Primary Cutaneous Malignancies Research Articles

Hippocampal-Sparing Radiation Therapy in Primary Sinonasal and Cutaneous Tumors of the Head and Neck

Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful radiation dose to their hippocampi, but this not a classic avoidance structure in radiation planning. We aimed to characterize the feasibility and tradeoffs of hippocampal-sparing radiation therapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. We retrospectively selected patients who were treated definitively for primary sinonasal or cutaneous malignancies of the H&N at an academic medical center. All received (chemo)radiation alone or adjuvantly and substantial radiation dose to 1 or both hippocampi. We created new HSRT plans for each patient with intensity modulated radiation therapy using the original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines and reviewed by a neuroradiologist. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTVs), and OARs were recorded and compared. There were 18 sinonasal and 12 cutaneous H&N primary tumors (30 patients in total). Median prescription dose was 6600 cGy (range, 5000-7440 cGy), and 14 of the 30 patients received 120 cGy/fraction twice daily, 13 of the 30 patients received 200 cGy/fraction once daily, whereas others received 180-275 cGy/fraction once daily. The relative decrease in ipsilateral hippocampal Dmax and D100% using HSRT was 44% (median, 2009 cGy from 3586 cGy) and 65% (median 434 cGy from 1257 cGy), respectively. There were no statistically significant or clinically meaningful differences in PTV V100%, PTV D1%, or radiation dose to other OARs between HSRT and non-HSRT plans. HSRT is feasible and results in meaningful dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. We suggest target hippocampal constraints of Dmax < 1600 cGy and D100% < 500 cGy when feasible (without compromising PTV coverage or impacting other critical OARs). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Mucocutaneous Manifestations among Patients with Malignancies at a Tertiary Care Center in Maharashtra: A Cross-Sectional Study

Abstract Background: Malignant disorders are a leading cause of mortality and morbidity. Cutaneous manifestations may be presenting features of internal malignancies, leading to diagnosis of occult tumors, while others may occur as adverse reactions to therapeutic modalities. Aims and Objectives: To classify cutaneous manifestations among patients with malignant disorders, document their clinical profile, and analyze them with respect to age, gender, type of malignancy, and treatment. Materials and Methods: One hundred twenty patients with proven malignancy presenting with mucocutaneous lesions were enrolled in the cross-sectional study. On the basis of history, clinical examination, investigations and skin biopsy, the lesions were classified as (1) Primary cutaneous malignancy, (2) Cutaneous metastasis, (3) Paraneoplastic syndromes, (4) Mucocutaneous manifestations not related to malignancies, (5) Adverse effects secondary to treatment modalities. Results: One hundred twenty patients comprised 70 females (58.3%) and 50 males (41.7%). They were categorized as primary cutaneous malignancy (20.2%), hematological malignancies (15%), solid organ malignancy (50.9%), and gastrointestinal malignancies (5%). HIV seropositivity was seen in two patients (1.6%). Maximum belonged to Category 5 (60, 50%), of which 52 (86.7%) were adverse effects of chemotherapy with single patient showing radiation dermatitis and one patient in Category 3 (0.8%). Eleven patients showed cutaneous metastasis (9.1%), predominantly carcinoma breast. Clinically, primary cutaneous malignancies often presented as ulceronodular growths with squamous cell carcinoma being the most common histopathological type (30%). Anagen effluvium was the most common (35%) manifestation overall and in solid organ malignancies followed by melanonychia (16, 13.33%), cutaneous xerosis (9, 7.5%), and mucocutaneous hyperpigmentation (23, 19.16%). Conclusions: Mucocutaneous manifestations need prompt attention to facilitate timely diagnosis and improved outcomes.

