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Division of Plastic Surgery, Department of Surgery, King Saud University Medical City, King Saud University and Department of Plastic Surgery & Burn Unit, King Saud Medical City, Riyadh, Saudi Arabia
Hand basal cell carcinoma is a rare and complex disorder. Due to the hand's anatomical features, managing hand BCC is challenging. Therefore, we have conducted this systematic review to investigate various clinical characteristics, investigations, and treatment options related to hand BCC. Furthermore, a meta-analysis was used to provide pooled recurrence rates.
Methods
We conducted this review per the International Prospective Register of Systematic Reviews (PROSPERO) guidelines. This study performed a systematic literature review in February 2022 using the following electronic databases: Cochrane, MEDLINE, and EMBASE. Key terms include hand basal cell carcinoma, basal cell carcinoma, management, outcome, and recurrence. We evaluated articles according to predefined quality criteria.
Results
The study included 9725 patients and 51 published articles. A total of 35 case reports, 2 case series, 1 prospective study, and the remaining retrospective studies were evaluated. An asymptomatic skin lesion was the main complaint. In 10 studies, Moh surgery was the most frequently used treatment method. In the seven studies included in the meta-analysis, the overall incidence rate of recurrence among the included patients was 1.49 cases per year.
Conclusion
The optimal extent of surgical treatment is still controversial, though an early biopsy can help identify lesions at an early stage. It is the first study to provide occurrence rates based on a meta-analysis. Developing treatment guidelines for BCC of the hand will be the focus of future research.
Although patients' cumulative exposure to ultraviolet light is a significant risk factor for BCC, exposure to ultraviolet light alone does not precisely predict the probability of developing BCC at a specific site.
It is believed that BCC originates from pluripotential epithelial cells in the deep layers of the epidermis and hair follicles, and it tends to occur only in areas where both hair follicles and sebaceous glands are present.
Moreover, when BCC occurs proximally to the upper extremity, it usually presents as classical BCC. On the other hand, acral BCC presents as erythematous skin plaques with scaling or exophytic tumors with the absence of the classical pearly appearance and telangiectasia. The diagnosis of a suspected BCC is made through either a shave biopsy or a punch biopsy.
There are several histological types of BCC, including superficial and nodular, and types with high recurrence rates, such as micronodular, infiltrative, metatypical, and morpheaform patterns.
Treatment options for BCC of the hand vary; they include both surgical and nonsurgical treatment options. Nonsurgical options include topical immunomodulators (e.g., imiquimod), cryotherapy, radiation, photodynamic therapy, intralesional treatment (e.g., 5-fluorouracil), curettage, and electrodesiccation.
Although the tumor management of the hand surgically requires special considerations, surgical excision is the favored treatment method for BCC. Reconstruction of the hand is challenging as the surgeon must consider protecting both the hand's function and appearance. Margins differ depending on the grade and the size of the lesion. The recommended margins for smaller or low-grade lesions are 4 mm, while larger, high-grade lesions require margins of at least 6 mm.
The literature lacks comprehensive systematic reviews and meta-analyses of the literature regarding the presentation, optimal management, and outcomes of hand BCC. To the authors' knowledge, this is the first systematic review that assesses a variety of clinical characteristics, investigations, and treatment options in the literature for hand BCC. We have additionally presented pooled recurrence rates based on a meta-analysis.
Methods & materials
Literature review
We designed this systematic review using Cochrane review methods and utilized preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines.
The ethical approval was waived due to the type of study, and the review was carried out in compliance with the Helsinki Declaration. In February 2022, a systematic search was conducted in the following databases: MEDLINE, Cochrane, and EMBASE. The keywords used were the following: basal cell carcinoma, BCC, hand, nail, thumb, subungual, treatment, wide excision, local excision, amputation, conservative therapy, recurrence, and outcome. The search results included studies published without time frame limitations.
