Can the Safe Surgical Margin Be Narrowed in Early-Stage... : Advances in Skin & Wound Care (2024)

INTRODUCTION

Among the nonmelanoma skin tumors, basal cell carcinoma (BCC) and squamous cell carcinoma are the most common;^1,2 BCCs constitute the majority of these tumors. Although BCCs can occur at any age, incidence increases with older age. The most common etiologic factors are sunlight and UV light exposure, fair skin, immunosuppression, radiotherapy, and genetic factors.³ In both men and women, 80% of nonmelanoma skin tumors develop in the face, head, and neck region.⁴

A BCC is diagnosed by histopathologic evaluation after excision of the lesion. There are several histologic subtypes of BCC: nodular, superficial, infiltrative, sclerosing, and mixed forms are the most common subtypes. All subtypes have peripheral palisaded hyperchromatic nuclei, narrow cytoplasm, and artifactual retraction of the stroma around the tumor islands,⁵ but the prognosis of each subtype can differ. Cutaneous tumors that are less than 2 cm in diameter are considered early-stage tumors.

Surgical excision with a safe margin is the most common and effective treatment for BCC. The size, localization, and histologic subtype of the tumor are important in determining the adequate surgical margin. Recommended surgical margins are 2 to 5 mm in low-risk BCCs and 5 to 15 mm in high-risk BCCs.⁶ Although BCCs grow slowly and rarely metastasize, they can cause extensive tissue destruction, especially on the face, if they are left untreated or are inadequately treated. A BCC may be considered high risk if it is located in the ear or in the middle of the face.³

It is difficult to reconstruct BCC-related defects in the facial region, especially around the natural orifices. Factors such as invasion of vital structures, histopathologic subtype, patient age, general condition, and cosmetic concerns all play an important role in determining the treatment modality. Depending on these conditions, it may be necessary to apply narrower surgical margins with complete tumor removal. Risk factors for inadequate surgical excision are tumor localization (ear, mid-face), tumor histology, and tumor size (>20 mm).^7,8

Previous research has aimed to understand relationships among BCC subtypes with dermoscopic appearance and clinical features.⁹ In the present study, the authors (1) examined the relationships among positive surgical margin and age, sex, tumor location, comorbid diseases, tumor size, and tumor thickness in BCC in the facial region and (2) investigated whether the surgical margin value can be narrowed in early-stage facial BCCs.

METHODS

Ethics

Ethics approval for this retrospective cross-sectional study was granted by the ethics committee of Bandırma Onyedi Eylül University Faculty of Medicine (approval no. 2022/4-5).

Participants

The study population included patients who underwent an operation in the face region at the study hospital between January 2018 and January 2022. Patients were included in the study if they were older than 18 years, they had at least 1 year of postoperative follow-up, and their pathology was reported as BCC. Pediatric patients, those whose pathology report did not indicate BCC, those who were diagnosed with incisional biopsy but were not operated on, patients with relapses or advanced tumors (tumor size >2 cm), and patients who were not followed up were excluded from the study.

Two researchers reviewed patient charts from their hospital files and recorded the following characteristics: age, sex, comorbid diseases (hypertension, diabetes mellitus [DM], cardiac diseases, and other), surgical notes, place of residence (rural or urban), pathology reports, tumor diameter and thickness, the condition of the surgical margin, tumor subtype, the surgical technique (primary or local flap repair), and tumor localization. Patient data were stored in a computer system that was accessed with the permission of the hospital management.

Operations were performed in the OR. Before beginning the operation, the lesion was examined under a surgical microscope, and the borders of the tumor were determined. Frozen sections were not used. Values reported as surgical margins represent the histologic margins made by the pathology department. Tumor localization was classified as forehead, periocular, periauricular, nasal (tip, alar, and dorsum), and cheek-malar (zygoma, nasolabial sulcus, temporal) regions.

Patient Grouping

The recorded subtypes of BCC were nodular, superficial, nodular-infiltrative, nodular-micronodular, nodular-sclerosing, infitrative, and micronodular. The authors categorized patients into three groups based on tumor subtype and prognosis: nodular and superficial subtypes with good prognosis (group 1); nodular-infiltrative, nodular-micronodular, and nodular-sclerosing subtypes with mixed prognosis (group 2); and infiltrative and micronodular subtypes with poor prognosis (group 3).

Histopathologic Examination

Specimens had previously been sliced into 4-μm-thick sections and stained with hematoxylin-eosin. For histopathologic examination, all hematoxylin-eosin-stained slides were reexamined (magnification ×400) and subtyped by a single pathologist with the permission of the department and in accordance with the World Health Organization 2018 Skin Tumors Classification.¹⁰ The largest diameter of the tumor and the closest distance to the surgical margin were measured and recorded. Tumor thickness was measured from the granular layer of the epidermis to the deepest point of the tumor. Only the longest diameter and the thickness were evaluated because the tumors were asymmetrical.

