Treatment Of Basal Cell Carcinoma Research Articles

Optimizing surface mould brachytherapy for treatment of nasal basal cell carcinoma using customized applicators

PURPOSESurface mould brachytherapy (SMBT) is ideal in treating superficial skin cancer over the curved surface of the nasal ala. We describe the process of initiating and optimizing SMBT treatment at our institution including clinical workflow, generation of three dimensional (3D) printed custom applicators, and clinical outcomes. METHODS AND MATERIALSPlanning CT scans were used to acquire images for delineating target volumes. The applicator was designed with customized catheter positioning (3–5mm from target) to cover target volume while sparing dose to organs at risk (OAR) such as adjacent skin and nasal mucosa. Applicators were 3D printed, with transparent resin to aid visualization of underlying skin. Dosimetric parameters evaluated included CTV D90, CTV D0.1cc, and D2cc to OARs. Clinical outcomes assessed were local control, acute and late toxicity (Common Terminology Criteria for Adverse Events v5.0 [CTCAEv5.0]), and cosmesis (Radiation Therapy Oncology Group [RTOG]). RESULTSTen patients were treated with SMBT with a median followup of 17.8 months. Dose prescription was 40 Gy in 10 daily fractions. Mean CTV D90 was 38.5 Gy (range 34.7–40.6), mean CTV D0.1cc 49.2 Gy (range 45.6–53.5), which was <140% of the prescription dose in all patients. Treatment was well tolerated, with acceptable Grade 2 acute, Grade 0–1 late skin toxicity, and good-excellent cosmesis for all patients. Two patients experienced local failure, and both underwent surgical salvage. CONCLUSIONSSMBT was successfully planned and delivered for superficial nasal BCC using 3D printed custom applicators. Excellent target coverage was achieved while minimizing dose to OAR. Toxicity and cosmesis rates were good-excellent.

5-Fluorouracil for Treatment of Vocal Fold Scar

Vocal fold (VF) scar can result from trauma, neoplasm, inflammatory processes, congenital causes, surgery and other etiologies. In general, once the vibratory margin of the VF has been scarred, it has not been possible to return VF function to normal; but often it can be improved. The drug 5-fluorouracil (5-FU) is a pyrimidine antimetabolic that has many clinical applications ranging from systemic chemotherapy to topical treatment of actinic keratosis and basal cell carcinoma of the skin. Local injection with 5-FU also has been used for hypertrophic scar and keloids. 5-FU was shown to have benefit in animal models of VF scar and subglottic stenosis. The present study aimed to evaluate the effect of 5-FU injection on VF vibratory function in patients with VF scar. Outcomes of 5-FU injection were compared to controls injected with dexamethasone. Adult voice center patients who had undergone VF injection with dexamethasone or a series of three 5-FU injections for treatment of VF scar were included in the study. Postoperative outcomes included percentage of subjects demonstrating improvement after injection, change in scar size, glottic closure, and VF stiffness, as well as digital image analysis measurements of mucosal wave. Outcomes were compared between subjects who received 5-FU and those who received dexamethasone. There were 58 VFs injected with 5-FU and 58 historical controls injected with dexamethasone. Baseline subject characteristics and etiology of scar did not differ significantly between the 5-FU and dexamethasone cohorts, except that scar size was greater in the 5-FU group and mucosal wave was worse at baseline. After a series of three 5-FU injections, 61.22% improved, 8.16% demonstrated no change, and 30.61% worsened. In the dexamethasone cohort, 51.06% improved, 0.00% demonstrated no change, and 48.94% worsened. The response differed significantly between the 5-FU and dexamethasone cohorts, with a greater proportion of subjects who underwent 5-FU injection demonstrating improvement postoperatively. In the 5-FU cohort, 32.76% of subjects previously had undergone and failed dexamethasone injection for VF scar: and within that group 84.21% improved, 5.26% demonstrated no change, and 10.53% worsened following 5-FU injection. On digital image analysis, the percent improvement in postoperative mucosal wave was significantly greater in the 5-FU cohort compared to the dexamethasone group, which demonstrated a worsening of mucosal wave. A series of three intralesional injections with 5-FU outperformed dexamethasone for improving mucosal wave in patients with VF scar. A prior failed trial of dexamethasone injection predicted a favorable response to 5-FU. Further research is encouraged to confirm or refute these findings.