Effect of UNO101 on tumor microenvironment in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies.

e14575 Background: Nitric oxide (NO) is a ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes, and NO is implicated in numerous pathological conditions. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO) upregulates innate and adaptive immune cells locally and systemically. Methods: Upon a signed written ICF, a single UNO101 dose of 25,000 parts per million (ppm), administered intratumorally over 5 minutes, was evaluated in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies. Subjects with an ECOG PS of 0–3, at least 3 months of life expectancy and tumor size of 4.5 mm minimum and 30 mm maximum length were eligible for enrollment. RECIST v1.1 and clinical physical examination by PI assessment was utilized to assess the rate of malignant tumor response. Toxicity was graded per NCI CTCAE v5.0. Results: In this first-in-human Phase 1 clinical trial, six subjects, 4F/2M were enrolled with a median age of 61.5 years, (range, 34–81) and ECOG PS reported as 0 or 1. Tumor types enrolled included breast (n=3), melanoma (n=1), and squamous cell carcinoma (n=2) with a median of 4 prior lines of therapy (range, 2–11) and a median of 4.7 years (range, 1.4–9.5) since time of diagnosis to study entry. One related SAE (not dose limiting) of hypoxia, Grade 4, was reported, which resulted in cessation of UNO101 treatment after 1:55 minutes. The other five administrations were completed successfully, with no further SAEs. Other reported drug related AEs were primarily Grade 1 that resolved/recovered without sequelae. Clinical immune blood biomarkers post UNO101 treatment demonstrated modulation of the tumor microenvironment by upregulating of cytotoxic T-cells (11.1%), T-central memory cells (190.6%) as a percent of total T-cells, and dendritic cells (231.4%) as a percentage of WBCs, from baseline to Day 21. Further, T-regulatory cells (38.0%) were downregulated as a percentage of total T-cells from baseline to Day 21. Based on available physical examination and caliper measurements, clinical presentation on Day 7 on two subjects, significant clinical responses were observed. Conclusions: To date,a single dose of UNO101 at 25,000 ppm is well tolerated, with biomarkers suggesting immune action within the tumor microenvironment, trending in a favorable direction on Day 21 in a heavily pre-treated population. Additional UNO101 single dose of 50,000 ppm, and possibly 100,000 ppm, will be further evaluated for safety/tolerability, impact on immune biomarkers, and preliminary efficacy. Clinical trial information: NCT05351502 .

A phase 1, multi-center, safety, feasibility, and preliminary efficacy study evaluating a single dose of UNO101 in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies.

TPS2686 Background: Tumor ablation is a minimally invasive technique commonly used to treat solid tumors in the liver, kidney, bone, and lung and is usually based on thermal and nonthermal approaches. Local and in-situ tumor ablation methods demonstrate enhanced anti-tumor immune responses resulting in the destruction of residual malignant cells in primary tumors and distant metastases. Nitric oxide (NO) is a colorless gas and a short-lived free radical. It is a ubiquitous, endogenously generated gas implicated in the homeostatic regulation of physiological processes. Preclinical studies evaluating the effect of high concentration exogenously administered NO demonstrated its anti-cancer properties and suggested that it may serve as a potent tumoricidal agent. We have previously shown that treating mouse colon carcinoma (CT26) tumor-bearing mice with ultra-high concentrations of nitric oxide (UNO101) upregulates innate and adaptive immune cells both locally and systemically. Beyond Cancer is currently conducting a first-in-human, first-in-class, Phase 1 safety, feasibility, and preliminary efficacy clinical study of UNO101 at multiple institutions in Israel. Methods: The study is a 2-part Phase 1 trial with a Dose Escalation and a Dose Expansion portion (NCT05351502). A conventional 3+3 dose escalation will evaluate three cohorts of UNO101 single dose: 25,000, 50,000 and 100,000 parts per million (PPM) delivered intratumorally over 5 minutes in subjects with an ECOG PS of 0–3, at least 3 months of life expectancy, with relapsed or refractory unresectable primary or metastatic cutaneous and subcutaneous measurable solid tumors being eligible for enrollment. Upon determination of the maximum tolerated dose or biological effective dose, whichever occurs first, the proposed recommended Phase 2 dose will be further evaluated in the Dose Expansion portion of the study. RECIST version 1.1 and iRECIST will be utilized to assess the rate of malignant tumor response after UNO administration and toxicity will be graded per NCI CTCAE version 5.0. Evaluation of response per itRECIST will also be explored. Up to thirty-eight enrolled subjects are anticipated. Cohort 1, 25,000 PPM have been completed without a reported DLT. Enrollment to Cohort 2, 50,000 PPM, began in January 2024. This study was approved by Israel Ministry of Health (IMOH) as well as the participating institution’s Ethics Board. Written informed consent was obtained for all enrolled subjects and a copy of the written consent is available for review. Clinical trial information: NCT05351502 .