Study selection
Four reviewers evaluated the titles and abstracts of the gathered articles that were included, and the included studies were selected for a comprehensive review. If the title or abstract did not provide enough information about the article's content, the full text was examined. A fifth independent reviewer reviewed all articles selected by both groups. The inclusion criteria of the study review are as follows: (1) articles published from inception to February 2022; (2) conveyed a randomized controlled trial; prospective or retrospective cohort/comparative, case-control, case series, or case reports; (3) adult and pediatric patients; (4) patients with hand BCC (volar, dorsal, and nail unit); (5) those that reported outcomes of interest for the clinical questions proposed; and (6) all languages were included in the review. The studies that were eliminated for satisfying the exclusion criteria were as follows: (1) improper method (illustrated by a meta-analysis/systematic review, economic analysis, animal study, cadaver study, narrative review, or editorial); (2) conveyed no outcomes of interest; and (3) articles that did not include patients with hand BCC.
Screening and data extraction
Four independent reviewers screened full-text articles using the Rayyan search engine,
and data were collected. Any disagreement was resolved by a fifth reviewer. General demographic data were gathered, such as authors' last names, country, study design, sample size, patients' age, sex, race, main presenting symptom, history of skin cancer, immune status, location of lesion, morphology, tumor invasion, treatment modality, follow-up timeframe, diagnosis, and recurrence/cure rates, which were further analyzed for meta-analysis. The level of evidence was assigned to each of the included articles, following the criteria described in the American Society of Plastic Surgeons' rating levels of evidence and grading recommendations.
We used the methodological index for the nonrandomized studies (MINORS) assessment tool. The instrument is a validated 12-item instrument designed to assess the quality of nonrandomized surgical studies.
Two reviewers evaluated the risk of bias in all included studies using the MINORS criteria, and a third reviewer reviewed the assessments. The methodological quality and synthesis of case series and case reports were assessed using the methodological quality and synthesis of case series and case report assessment tool.
A total of eight questions are divided into four main domains: selection, ascertainment, causality, and reporting. For both reviewers, the final answers were identical.
Statistical analysis
In the data analysis stage, the pooled estimates were calculated based on studies with at least 10 patients and available follow-up periods (years). The overall proportion of patients with BCC was computed according to the meta-analysis of single proportions. The incidence rate of recurrence was collected from each study, and a pooled outcome was estimated using person-time as time (years), the rate of recurrence as an event, and the total number of patients with BCC as the overall number. We calculated the overall incidence rate using log transformation and the inverse variance method, and continuity correction was applied for studies with zero events. Random-effects models were applied for all the analytical approaches. Heterogeneity assessment was carried out using the I2 test. To assess the sources of heterogeneity, we carried out a subgroup analysis based on the treatment modality and sensitivity analysis.
Results
Characteristics of the included studies
A total of 3081 articles were found in this systematic review, including 924 articles from EMBASE, 1540 articles from MEDLINE, and 617 articles from the Cochrane library. The number of articles for review remained at 2985 after removing duplicates. Initially, we were able to retrieve 110 full-text publications. However, after applying the previously defined inclusion and exclusion criteria, 51 studies were included in the qualitative synthesis published between 2006 and 2020 (Fig. 1). The following reasons prompted the exclusion of 59 articles: improper methods (systematic review, review article, and letter to editor), n = 12, no outcome of interest (n = 19), the full text could not be located (n = 14), the specific location of BCC was not stated (n = 12), included non-hand BCC patients (n = 2). Thirty-five studies were case reports,
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
and the remaining studies were published in North America. A total of 9725 patients were included (760 patients had BCC). More details about the characteristics of studies and patients are provided in Table 1.
Fig. 1The PRISMA flowchart for systematic review. The process of selecting the included studies.
Gender distribution was based on the total number of patients with BCC; CR: case report; CS: case series; R: retrospective cohort; P: prospective cohort; M: male; F: female.