A critical re-evaluation of Mohs micrographic surgery for a facial basal cell carcinoma in older adults: Should we waive this treatment in certain patients?

Skin cancer incidences are increasing. Treatment for basal cell carcinomas (BCCs) can be questioned in certain patients. Treatment options are various, but Mohs micrographic surgery (MMS) has the highest cure rate. It is, however, time-consuming and results in high logistical burden and treatment costs for both patients and society. This study critically re-evaluates MMS for facial BCCs in older adults. The main objective is to examine all clinical, tumour and patient characteristics in relation to safety and survival to detect a subgroup in which MMS was not the best choice. The overall aim is to identify characteristics that support clinical decision-making in daily practice. Patients that received MMS between November 1998 and December 2012 were included. Only patients >75 years with a facial BCC were withheld for analysis. This is a retrospective cohort study, since evaluating the outcome of MMS in accordance with life expectancy is the main objective. Patient charts were evaluated towards comorbidities, complications and survival. This cohort comprises 207 patients. Median survival was 7.85 years. The age-adjusted Charlson comorbidity index (aCCI) was divided into low/medium scores (aCCI < 6) and high scores (aCCI ≥ 6). Median survival was 11.58 years in the low aCCI group and 3.60 years in the high aCCI group (p < 0.001). There was a very strong association between high aCCI and survival (HR, 6.25; 95% CI, 3.83-10.21). Other characteristics were not associated with survival. Clinicians should assess the aCCI in older patients presenting with a facial BCC before deciding if MMS is an eligible treatment option. High aCCI has shown to be an indicator for low median survival, even in MMS patients with usually high functional status. MMS should be waived as treatment in older patients with high aCCI scores in favour of other, less intensive and less expensive treatment options.

Chemotherapeutical treatment of basal cell carcinoma with bleomycin via microinfusion of the drug into the skin (MMP®)

BackgroundBleomycin is a chemotherapeutical drug used to treat several neoplasias, including non-melanoma skin cancer; it is effective in the treatment of basal cell carcinoma (BCC) via intralesional infiltration. Transdermal drug delivery, which includes technologies such as CO2 Laser, Dermapen, Dermaroller and MMP®, delivers the desired medication to treat skin neoplasias and also acts in skin rejuvenation. ObjectiveTo treat BCC lesions using bleomycin via MMP®. MethodsNinety-eight BCC lesions in different anatomical areas were treated using MMP® technology to administer and uniformly distribute bleomycin throughout the lesion and in the established safety margin. ResultsThe cure rate after six months was 96.94%; and recurrences were not associated with lesion size and/or depth. Adverse effects were the expected ones. Study limitationsThe follow-up time was only six months. ConclusionThis therapeutic route showed to be promising and effective.

Comparison of the effectiveness of 5-Fluorouracil and modified Carnoy's solution in reducing the recurrence of odontogenic keratocyst.

Odontogenic keratocysts (OKC) has a high potential for recurrence. Resection is currently the only fool-proof method to ensure that recurrence does not occur; however, it drastically affects the patient's function and aesthetics. Application of modified Carnoy's solution (MCS) as an adjunct to reduce the recurrence rate is currently in vogue. 5- Flurouracil (5-FU) is an anti-metabolite that has been used in the treatment of basal cell carcinoma and is relatively safer than MCS. The present study aims to compare the effectiveness of 5-UC and MCS in reducing the recurrence rate in OKC.. A total of 42 OKCs were enucleated followed by application of MCS (control group, n=21) or 5-FU dressing (study group, n=21) following enucleation. Pain, swelling, temporary and permanent paresthesia paresthesia, bone sequestrum formation, osteomyelitis and recurrence in both groups were evaluated at periodic intervals up to 12 months post-surgery. There was no significant difference in terms of pain, or swelling in both groups. Permanent paresthesia and recurrence rates were higher in patients treated with MC but the difference was not statistically significant. 5-FU is an easy-to-use, feasible, biocompatible and cost-effective alternative for MCS in the management of OKCs. Treatment with 5-FU, therefore, reduces the risk of recurrence and also the post-surgical morbidity associated with other treatment procedures.