Statistical Analysis

The authors used SPSS for Windows (IBM Corp) for statistical analysis. Outcomes were presented as median and interquartile range (IQR) or mean and SD for numerical variables, and as frequency and percentage for categorical data. The normality of the data was evaluated with the Shapiro-Wilk test. The authors used one-way analysis of variance or the Kruskal-Wallis test for multiple comparisons and an independent-samples t test or a Mann-Whitney U test for pairwise comparisons (depending on their distribution). Categorical variables were compared via the χ² test or Fisher exact test. The statistical significance threshold was accepted as P < .05.

RESULTS

A total of 95 patients (47 men) with a mean age of 70.4 ± 11.4 years (range, 38–96 years) were included in the study. Regarding patient characteristics, 45.5% of the patients lived in rural areas and 54.5% lived in urban areas, 53.7% had hypertension, 13.7% had DM, 27.4% had cardiac diseases, and 23.2% had other comorbidities. When these data were compared with the positive surgical margin, there were no statistically significant differences (Table 1).

The most common tumor subtype was the nodular form (46.3%), followed by the nodular-micronodular type (24.2%); the superficial type was the least common subtype (4.2%). The positive surgical margin occurred at the highest rate (54.5%) in mixed forms.

Group 1 included 48 patients, group 2 included 32 patients, and group 3 included 15 patients. There were no statistically significant between-group differences in age, sex, tumor localization, comorbid diseases, place of residence, surgical technique, or tumor size (Table 2).

The mean surgical margin was 0.2 cm (IQR, 0.1–0.3 cm) in group 1, 0.1 cm (IQR, 0.05–0.2 cm) in group 2, and 0.1 cm (IQR, 0.05–0.3 cm) in group 3. In comparing these values, the surgical margin distance was greater in group 1 than in the other groups (P = .007; Table 3). Tumor thickness was 2 mm (IQR, 0.1–0.3 mm) in group 1, 3 mm (IQR, 2–4 mm) in group 2, and 3 mm (IQR, 2–5 mm) in group 3. The mean tumor thickness in group 1 was lower than those of the other groups (P = .020; Table 3). A total of 26 patients had tumors larger than 20 mm, and positive surgical margins were detected in only 2 of them.

In terms of tumor localization, BCCs were located in the nasal region in 33 patients, in the cheek and malar region in 23 patients, in the forehead in 12 patients, in the periauricular region in 15 patients, and in the periocular regions in 12 patients. Primary repair was performed in 43 patients after tumor excision, whereas local flap repair was performed in 52 patients. Surgical margins were reported as positive in five patients who underwent primary repair (11.6%; two in the nasal region, two in the periauricular, and one in the periocular) and in six patients who underwent local flap repair (11.5%; three in the nasal region, two in the cheek and malar region, and one in the frontal region). In comparing surgical techniques (primary vs local flap repair), the only factor that varied significantly between them was tumor localization (P < .001; Table 4).

DISCUSSION

Basal cell carcinoma is a common, slow-growing, locally infiltrative malignant tumor that rarely metastasizes and shows basaloid differentiation. Annual incidence varies by country but ranges between 0.07% and 1%.¹¹ Basal cell carcinoma develops from follicular and interfollicular keratinocyte stem cells^12,13 and is frequently seen in older adults. Roudier-Pujol et al¹⁴ reported that BCC in young patients is not more aggressive than in older patients.¹⁴ Studies have also reported that there are no differences between young and old patients in terms of histologic subtypes.^15,16

With aging, exposure to the sun and UV light increases cumulatively, and the immune system weakens. This may lead to increasing incidence of BCC with aging. The longer the sun exposure, the greater the risk of BCC. In addition, individuals who live in rural areas may have difficulty reaching the hospital, causing BCCs in this population to be diagnosed at a more advanced stage. However, fewer than half of the patients (45.5%) lived in rural areas in the present study. The reason for this may be that the rural areas in the study region are close to the downtown and the hospitals, and the region receives less sunlight than the southern parts of the country.

The histologically different subtypes of BCC have different prognostic features.¹¹ In the study by de Godoy et al,¹⁷ the nodular type was the most common, and the superficial type was the second most common.¹⁷ However, tumor persistence at the surgical margin was significantly higher in the high-risk group.¹⁷ In the study by Girardi et al,¹⁸ the most common subtypes were nodular and basosquamous forms, and the positive surgical margin was significantly higher in the aggressive forms.¹⁸ In the present study, the most common subtype was the nodular form (46.3%), followed by the nodular-micronodular type (24.2%); the superficial type was the least common subtype (4.2%). Unlike the literature, the positive surgical margin was found at the highest rate (54.5%) in mixed forms. All of the mixed forms had nodular components. The predominance of this subtype, which is an indicator of poor prognosis, in mixed forms of tumors may explain the high rate of positive surgical margin in the mixed group. Whereas the positive surgical margin rate was low in the good prognosis group, it was higher in the mixed group and highest in the poor prognosis group. In addition, there was a significant relationship in terms of the distance of the tumor to the surgical margin among the groups.