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
Gender distribution was based on the total number of patients with BCC; CR: case report; CS: case series; R: retrospective cohort; P: prospective cohort; M: male; F: female.
The mean patient's age was 62.8 years old (a range between 1.16 to 90 years old). Two studies were reported in the pediatric age groups in 1.16 and 5.56 years old. The main presenting complaint in ten of the articles was an asymptomatic skin lesion, 3 were mass-like, 3 were nail deformities, 4 were nonhealing ulcers, 14 were ulcerated lesions, and 15 did not mention anything. In terms of race, 20 of the articles were Caucasians, and only 1 study reported an Asian patient.
The clinical characteristics are listed in Table 2. Nail involvement was reported in 41 studies, of which the nails were involved among the patients in 16 studies (39%).
and the lesions were approximately equally distributed (33 and 31 lesions in the right and left hands, respectively). Metastasis was positive in a case report,
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
In the meta-analysis, seven studies were included. A total of 2051 patients were included, of whom 652 patients had BCC with an overall pooled proportion of 32.24% (95%CI, 14.37% to 57.44%, Fig. 2). There was a significant heterogeneity among studies (I2 = 98.7%, p < 0.0001).
Fig. 2A forest plot shows the rate of BCC among the included patients.
The overall incidence rate of recurrence among the included patients was 1.49 cases per year (95%CI, 0.58 to 3.82, Fig. 2). The heterogeneity among studies was significant (I2 = 83.2%, p < 0.0001). However, studies which recruited patients who underwent surgical excision showed no significant heterogeneity in the incidence rate of recurrence (incidence = 1.48 case-years, 95%CI, 0.86 to 2.55, I2 = 0%, p=0.56). Additionally, subgroup differences were significant based on the treatment provided (Chi2= 35.66, p < 0.0001). Heterogeneity analysis for other treatment modalities was not conducted because these treatment approaches were performed in a single study (Fig. 3).
Fig. 3A forest plot shows the incidence rate of BCC recurrence among patients treated by four modalities.
To further investigate the sources of heterogeneity, we implemented an influence analysis (sensitivity analysis) by omitting each included study at once. The study of Fischbach et al. had the largest influence effect size.
Following the exclusion of such a study, the overall heterogeneity dropped to 1.2%, and the overall incidence rate was 1.28 cases per year (95%CI, 0.76 to 2.14, Fig. 4). The exclusion of other studies did not influence the heterogeneity analysis.
Fig. 4A forest plot shows the results of the influence analysis.
The authors evaluated the case reports and case series included in the study. Bias was evaluated separately and concurrently by two reviewers. We used a methodological quality assessment tool based on 8 components that are divided into 4 domains: selection, ascertainment, causation, and reporting (Table 3).
The findings of both reviewers were the same, regardless of whether the material seemed biased. MINORs were at least 52,84% in all retrospective and prospective studies considered. There was 1 comparative study, and it ranked a total score of 24. Eleven noncomparative studies had an average score of 8.45 (range 12–4). The results are summarized in Tables 4 and 5.
Table 3Qualitative assessment of the included studies.
Domain For Evaluating the Methodological Quality of Case Reports and Case Series
Selection: [question 1]. Does the patient(s) represent(s) the whole experience of the investigator (center) or is the selection method unclear to the extent that other patients with similar presentations may not have been reported?.
Ascertainment: [question 2]. Was the exposure adequately ascertained? [question 3]. Was the outcome adequately ascertained?.
Causality: [question 4]. Were other alternative causes that may explain the observation ruled out? [question 5]. Was there a challenge/rechallenge phenomenon? [question 6]. Was there a dose-response effect? [question 7]. Was follow-up long enough for outcomes to occur?.
Reporting: [8] Is the case(s) described with sufficient details to allow other investigators to replicate the research or to allow practitioners to make inferences related to their own practice?.
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
Although basal cell carcinoma accounts for 80% of all cutaneous malignancies, squamous cell carcinoma occurs more frequently on the hand when compared to basal cell carcinoma.