Incidence and survival rates of primary cutaneous malignancies in Korea, 1999-2019: A nationwide population-based study.

Primary cutaneous malignancies are among the most commonly diagnosed types of cancer worldwide. We aimed to examine the incidence and 5-year survival rates of all types of primary cutaneous malignancies in the Korean population. Data from the Korean Nationwide Cancer Registry from 1999 to 2019 were analyzed. The crude incidence rates, age-standardized incidence rates, and 5-year relative survival rates of each type of skin cancer were calculated. A total of 89 965 patients were diagnosed with primary cutaneous malignancies, which was a 7-fold increase from 1999 to 2019. The age-standardized incidence rates increased 3.4-fold in basal cell carcinoma (3.7/100 000 person-years), 2.0-fold in squamous cell carcinoma (1.6/100 000 person-years), 12.0-fold in Bowen disease (1.2/100 000 person-years), and 1.8-fold in malignant melanoma (0.7/10 000 person-years) in 2019. Average annual percentage changes in age-standardized incidence rates were statistically significant in basal cell carcinoma (15.8%), Bowen disease (5.8%), squamous cell carcinoma (5.1%), malignant melanoma (1.2%), melanoma insitu (1.1%), dermatofibrosarcoma protuberans (1.2%), mycosis fungoides (0.5%), primary cutaneous CD30+ T-cell proliferations (0.5%), adnexal and skin appendage carcinoma (0.4%), extramammary Paget's disease (0.2%), and Merkel cell carcinoma (0.2%). The 5-year relative survival rates were the highest in basal cell carcinoma (103.3%), followed by dermatofibrosarcoma protuberans (99.7%) and mycosis fungoides (96.6%), and lowest in angiosarcoma (24.7%). The 5-year relative survival rates steadily increased in extramammary Paget's disease (23.6%), cutaneous B-cell lymphoma (21.3%), mycosis fungoides (20.2%), extranodal NK/T-cell lymphoma, nasal type (18.1%), and malignant melanoma (16.1%) from 1996-2000 to 2015-2019. Most primary cutaneous malignancies have increased in incidence and survival rates in the Korean population, but to varying extents depending on the type of skin cancer.

Hippocampal-Sparing Radiotherapy in Primary Sinonasal and Cutaneous Head and Neck Malignancies: A Feasibility Study