Abstract CT115: Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region: A phase I clinical trial

Abstract Immunotherapies with monoclonal antibodies (checkpoint inhibitors) are currently being intensively researched and have led to excellent response in many cases in various tumors. Another potential approach to immunotherapy is the targeted intratumoral administration of interleukin 12 (IL -12), a cytokine with proven anti-tumor activity. Due to its immunomodulatory effect, it can be used as an immunostimulatory component for in situ vaccination of local ablative therapies. We have developed a phIL12 plasmid without antibiotic resistance markers using a transgene for the human IL -12 p70 protein. The plasmid can be introduced intratumorally by gene electrotransfer. In gene electrotransfer, electrical pulses are applied to the tumor to deliver the plasmid DNA into the cells. Based on nonclinical studies of safety, pharmacokinetics, pharmacodynamics, tolerability, and immunogenicity, a phase I clinical trial of phIL12 gene electrotransfer was conducted (ISRCTN15479959, ClinicalTrials NCT05077033). The primary objective of the study is to evaluate the safety and tolerability of phIL12 gene electrotransfer in the treatment of basal cell carcinoma in patients with operable tumors of the head and neck. The study, an exploratory, dose-escalating Phase I study, will enroll 9 patients in three dose-escalating cohorts. Treatment consists of plasmid injection followed by application of electrical pulses to the tumors. Patients are monitored for 30 days, with tumors removed if a complete response is not achieved. To date, two cohorts of patients have completed the study. No adverse effects or treatment-related toxicities have been observed, and treatment has been well tolerated by patients. The results of this study will provide the basis for the use of phIL12 gene electrotransfer as adjuvant therapy to local ablative therapies to enhance their local effect and elicit a systemic response. Citation Format: Gregor Sersa, Maja Cemazar, Crt Jamsek, Primoz Strojan, Tanja Jesenko, Masa Bosnjak, Ales Groselj. Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region: A phase I clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT115.

Treatment of penoscrotal basal cell carcinoma - an institutional retrospective review.

Basal cell carcinoma (BCC) of the sun-protected genital region is rare. We examined all penoscrotal BCC at a single institution over an 18-year period. A total of 7 cases were identified, 5 scrotal and 2 penile. Four cases (57%) were treated with Mohs micrographic surgery (MMS) and 3 cases (43%) with conventional excision. A prior retrospective review of vulvar BCC at our institution during the same time period showed that MMS was utilized in 4 (11%) of 35 cases. Functional preservation is vital when performing surgery on the genitals and tissue-sparing MMS provides optimal tumor clearance and outcomes for both males and females.

Efficacy of Photodynamic Therapy with Chlorine-Based Photosensitizer in the Treatment of Basal Cell Carcinomas

The aim of this study is to evaluate a safety and antitumor efficacy of photodynamic therapy (PDT) with chlorine-based photosensitizer (PS) for treatment patients with basal cell skin carcinomas (BCC).&#x0D; Material and Methods: The work was performed on the basis of the Department of hyperthermia and photodynamic therapy. The object of the study were 172 patients with a verified diagnosis of BCC (T1N0M0, I stage), who received treatment from 2007 to 2022. PS «Photolon» (RUE «Belmedpreparaty», Republic of Belarus) was administrated intravenously at a dose of 2.0-2.5 mg/kg. The session of PDT was performed 2.5-3 h after intravenous injection of PS using semiconductor lasers (λ=660±5 nm) with exposure doses 50-250 J/cm² and power density – 0.15-0.5 W/cm². Frequency and severity of side effects after treatment session was assessed based on the criteria CTCAE (Version 4.03; 2010). The antitumor efficacy was evaluated 3 months after treatment. Clinical outcome was evaluated visually and morphologically by cytological or histopathological examination. Performance criteria were as follows (according to WHO, 1979).&#x0D; Results: The phenomenon of skin phototoxicity due to violation of the light regime (hyperemia, burning, slight swelling of the soft tissues of the face; CTCAE, I-II grades) was registered in 5.8% of cases (n=10). Serious adverse reactions (anaphylactic shock, Quincke's edema, severe pain syndrome) after the administration of PS and photoirradiation were not identified. Complete and partial regressions of tumors was observed in 93.0% and 4.7% of patients, respectively. The objective answer was 97.7%. The frequency of local relapses of the disease 1, 2, 3, 4 and 5 years after PDT was 3.1%, 3.1%, 4.6%, 4.6% and 6.9%, respectively.&#x0D; Сonclusion: PDT is a well-tolerated and highly effective therapeutic option in patients with BCC.