Furthermore, the dorsum of the hand is considered a frequently sun-exposed area. However, hand BCC occurrences are relatively uncommon when compared to the head and neck.
When taking skin surface into account, BCC of the dorsum of the hand tends to have roughly the same frequency as other body sites—excluding the face and neck, where BCC is most common.
To the best of the authors' knowledge, this is the first systematic review that examines a variety of clinical characteristics, investigations, and treatment options available in the literature for hand BCC. Furthermore, we have presented pooled recurrence rates based on a meta-analysis. The overall rate of hand BCC recurrence was 1.49 cases per year. However, after excluding cases treated with radiotherapy as a single modality, which accounts for the highest recurrence rate among the included studies,
the overall incidence rate will be 1.28 cases per year, with almost all patients managed surgically. A systematic review published in 2009 investigated the clearance rate of BCC after 5 years of follow-up and found a 99% clearance rate with Mohs micrographic surgery, 91–95% with wide local excision, and radiotherapy associated with a lower clearance rate of 90%. In spite of its higher recurrence rate than surgical excision, radiotherapy still provides better cosmetic outcomes. It must be considered as one of the first nonsurgical choices in patients who cannot survive surgeries.
A recent RCT compared the combination of curettage and cryosurgery versus curettage and electrodesiccation in managing sBCC. At 12 months of follow-up, only one patient experienced a recurrence in the cryosurgery group. Both techniques had good scar results by the end of the study. Nonetheless, the short follow-up period might not reflect reality, and more studies are needed to investigate the combination of different modalities.
Prospective clinical trial comparing curettage and cryosurgery to curettage and electrodesiccation in the management of minimally invasive basal and squamous cell carcinomas.
In these studies, 34 out of 2051 patients experienced fingernail involvement with variable morphological features including ulcerative, longitudinal plaque, or onychodystrophy.
Many of the reported studies found initial difficulties in obtaining the correct diagnosis of BCC due to the wide variety of lesions and malignancies that can arise from the hand with similar morphological features, including glomus tumor,
These findings highlight the importance of performing biopsies in cases with uncertain diagnoses or failure of treatments to detect misdiagnosis. Almost all patients with nail involvement were managed surgically by MSS (43%), simple excision (31%), or amputation (19%). None of the patients experienced recurrence except for a single case reported ten months post-operation. The author suggested a minimal clearance margin of 0.5 mm to be responsible for the recurrence rather than the failure of the modality.
Mohs micrographic surgery has shown superiority in the clearance rate and the advantages in preserving the adjacent soft tissue with high accuracy. Therefore, the integrity of sophisticated hand function is preserved. The need for soft-tissue coverage post-excision is variable according to the lesion size and site. Several studies reported the successful usage of FTSG with optimum function restoration and good cosmetic outcomes.
However, in most cases, where Mohs micrographic surgery has been used, they found no indication for autologous reconstruction and managed the case by dressing and healing subsequently by secondary intention.
To our knowledge, this systematic review and meta-analysis are the first to investigate the current management options and outcomes of BCC in the hand. The strengths of this systematic review and meta-analysis are that it is noncommercial, has strict inclusion and exclusion criteria, and was reported in line with the PRISMA criteria with no deviations from the protocol. The methodological quality and synthesis of all the studies were assessed for bias, and all had MINORS above 70%. This study analyzed the most recent hand BCC studies at the time of writing, providing the most comprehensive data pool available. Nonetheless, our study has several limitations. First, most of our results were based on case reports, which comprised most of the studies included in this systematic review, with the weakest evidence level. Second, most of the studies included in this study were from North America and Europe; hence, the results may not be generalizable. Third, not all studies included in this systematic review are recent, mainly due to the
Gender distribution was based on the total number of patients with BCC; CR: case report; CS: case series; R: retrospective cohort; P: prospective cohort; M: male; F: female.
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