Patients with primary sinonasal and cutaneous head and neck (H&N) malignancies often receive meaningful hippocampal doses, but the hippocampus is not a classic avoidance structure in radiation planning of these primary sites. This series characterizes the feasibility and tradeoffs of hippocampal-sparing radiotherapy (HSRT) for patients with primary sinonasal and cutaneous H&N malignancies. We retrospectively identified patients at a single institution treated definitively for primary sinonasal or cutaneous malignancies of the H&N. Each patient received (chemo)radiation and all received clinically-significant radiation dose to one or both hippocampi. We created new HSRT plans for each patient with intensity-modulated radiotherapy using original target and organ-at-risk (OAR) volumes. Hippocampi were contoured based on Radiation Therapy Oncology Group guidelines. Absolute and relative differences in radiation dose to the hippocampi, planning target volumes (PTV), and OARs were recorded. We used paired-samples t-tests to compare hippocampal and PTV dosimetric measures with and without HSRT. Thirty-seven patients were included (22 sinonasal, 11 cutaneous H&N, and 4 parotid primary tumors). Median prescription dose was 6600cGy (range: 5000-7440cGy). The most common fractionation regimens were 200cGy/fraction daily (51%, 19/37 patients) and 120cGy/fraction twice daily (41%, 15/37 patients). There were significant decreases in hippocampal Dmax and D100% using HSRT without compromising PTV coverage (Table 1). HSRT resulted in a relative increase of mean lacrimal gland dose by an average of 3.8%, optic chiasm Dmax by 1.3%, and whole brain Dmax of 1.2%. However, other OAR doses were lower with HSRT, including parotid gland mean dose, lens Dmax, optic nerve Dmax, cochlea mean dose, brainstem Dmax, and whole brain mean dose. HSRT is feasible and results in meaningful radiation dose reduction to the hippocampi without reducing PTV coverage or increasing dose to other OARs. The hippocampi should be regularly included as avoidance structures when treating primary sinonasal and cutaneous H&N tumors with radiation. We suggest target hippocampal constraints of Dmax < 1600cGy and D100% < 500cGy when feasible (without compromising PTV coverage). The clinical significance of HSRT in patients with primary H&N tumors should be investigated prospectively.

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.

Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies. The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis. Two case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition. There is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.

Port-site Metastasis from Gall Bladder Adenocarcinoma with Squamous Differentiation Following Laparoscopic Cholecystectomy: A Rare Case Report

Port site cutaneous metastasis of gallbladder cancer is an exceedingly infrequent phenomenon with very few cases reported in the past. Herein, we report a case of port site cutaneous metastases of gallbladder adenocarcinoma in a 57 years old female. Physical examination revealed a non healing ulcer in the epigastric region. FNA was suggestive of poorly differentiated carcinoma. Biopsy demonstrated atypical cells. Immunohistochemical analysis showed diffuse cytoplasmic staining with CK 7 and p63 showed focal nuclear positivity in tumour cells. This confirmed the diagnosis of metastastatic gall bladder adenocarcinoma with squamous differentiation. Diagnosis in such a case can be very challenging as the differential of primary cutaneous malignancies should also be kept in mind.

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis

A Histopathological Study on Primary Cutaneous Malignancies of Surface Epidermis

Introduction: Skin is a complex organ, it’s intricacy allows for a wide range of malignancies. Skin types, geographical latitudes, occupational exposure, sun exposure, and skin protection behaviors may all contribute to skin cancer trends and rates. Some cancers are easily recognised clinically, whereas others require a combination of clinical and histopathological correlation. Aim: To determine the spectrum and frequency of various primary cutaneous malignancies of the surface epidermis based on histomorphological characteristics, Guntur, Andhra Pradesh, India. Materials and Methods: The present retrospective study was conducted in the Department of Pathology at Katuri Medical College and Hospital, Guntur, Andhra Pradesh, India. The study covered a total of 30 cases of primary cutaneous malignancies of surface epidermis with histopathological confirmation. The study samples included from January 2019 to June 2021 over a 30-month period and the data was collected and analysed in the month of August 2021 and September 2021 from the histopathology records. Typing of these tumours was done by using Haematoxylin and Eosin (H&amp;E) stained sections. All the cases were analysed and divided according to the patient’s age, gender, and tumour location, as well as the tumour’s histological characteristics. Descriptive statistics were used and data was tabulated in frequency and percentages. Results: A total of 30 cases of primary cutaneous malignancies of surface epidermis, were studied, of which 21 (70%) cases were keratinocyte derived cancers and 6 (20%) cases were melanocyte derived cancers. The most frequent keratinocyte tumour was squamous cell carcinoma followed by Basal cell carcinomas. Present study documented three cases of melanocarcinomas, of which two were basomelanocytic tumors and one case was squamomelanocytic tumors. There was slight male preponderance with male to female was 3:2. Most cases distributed in the age group of 61-80 years, followed by 41-60 years. The most frequently involved anatomical site was the head and neck region followed by the trunk region. Conclusion: Skin cancers, at times, may be difficult to diagnose clinically. Hence, histopathological examination is a must for definitive diagnosis. This study highlighted the critical role of histopathology in accurately classifying tumours into distinct morphological types which enables the clinician to make the correct diagnosis and formulate appropriate treatment plan.