Non-Invasive Treatment of Basal Cell Carcinoma: Photodynamic Therapy Following Curettage.

To investigate the effectiveness, safety, patient satisfaction, and cosmetic outcome of Methyl Aminolevulinate-Photodynamic Therapy (MAL-PDT) following curettage in order to make recommendations for its use in dermatology practices. A retrospective chart review of patients who received MAL-PDT following curettage for the indication of basal cell carcinoma (BCC) between 2009 and 2016 at a single private clinic in Ontario, Canada. Two hundred and seventy-eight patients with 352 BCC lesions were included, consisting of 44.2% males (n=123) and 55.8% females (n=155) with a mean age of 57.24 years. The primary outcome measurement consisted of the cure rate. Secondary outcome measurements included side effects, patient satisfaction, and cosmetic outcome, as reported in the medical charts. The overall cure rate was 90.3% (n=318). After controlling for age, sex, and lesion type, nasal lesions were approximately 2.82 (95% CI: 1.24-6.40, P=0.01) times more likely to experience a recurrence. 18.3% of patients (n=51) reported side effects, the most common being burning (n=19). Of those who expressed satisfaction, 100% (n=25) reported being happy. Of lesions with cosmetic data, 90.3% displayed a good response (n=149). MAL-PDT following curettage is an effective and safe treatment option for BCC lesions with a good cosmetic outcome and suggested high patient satisfaction. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7133.

Cemiplimab-Associated Sinusoidal Obstruction Syndrome

A 58-year-old woman developed new-onset recurrent ascites after the recent initiation of cemiplimab for the treatment of advanced basal cell carcinoma. A comprehensive serological workup for viral, metabolic, and autoimmune causes was unrevealing. Transjugular liver biopsy demonstrated parenchymal changes consistent with a diagnosis of sinusoidal obstruction syndrome. While this is a condition commonly observed in patients after hematopoietic stem cell transplantation or use of chemotherapeutic agents, it should also be considered in patients who develop new-onset liver dysfunction after the initiation of checkpoint inhibitors.

Dermatosurgery - from surgical option to integral part of dermatologic therapy.

Dermatosurgery was long considered an isolated, and not always important, discipline within dermatology. As a therapeutic option, it was considered either the gold standard of first-line therapy, for example in basal cell carcinoma surgery and treatment of early-stage melanoma, or the last option, for instance in the treatment of warts. The fact that a profound change has taken place and that dermatosurgery is now an integral, equal, sometimes leading and always significant component of dermatology will be demonstrated in this review using three examples from geriatric dermatology, the treatment of hidradenitis suppurativa (acne inversa), and melanoma therapy. This review is supplemented by a section on the most important technique in dermatosurgery: microscopic (micrographic) surgery or Mohs Surgery.

Proposed guidelines for appropriate utilization of superficial radiation therapy in management of skin cancers. Zemtsov-Cognetta criteria.

To develop appropriate use criteria (AUC) for the treatment of basal cell and squamous cell carcinoma by superficial radiation therapy (SRT) technique. Delphi-type discussion of the experts. Presented in Figure 1. These AUCs are in compliance both with the position statement of the American Academy of Dermatology (AAD) and the ASTRO Clinical Practice Guideline on this subject. It is further recommended that SRT will be only performed by either a dermatologist who is board certified in Mohs surgery (MDS) and who had adequate SRT training or by radiation oncologists. Hopefully, this publication will stimulate further discussion on this topic.

Adequacy of surgical margins, re-excision, and evaluation of factors associated with recurrence: a retrospective study of 769 basal cell carcinomas

BackgroundAchieving adequate surgical margins and preventing recurrence are important in the treatment of basal cell carcinoma (BCC). ObjectivesThe objectives of this study were to evaluate the adequacy of surgical margins and the re-excision rates in patients with primary BCC who underwent standard surgical treatment using our proposed algorithm and to define the risk factors in patients with recurrent BCC. MethodsThe medical records of patients who were histopathologically diagnosed with BCC were reviewed. An algorithm created based on previous literature was used to determine the distribution of optimal surgical margins adequacy and re-excision rates. ResultsStatistically significant differences were observed between the cases with and without recurrence in age at diagnosis (p=0.004), tumor size (p=0.023), tumor location in the H zone of the face (p=0.005), and aggressive histopathological subtype (p=0.000). When the tumors were evaluated for adequacy of deep and lateral surgical margins and re-excision rates, higher rates of adequate excision (457 cases, 68.0%) and re-excision (43 cases, 33.9%) were noted for tumors in the H or M zone. Study limitationsInadequate follow-up of newly diagnosed patients in terms of recurrence and metastasis and the retrospective application of our proposed algorithm are the limitations of the present study. ConclusionsOur results showed that if BCC was detected at an early age and at an early stage, recurrence was lower. The H and M zones were the regions with the highest rates of optimal surgical outcomes.