Depending on the characteristics of the tumor (size, location, recurrence, histologic subtype), ablative treatments, standard excision, or Mohs micrographic surgery (MMS) can be performed. Because ablative treatments do not have histopathologic control, they have a high risk of recurrence; this method may be preferred in low-risk BCCs. In unfavorable locations, or in the case of incompletely removed BCCs, recurrent BCCs, or large BCCs, MMS is preferred.¹⁹ Because these patients were not included in the present study, MMS was not performed. However, studies comparing standard excision and MMS for BCCs in the head and neck region have suggested that MMS should primarily be used for high-risk BCCs because of its high cost.^20,21 In the study by Smeets et al,²² although the recurrence rate after MMS was lower in facial BCCs compared with standard excision, the difference was not statistically significant.

One of the most important factors determining the positive surgical margin in BCC excision is the area of the intact tissue. In histopathologic analyzes, a tumor-free area of at least 1 mm is suitable microscopically for complete resection.¹⁸ However, in two different studies, a recurrence rate of 18% was found in facial BCCs with a 1- to 2-mm surgical margin.^23,24 In another study in which 134 facial BCCs were examined, the authors reported that the surgical margin of 1 to 3 mm was insufficient.²⁵ Nahhas et al²⁶ recommended a 4-mm surgical margin using standard excision for low-risk BCCs. Those authors also suggested having a surgical margin greater than 4 mm when using MMS for high-risk BCCs and noted that standard excision could be used as an alternative.²⁶ Dermatologic surgeons may prefer narrower surgical margins (<4 mm) in excision to reduce the defect area and avoid needing a flap or grafts.

Surgical margins of 4 mm cannot always be applied for excision in facial BCCs. Various studies have reported positivity of surgical margins after excision in facial BCCs at a rate of 16% to 18%.^23,27,28 The high rate of positive surgical margins for these excised BCCs may be due to the mixed histologic pattern of tumors. Even if the surgical margins are well-demarked macroscopically, subepidermal finger-like extensions of the tumor at the microscopic level may be the reason for the positive surgical margins. In such cases, MMS may be preferred.

In the present study, the surgical margin was 2 mm on average. This value is lower than those reported in the literature, and the positive surgical margin rate (11.57%) was lower as well. This may be due to the frequency of such surgeries in the authors’ clinic and the practice of using a microscope to determine the surgical margins preoperatively, especially with tumors that have irregular borders. Similarly, Quazi et al²⁹ reported that the excision margin could be 2 mm in well-demarked BCCs, and Thomas et al³⁰ found that it could be 3 mm. Herzum et al³¹ reported that BCC excision at 3 mm may be appropriate in the head and neck for small, well-defined, and nonaggressive BCCs with surgical cure rates of 100% and 1.5% recurrences. However, they recommended that 1- to 2-mm surgical margins should be performed for BCCs in difficult-to-treat areas because the surgical cure rate was only 93%.³¹

Tumor localization can affect decisions regarding which surgical technique to use, as indicated in the present study. Defects near the natural orifices and areas where the skin has more tension are difficult to reconstruct, which may lead to inadequate excision of the tumor. For example, the surgical margin positivity rate is 52% after BCC excision in the periocular region.³² Positive surgical margin rates may differ by tumor localization, but there is no consensus regarding what constitutes adequate surgical margin in each localization. In the present study, local flap repair was performed most often in the nasal and cheek and malar regions, whereas primary repair was performed most often in other regions.

Tumor localization is not the only factor that impacts treatment options for facial BCCs; surgical techniques may also vary based on the patient’s cosmetic concerns. Tumors with graft and/or flap repair are often large, and positive surgical margins may be seen more frequently. If the tumor is larger than 20 mm, this may be a risk factor for inadequate excision.⁷ However, in the present study, 26 patients had tumors that were larger than 20 mm, and positive surgical margins were detected in only 2 of them. Careful preoperative planning (dermoscopic or microscopic examination) can prevent inadequate excisions in large tumors. Inadequate excision in large tumors may be prevented by different surgeons performing the excision and reconstruction. Frozen section examination in suspicious cases can also significantly reduce the positivity of surgical margins.

Limitations

The fact that MMS was not perfomed in some BCC tumor localizations where it is recommended may be a limitation of this study. Another limitation is that advanced-stage tumors were not included in the study.

CONCLUSIONS

Different histologic subtypes of BCC show different prognostic features. Tumor thickness, tumor localization, and adequate surgical margins at the excision are important factors for the prevention of recurrences and regional tumor control. To prevent positive surgical margins, surgeons should individually plan the treatment of each patient according to the tumor characteristics and the patient’s risk factors. With further research, adequate surgical margin values may change in early-stage facial BCCs and will standardize according to tumor localization. Preoperative macroscopic evaluation of the tumor margins with a surgical microscope may decrease the positive surgical margin rates. The surgical margin, which the literature recommends be approximately 4 or 5 mm, could potentially be narrowed to 2 mm in early-stage facial BCCs.

REFERENCES