34929 Cutaneous adenocarcinoma mimicking hidradenitis suppurativa

Cutaneous metastasis of visceral malignancies is uncommon and often indicates a poor prognosis. Immunohistochemical staining can help distinguish between cutaneous metastasis and primary cutaneous malignancy. We present a case report of a 56-year-old patient with a notable past medical history of metastatic disease of unknown primary and hidradenitis suppurativa who was evaluated for new lesions on the right axilla. The 2 exophytic red papulonodular lesions on the right axilla were noted to have no drainage or fluctuance.

Venous Flap Reconstruction following Wide Local Excision for Primary Cutaneous Malignancies in Extremities.

Background:Cutaneous malignancies in the extremities are relatively common, and radical treatment such as ray amputation was performed for certain advanced skin cancer cases in the past. The concept of surgical treatment of primary cutaneous malignant tumor has gradually changed, and preservation of the extremity by performing the appropriate excision and reconstruction became possible. Various reconstructive methods after the resection of malignant tumors such as skin grafts, local flaps, and free flaps, including perforator flaps have been noted. Due to limitations and some disadvantages of these reconstructive materials for extremities, the arterialized venous flap arose as an alternative method. The arterialized venous flap, which has arterial inflow through an afferent vein perfusing the flap and venous outflow through the efferent veins, is considered to function as a great reconstructive material for distal extremities. Although efficacy of this flap has been noted in the past, usage of the flap considering the oncological aspects and application of the flap to the toes and feet have never been reported.Methods:Thirteen reconstructive cases from October 2005 to October 2016 using venous flaps after excision of primary cutaneous malignancy in the distal extremities were performed in our institution.Results:For all cases, satisfactory functional and cosmetic outcomes were observed.Conclusions:Reconstruction using the arterialized venous flap is considered a reliable and versatile method. Careful application of this flap satisfies functional, cosmetic, and oncological aspects of all distal extremities with cutaneous malignancy.

Cytohistological and immunohistochemical correlation of cutaneous neoplastic lesions: Three year retrospective study

: Neoplastic lesions in cutaneous and subcutaneous region comprise a large group of benign and malignant entities of different lineage. Clinical, morphological features and prognosis of these lesions differ a lot. For diagnosis FNAC (Fine needle aspiration cytology) is the first technicque applied followed by histology, immunohistochemisty (IHC) and so on.: Cytological evaluation of cutaneous and subcutaneous neoplasms and correlate with histopathology and IHC. Study of all palpable cutaneous and subcutaneous swellings presenting to cytology OPD (Out patient department) with further histopathological correlation in the three-year duration.: FNA cytosmears of the cases stained with leishman stain in most of cases. Histopathological and IHC correlation done in available cases.: The data are expressed in descriptive statistics measures such as percentages and proportions. Out of 1032 total cases, most of the cases were benign (94.3%) with fewer malignant cases (5.7%). Lipomas 562(56.31 %) were the largest group among benign lesions followed by benign spindle cell lesions 286(28.65%). Metastatic (22, 64.7%) lesions were more in number than primary cutaneous malignancies (12,35.2%). Among adenocarcinomas, 4 metastatic cases (0.38%) from lung and breast each and among squamous cell carcinomas (SCC), 7(0.67%) primary SCC were seen. Biopsy correlation was available in 134(12.98%) cases and IHC done in 14(1.35%) cases.: Cutaneous neoplasms though benign in most of the cases, can be of critical aetiology with dismal prognosis. Hence they should not be taken lightly and diagnosed specifically with the help of imaging and cyohistological study whenever needed.

Cardiotoxicity of Systemic Melanoma Treatments.