Basal cell carcinoma in the elderly Cryosurgery or surgery – a case study with reference to the literature

Introduction&#x0D; The aging of society leads to an increase in the occurrence of basal cell carcinoma (BCC). BCC includes both superficial and nodular lesions with a good prognosis as well as foci that are difficult to treat and require a multidisciplinary approach. There are two basic methods of treating BCC, surgery to remove the tumor and cryosurgery. The paper presents a case of an 82-year-old female patient suffering from BCC in a non-advanced stage of the disease with the presentation of subsequent stages of treatment.Aim of the studyAn attempt was made to confront an alternative method of BCC treatment by cryosurgery with the first-choice procedure - surgical excision of the tumor with a margin of healthy tissues.Description of the caseAn individual clinical case study including the patient's medical records.ConclusionsThe work emphasizes the importance of comprehensive care for a patient diagnosed with BCC.Individualization of the diagnostic and therapeutic process is the basis for dealing with the elderly patient.

Intralesional Treatment of Basal Cell Carcinoma in a Genetically Inducible Mouse Model

Introduction: Patients with nevoid basal cell carcinoma syndrome (NBCCS), also termed Gorlin syndrome, develop numerous basal cell carcinomas (BCCs). Current treatment options include systemic hedgehog pathway inhibitors, with significant side effects when used long term, and multiple surgeries with the risk of scarring and sometimes even disfigurement over the long term. We have developed an intralesional treatment for BCC based on the intracellular delivery of an antisense oligonucleotide (ASO) targeting Gli1, the main protein active in the hedgehog pathway responsible for BCC. To test the efficacy of our treatment, we developed an inducible NBCCS-like mouse model, genetically modified at the level of the expression of the Ptch1 and p53 genes in the skin.&#x0D; Methods: The inducible mouse model uses Ptch1- and P53-knockdown mice irradiated with UVB three times a week until BCCs appear. These BCCs were treated once or twice a week with injections of an antisense oligonucleotide (ASO) targeting the production of the Gli1 protein, with and without the use of a peptide (the “Feldan shuttle") designed to introduce the ASO into the tumor cells. The evolution of the tumors was monitored several times a week with caliper measurements and photography. Following the treatments, the tumor site tissue was harvested and analyzed by both routine (H&amp;E) and specialized (IHC, IF) histologic methods .&#x0D; Results: Intralesional treatment of BCCs in the inducible mouse model using the ASO and peptide combination (FLD103) resulted in rapid and marked tumor regression, and sometimes complete eradication, over a few weeks. In addition, healthy perilesional skin appeared unaffected by the treatment, demonstrating targeted treatment specificity. The healed skin appeared grossly normal. Histologic examination of the treated sites after recovery showed no residual BCC as well as complete healing of the epidermis, dermis and subcutaneous tissue. We also observed that intralesional treatment with the ASO alone is not associated with tumor regression and in fact permits continued tumor growth.&#x0D; Conclusion: We have demonstrated the utility of a specific intralesional treatment for BCC in a genetically inducible mouse model. This alternative and novel treatment produces rapid results with normal healing of the treated site. This treatment could offer an attractive option for patients with multiple BCCs who wish to avoid systemic treatments or multiple surgeries.

Pulsed Dye Laser for Treatment of Basal Cell Carcinoma.

Patients with biopsy-proven BCC underwent two treatments with PDL at 6-week intervals at Berkshire Cosmetic and Reconstructive Surgery Center. Patients returned 6 weeks after the second treatment for evaluation for response to treatment. Follow-up examinations were conducted at 6, 12, and 18 months after treatment with PDL. Twenty patients with 21 biopsy-proven BCCs were treated with PDL at Berkshire Cosmetic and Reconstructive Surgery Center between 2019 and 2021. Nineteen BCCs had a complete response after two treatments, for a clearance rate of 90%. Two of the 21 lesions did not respond for an incomplete response rate of 10%. PDL is an effective nonsurgical treatment option in the management of BCC.

