of a messenger RNA COVID-19 booster vaccine. A 66-year-old man presented to the emergency department with a 3-week history of a pruritic blistering rash characterized by fluid-filled bullae and multiple annular and polycyclic plaques. He was initially diagnosed with bullous pemphigoid based on a biopsy showing a subepidermal blister with numerous eosinophils. However, direct immunofluorescence studies showed linear IgA and IgM deposition along the basement membrane zone with no immunoreactivity for C3 or IgG. Additionally, indirect immunofluorescence was positive for IgA basement membrane zone antibody. The patient was subsequently diagnosed with LABD and initiated on dapsone therapy with resolution of his lesions at 3-month follow-up. This case illustrates the growing number of autoimmune blistering adverse cutaneous reactions from vaccination. Dermatopathologists should be aware that features of autoimmune blistering diseases can overlap and may not be distinguishable based on these histopathological findings alone. Confirmation with direct immunofluorescence and/or serological studies may be necessary for accurate diagnosis.

Keratinocyte Carcinomas in Immunocompromised Patients Are Reduced After Administration of the Nonavalent Human Papillomavirus Vaccine.

Immunosuppression, as seen in solid organ transplant recipients, is highly associated with the development of keratinocyte carcinomas (KCs). Reducing the level of immunosuppression lowers the incidence of KCs but at the cost of increased potential morbidity and mortality. Recent studies have revealed a greater prevalence of HPV DNA, especially that of β-HPV, in KCs of immunocompromised patients compared to KCs of immunocompetent individuals. A prior report demonstrated that the HPV vaccine was associated with reducing KC incidence in immunocompetent patients. The nonavalent HPV vaccine was administered to two immunosuppressed individuals with histories of multiple prior KCs. Both patients are male, with Patient 1 being a liver transplant recipient who was on tacrolimus for an extended period and Patient 2 having Crohn’s disease and currently being treated with mercaptopurine. The treatment was well tolerated without adverse events and was associated with dramatic reductions in average incidence of KCs/year in both patients. Patient 1 demonstrated an 88% reduction in new KCs/year (87% squamous cell carcinomas (SCCs); 100% basal cell carcinomas (BCCs) post-injection of the intramuscular vaccine and Patient 2 demonstrated a 63% reduction in incidence of KCs/year (30% SCCs; 100% BCCs). Evidence links the β-HPV genera to the development of SCCs and actinic keratoses. The nonavalent HPV vaccine, containing antigens of the α-HPV genera, may also induce humoral immunity to β-HPV due to shared expression of L1 and L2 capsid proteins. The HPV vaccine may be an effective tool in the prevention of KCs in immunosuppressed patients. J Drugs Dermatol. 2022;21(5):526-528. doi:10.36849/JDD.6536.

Atypical Presentation of Transcranial Extension of Intracranial Meningiomas.

ABSTRACT: Meningiomas are the most common primary central nervous system tumors. These tumors predominantly arise from the neural crest-derived meningothelial cells of the arachnoid dural layer. Intracranial meningiomas are stratified with the World Health Organization classification of tumors. Cutaneous meningiomas present rarely and have their own criteria classification (Lopez classification) of 3 types. The first type is congenital. The second consists of ectopic soft-tissue meningiomas. The third involves tumors that extended into the dermis or subcutis that include the neuroaxis. We present a case of a 56-year-old woman with 4 facial tumors that clinically seemed to be cutaneous cysts or lipomas. She reported a history of surgical resection of an intracranial meningioma on the left forehead scalp line 15 years ago. A recent surgical resection of a glabellar tumor revealed a glistening white mass. Pathologic examination revealed a poorly circumscribed mass in the deep dermis and subcutaneous area with sheets of epithelioid and plasmacytoid tumor cells with nuclear pleomorphism. Mitotic figures and necrosis were also evident. Immunohistochemistry revealed positivity for epithelial membrane antigen, p63, and ERG. The tissue had negative staining for p40, CK7, SOX10, CD68, SMA, desmin, and CD34. The patient's medical history was remarkable in that these tumors had only been growing for several months. Brain magnetic resonance imaging demonstrated widespread tumors in bilateral frontal lobes, skull, orbits, and sinuses. Considering the transcranial extensions and 15-year recurrence time, she was diagnosed with a recurrent atypical brain meningioma type II and cutaneous meningioma Lopez type III.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

Treating Melanoma in Situ During a Pandemic with Telemedicine and a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

The recent coronavirus disease 2019 (COVID-19) pandemic has created a quandary for the physician in terms of evaluating and treating cutaneous skin cancers, particularly melanomas. At the onset of the pandemic, many planned medical and surgical visits for skin cancers were postponed. Physicians and patients have had to balance the risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with that of worsening morbidity and mortality due to delays in skin cancer treatments. We present a male patient who had two melanoma-in-situs (MISs) that were treated during the COVID-19 pandemic with a combination of topical imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream. The successful treatments occurred without in-person visits and with the aid of telemedicine. Although surgery is the standard for the treatment of melanoma in situ, this case demonstrates an effective viable treatment modality for MIS during a pandemic situation.