Melanoma is the least common but most dangerous skin cancer, accounting for 75% of all deaths from a primary cutaneous malignancy, with incidence rates rising significantly over the last decade. Traditional treatments for melanoma including interferon and cytotoxic chemotherapy had marginal efficacy. With the advent of targeted and immunotherapies, the prognosis for patients with advanced melanoma has significantly improved including those with metastatic disease to the heart. BRAF and MEK inhibitors as well as immune checkpoint inhibitors have become front line therapy for eligible patients with metastatic melanoma and have led to long-term durable response and in some cases can be curative. Despite these oncologic advances, various treatment-limiting side effects can occur. In particular, cardiovascular toxicities can contribute to overall morbidity and mortality in these patients. Toxicities range from asymptomatic QT prolongation and mild LV dysfunction to fulminant myocarditis and potentially life-threatening arrhythmias. A multidisciplinary approach to the care of these patients which includes cardio-oncology evaluation is necessary to develop both risk mitigation and treatment strategies to ensure patients continue receiving necessary and effective melanoma treatments while minimizing long-term adverse cardiovascular effects.

Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: a protocol for a systematic review and meta-analysis

Abstract Electrochemotherapy has emerged as a valuable tool in the treatment of cutaneous malignancies that are unamenable to surgical resection. Despite growing recognition and recommendation in national guidelines, to date, no Level 1 evidence exists comparing its use to radiotherapy in the management of cutaneous malignancies. A systematic review and meta-analysis will be undertaken in line with the Cochrane Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. A comprehensive search strategy will be applied to MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov from the time period from inception to December 2021. Supplementary searches of the grey literature will also be undertaken. Studies in humans which compare treatment with electrochemotherapy to radiotherapy and report tumour response with at least a 4-week follow-up will be eligible. Studies will be included regardless of publication language or country of origin. Screening of studies and data extraction will be undertaken independently by two authors. Our primary outcome will be tumour volume response according to Response Evaluation Criteria in Solid Tumors. We will also extract any secondary outcomes reported, such as patient-reported outcome measures, pain, toxicity/adverse events and progression-free survival. Included studies will be assessed for risk of bias using recognized tools. Evidence quality will be appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. If studies are of acceptable clinical homogeneity and suitable data is extracted, a meta-analysis will be performed. If adequate data are present, various subgroup analyses will be performed. Publication bias will be assessed using a funnel plot and Egger’s test. PROSPERO CRD42021285415

649Personal history of keratinocyte carcinoma is a marker of inherited cancer risk: Mendelian randomization analyses

Abstract Background A personal history of keratinocyte carcinoma (KC) has been reported as a risk factor for developing subsequent primary cutaneous and non-cutaneous malignancies. However most evidence to date stems from observational studies which are prone to bias, confounding and reverse causation. Our aim was to examine this association using different Mendelian randomization (MR) approaches. Methods We performed a one-sample MR analysis using individual-level data from the UK Biobank (n = 394,306). This analysis was then validated in an independent dataset in the QSkin cohort (n = 16,896). Using 64 independent genetic variants known to be associated with KC, we generated a polygenic risk score (PRS) for each participant in the UK Biobank and the QSkin cohort. We then performed two-sample MR analyses using genome-wide association study (GWAS) summary statistics. We tested the association between genetically predicted KC and risk of subsequent cancer using logistic regression. Results Results from one-sample MR analyses in the UK Biobank indicated that a personal history of KC was significantly associated with cancer overall (excluding melanoma) (OR: 1.15, 95% CI: 1.10-1.20, per doubling the prevalence of KC). The results from the two-sample MR corroborate the findings from the one-sample MR, although the risk estimate was lower (OR: 1.05, 95% CI: 1.03-1.07). Conclusions Our MR analyses suggest that genetically predicted KC is a risk factor for developing subsequent primary malignancies. Key messages A personal history of KC may serve as a proxy marker of inherited cancer risk.

Primary cutaneous malignancies in nonalbino and albino Africans.