Expression of β-Catenin, E-Cadherin, and α-Smooth Muscle Actin in Basal Cell Carcinoma Before Photodynamic Therapy in Non-recurrent and Recurrent Tumors: Exploring the Ability of Predicting Photodynamic Therapy Outcome.

Photodynamic therapy (PDT) is an effective and cosmetically beneficial treatment of low-risk basal cell carcinomas (BCCs). To optimize PDT response, it is important to correctly select tumors. We sought to find markers that could identify such tumors beyond contributions from clinical and histological examination. Studies have shown that β-catenin, E-cadherin, and α-smooth muscle actin (SMA) expression can indicate BCC aggressiveness/BCC invasiveness. We wanted to use these markers in an explorative study to investigate whether they were differently expressed among non-recurring compared with recurring BCCs, to evaluate their ability of predicting PDT outcome. Fifty-two BCCs were stained with antibodies against β-catenin, E-cadherin, and α-SMA, and evaluated using immunoreactive score (IRS), subcellular localization, and stromal protein expression. Results showed that IRS of E-cadherin was significantly different among recurring compared with non-recurring BCCs and with area under a receiver operating characteristic curve of 0.71 (95% confidence interval: 0.56-0.86, p=0.025). Stromal β-catenin expression significantly increased among recurring BCCs. Some recurring BCCs had intense expression in the deep invading tumor edge. In conclusion, E-cadherin, and stromal and deep edge β-catenin expression were most prominent in BCCs that recurred post-PDT, suggesting they could potentially predict PDT outcome. Further studies are needed to investigate whether these results are of clinical value.

The use of a portable device for photodynamic therapy at home decreasing the patient's stay at hospital for small nodular basal cell carcinoma treatment

The use of a portable device for photodynamic therapy at home decreasing the patient's stay at hospital for small nodular basal cell carcinoma treatment

Nevoid Basal Cell Carcinoma Syndrome: A Review

Introduction: Gorlin syndrome (GS) or nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder characterised by development of multiple basal cell carcinomas (BCCs) at a young age. NBCCS occurs because of mutations in the PTCH1 gene, which functions as a tumour suppressor gene.&#x0D; Patients with GS can have varied manifestations, both cutaneous and extra-cutaneous. The most notable cutaneous manifestations are BCCs, which are also the most characteristic tumours in GS, and palmar/plantar pits. Besides the BCC, medulloblastomas are the second most characteristic malignant presentation.&#x0D; There are a set of criteria for the diagnosis of GS, which have a high predictability in making an accurate diagnosis of GS. Genetic testing for PTCH1 gene is one of the diagnostic criteria, which is positive in about 60% of patients.&#x0D; Patients with GS need a multidisciplinary approach. Mohs micrographic surgery is recommended for BCCs on high risk areas. SMO receptor inhibitors such as Vismodegib and Sonidegib have been approved by FDA for the treatment of advanced BCCs.

A pilot study using immunohistochemical staining to characterize dihydropyrimidine dehydrogenase expression in keratinocyte neoplasms