The pigmented skin of black Africans has been credited with reduction in risk of skin cancer. African albinos have inherited defects in skin melanin deposition, which predisposes them to ultraviolet radiation-induced cutaneous carcinogenesis. We compared the manifestation of skin cancers between albino and nonalbino Africans aiming to describe the effect of pigmentation or lack of it on the epidemiological characteristics of skin cancer in Africans. Cutaneous malignancies seen in our institution over a 19-year period were analyzed using SPSS statistical software. Results were presented in tables of frequencies. Continuous variables were presented as mean with standard deviation and compared with independent sample t-test and ANOVA. Alpha level of <0.05 was considered significant. There were 86 albinos and 364 nonalbinos in the study. Mean age (SD) at presentation for albinos was 41 (14)years and for nonalbinos 52 (17)years. Albinos had most tumors in the head and neck region and upper extremities. For nonalbinos, lower extremities followed by anogenital region were the most common body site of cutaneous malignancy. Squamous cell carcinoma was the most common type of skin cancer in the albino and nonalbino patients. No case of malignant melanoma was diagnosed in the albino group. Albino skin cancer patients were much younger than nonalbinos. Albinos and nonalbinos differ in body site distribution of skin cancers. Distribution of keratinocyte carcinomas in albinos parallels the reported findings in Caucasians. Albinos may have some level of protection from cutaneous melanoma in spite of hypomelanized skin.

Primary cutaneous adenoid cystic carcinoma: Characterizing US demographics, clinical course, and prognostic factors

To the Editor: Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare primary cutaneous malignancy, first described by Boggio1 in 1975. Histologically, PCACC presents with basophilic cells having adenoid or cribriform patterns due to true lumina within islands that are surrounded by modified myoepithelial cells and prominent basement membrane material.2,3 Given the somewhat conflicting data of indolent tumors as well as tumors with more aggressive behavior, we studied the incidence and survival patterns for patients with PCACC in the United States.

Cutaneous Squamous Cell Carcinoma in Faghihi Hospital Patients (Shiraz, Iran) in 2015 - 2016: Epidemiological Study

Background: Cutaneous Squamous Cell Carcinoma (cSCC) is an invasive primary cutaneous malignancy and the second common cancer among whites. Objectives: To define the frequency and epidemiologic features of cSCC. Methods: This study was carried out on 311 patients referred to the Department of Dermatology at Faghihi Hospital of Shiraz, Southwest Iran, between 2015 - 2016. cSCC was diagnosed by pathologists using the standard criteria. The reports were collected along with general information such as age, sex, location, type, and depth of invasion; then it was analyzed by using the statistical software known as SPSS version 23.0 and Minitab software version 18. Chi-square test was used to evaluate the statistical significance. A P value lower than 0.05 was considered as significant. Results: The age range of patients was 21 - 95 years old with an average age of 67.63. The sex ratio (male to female) was 2.87 for the total number of cases. The most common stage was well differentiation 97 (31.2%). The most frequent tumor thickness was between two to four millimeters and the most frequent lesion locations were the nose and then the scalp. Conclusions: The frequency of cSCC increased over the years in regards to patients that were referred to the Faghihi Hospital. This results along with other data which are available from other hospitals and medical centers confirm that the frequency of cSCC is increasing in Iran and plan for management of cSCC is essential, nationally.

Cool Atmospheric Plasma (J-Plasma) and New Options for Facial Contouring and Skin Rejuvenation of the Heavy Face and Neck.

Treating patients with heavy or thick features comes with challenges not present in those patients lacking these physical characteristics. The authors report our experience with cool atmospheric plasma for facial contouring and skin rejuvenation of the heavy face and neck including rhinophyma. Cool atmospheric plasma is generated by running helium gas over radiofrequency energy. The resulting plasma is a fourth state of matter and has enhanced clinical effects for ablation and thinning of skin and soft tissues as well of contouring and tightening of deeper soft tissues and fascia. Cool helium plasma has been a very effective tool for skin rejuvenation and skin tightening as well as using it as a tool for nonexcisional microinvasive face and neck rejuvenation. Future research may indicate that it can help treat primary or recurrent superficial cutaneous malignancies.