To the Editor: Topical 5-fluorouracil (5-FU) is a chemotherapeutic agent used to treat actinic keratoses (AK), superficial basal cell carcinoma, and squamous cell carcinoma in situ (SCCis). 5-FU is metabolized and inactivated by the enzyme dihydropyrimidine dehydrogenase (DPD), which is highly active in the liver but can be expressed in tumors as well. In several visceral malignancies, tumor DPD expression predicts response to systemic 5-FU: tumors with lower DPD expression correlate with higher 5-FU reactivity and better clinical response.1Horiguchi J. Yoshida T. Koibuchi Y. et al.DPD activity and immunohistochemical DPD expression in human breast cancer.Oncol Rep. 2004; 11: 65-72PubMed Google Scholar, 2Oi K. Makino M. Ozaki M. et al.Immunohistochemical dihydropyrimidine dehydrogenase expression is a good prognostic indicator for patients with Dukes' C colorectal cancer.Anticancer Res. 2004; 24: 273-279PubMed Google Scholar, 3Fukuda H. Takiguchi N. Koda K. Oda K. Seike K. Miyazaki M. Thymidylate synthase and dihydropyrimidine dehydrogenase are related to histological effects of 5-fluorouracil and cisplatin neoadjuvant chemotherapy for primary gastric cancer patients.Cancer Invest. 2006; 24: 235-241https://doi.org/10.1080/07357900600632082Crossref PubMed Scopus (18) Google Scholar Although this association has been studied in visceral tumors, the expression of DPD in keratinocyte neoplasms is not known. In this pilot study, we assessed DPD expression in benign, premalignant, and malignant keratinocyte neoplasms to assess the range and level of DPD activity. We performed DPD immunohistochemistry (IHC) staining of 26 superficial and nodular basal cell carcinomas (BCCs), 10 SCCis, 16 AKs, and 8 seborrheic keratoses from formalin-fixed paraffin-embedded specimens collected within the past 3 years. Diagnoses were confirmed by dermatopathologists (B.H., B.D.). DPD IHC was performed with anti-DPD antibody (Abcam #134922, 1:500 dilution). DPD expression was scored by intensity ranging from 0 to 3 by 2 authors (O.I. and B.D.), with hepatic staining as a positive control (Table I). Fisher’s exact test was used to compare DPD scores between classes of keratinocyte neoplasms (R software, version 4.0.3, https://www.r-project.org).Table IDihydropyrimidine dehydrogenase immunohistochemistry intensity score in patient samples (n = 60)DPD IHC intensity score0123Seborrheic keratosis0422Actinic keratosis1960SCC in situ0442Basal cell carcinoma21410Basal cell carcinoma includes both superficial and nodular subtypes. DPD IHC intensity was scored from 0 to 3 (0: no expression, 1: weak expression, 2: moderate expression, 3: strong expression). Fisher’s exact test P value = 3.95 × 10−9.DPD, Dihydropyrimidine dehydrogenase; IHC, immunohistochemistry; SCC, squamous cell carcinoma. Open table in a new tab Basal cell carcinoma includes both superficial and nodular subtypes. DPD IHC intensity was scored from 0 to 3 (0: no expression, 1: weak expression, 2: moderate expression, 3: strong expression). Fisher’s exact test P value = 3.95 × 10−9. DPD, Dihydropyrimidine dehydrogenase; IHC, immunohistochemistry; SCC, squamous cell carcinoma. The results showed a significantly enriched proportion of BCCs (81%, 21/26) displaying no DPD expression (DPD IHC intensity score of 0), compared to 0% (0/10) of SCCis and 6% (1/16) of AKs (P = 3.95 × 10−9, Table I). By contrast, 15% of BCC, 40% of SCCis, and 56% of AK had an intensity score of 1; 3% of BCC, 40% of SCCis, and 37.5% of AK had an intensity score of 2; and 0% of BCC, 20% of SCCis, and 0% of AK had an intensity score of 3 (Table I). The DPD intensity scores of seborrheic keratoses, a noncancerous keratinocyte neoplasm control, were distributed between 1 and 3. Our results suggest that DPD expression varies both within and across different keratinocyte neoplasms, and that a substantial fraction of BCC may have lower DPD expression compared to AK, squamous cell carcinoma (SCC), and seborrheic keratoses. Clinical studies have reported a wide range of efficacy in the use of topical 5-FU treatment for early-stage BCC and SCC, with success rates in SCC ranging from 27% to 93%.4Love W.E. Bernhard J.D. Bordeaux J. Topical imiquimod or fluorouracil therapy for basal and squamous cell carcinoma.Arch Dermatol. 2009; 145: 1431-1438Crossref PubMed Scopus (191) Google Scholar,5Neale H. Michelon M. Jacob S. et al.Topical 5% 5-fluorouracil versus procedural modalities for squamous cell carcinoma in situ and superficial basal cell carcinoma: a retrospective cohort analysis.J Am Acad Dermatol. 2022; 87: 423-425https://doi.org/10.1016/j.jaad.2021.08.045Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar While differences in treatment regimens and study design are likely to contribute to this variability, our results raise the possibility that differences in keratinocyte tumor DPD expression could also play a role in topical 5-FU treatment efficacy. The results of this pilot study support the value of a larger prospective study to investigate if DPD expression predicts clinical response of low-grade BCC and SCC to topical 5-FU. If true, then DPD IHC staining could be performed by pathology services to identify keratinocyte neoplasms that are more likely to respond favorably to topical 5-FU, reducing the uncertainty of treatment efficacy to this useful therapeutic option. None disclosed.