Characteristics of Mixed Type Basal Cell Carcinoma in Comparison to Other BCC Subtypes.

BACKGROUND: There are limited data exploring the characteristics of mixed type basal cell carcinoma (BCC).
OBJECTIVES: To explore different characteristics of mixed type BCC.
DESIGN: Cross sectional study.
MATERIALS AND METHODS: 825 patients with BCC enrolled in this study.
RESULTS: Among 825 patients, 512 (62%) were male. Three hundred and fifty five (43%) presented with nodular subtype, 267 (32.4%) with mixed subtype, 25 with superficial and the 178 remaining presented with other subtypes. Four hundred and eighty three (58.6%) of the lesions were on the face, 243 (29.5%) on scalp, 52 (6.3%) on ears, 20 (2.4%) on neck, 15 (1.8%) on trunk and 12 (1.4%) on extremities. Anatomic distribution of mixed type was as follows: 137 on face, (51.4%), 100 (37.3%) on scalp, 19 (7%) on ear, 6 (2.1%) on neck, 4 (1.5%) extremity and 1 (0.7%) on trunk, which the difference from non mixed types was statistically significant (P = 0.002). The mean diameter of the mixed types and non mixed type BCCs were significantly different (2.7 ± 2.1 cm vs. 2.2 ± 1.6 cm; P = 0.01. The prevalence of necrosis in mixed type BCC was two times higher than non mixed type BCCs (OR = 2.3, CI 95% 1.3-3.9, P = 0.001). The most frequent combined subtypes were nodular-infiltrative (P < 0.001).
CONCLUSION: Mixed type BCC has differences with other BCC subtypes in anatomical distribution and tumor diameter. Indeed, mixed type BCCs are frequently composed of aggressive subtypes than nonaggressive subtypes.

What was known?

There are a little data available on characteristics of BCC and its different subtypes specially mixed type.

Introduction

Skin cancer is the most common cancer in countries with predominantly fair-skinned populations, and basal cell carcinoma (BCC) is the most common type of skin cancer in Caucasians, usually occurring on sun-exposed areas.[12] Its annual incidence is estimated to be 2.75 million new cases worldwide[34] with a projected annual increase of 10%, which can be due to sun exposure and increased outdoor activities.[56] Despite the low mortality rate of the tumor, BCC can grow locally leading to extensive tissue damage. Considering the high prevalence of BCC on head and neck, the mentioned pattern of growth can cause high morbidity and impose high burden of disease.[378] There are various methods for BCC treatment including cryotherapy, curettage and electrodesiccation, intralesional immunomodulator (alpha interferon), photodynamic therapy, radiotherapy, surgical excision, topical chemotherapy (5-fluorouracil cream or solution) and topical immunomodulator (imiquimod 5% cream), and Mohs microscopically controlled surgery.[910] The histologic tumor subtype is often a factor used by the clinician to choose the appropriate method for treating the tumor, in which more aggressive types need more aggressive treatment.[10] There are several subtypes of BCC with the nodular subtype being most common. However, the infiltrating, micronodular, multifocal, superficial, morphoeiform and mixed histopathological patterns are more aggressive and prone to recurrences.[31112]

The term mixed BCC refers to BCCs with presence of two different subtypes of the tumor in one sample e.g., superficial BCC in dermis and sclerosing type in deep dermis. The reported incidence of mixed subtype varies between 11% and 39% according to published literature.[131415]

Mixed BCC is important for many reasons. According to the literature, different BCC subtypes occur on different anatomic sites raising the idea that different subtypes might have different causes and pathogenesis. Studying the different subtypes of BCC can improve our knowledge of each subtype and also the main tumor.[16] Also, there is evidence supporting the idea in which mixed BCC subtype may be associated with tumoral recurrence and with accordance to the fact that different BCC subtypes need specific treatment methods exploring the characteristics of the mixed type may lead to find or choose a more effective treatment method.[17] According to lack of relevant data considering the characteristics of different BCC subtypes and the probable differences between them, the present study is designed to explore the characteristics of mixed type BCC and compare them with other BCC subtypes in Iranian population.

Materials and Methods

This is a retrospective study of 825 patients with BCC in Razi Dermatology Center, Tehran, Iran. Patients with recurrent tumors were also included but recurrences were not counted as separate patients. All the skin colors were types III and IV of Fitzpatrick Classification Scale. The samples were included on the basis of the histopathological diagnosis of BCC, which was confirmed by two dermatopathologists.

The classifications of tumor subtypes were done using World Health Organization (WHO) classification system. Informed consent was obtained from all patients. Demographic data with tumor location were also obtained from all patients and their medical records.

Statistical analysis

The results are expressed as mean ± SD. Statistical analysis was performed using SPSS version 16.0.1 (SPSS Inc., Chicago, IL, U.S.A.). The statistical differences between proportions were determined by χ2 analysis. Numerical data were evaluated using analysis of variance, followed by Tukey's post hoc test. P < 0.05 was considered as significant.

Results

Among 825 patients, 512 (62%) of them were male and 313 (38%) were female with mean age of 63 ± 12.1 vs. 60.9 ± 13. The mean age of the patients with mixed type was 62.23 ± 12.6 vs. 62.32 ± 12.4 in non mixed type group (P > 0.5). Among 825 patients, 355 (43%) presented with nodular subtype, 267 (32.4%) with mixed subtype, 25 with superficial and the 178 remaining presented with other subtypes, the details are summarized in Table 1. Indeed, 483 (58.6%) of the lesions were on the face, 243 (29.5%) on scalp, 52 (6.3%) on ears, 20 (2.4%) on neck, 15 (1.8%) on trunk and 12 (1.4%) on extremities, showing that 96.8% of the lesions were on head and neck of the patients. Anatomic distribution of mixed type was as follows: 137 on face, (51.4%), 100 (37.3%) on scalp, 19 (7%) on ear, 6 (2.1%) on neck, 4 (1.5%) extremity and 1 (0.7%) on trunk, which the difference from non mixed types was statistically significant (P = 0.002) [Table 2]. The anatomic distribution of mixed types was not different between male and female. The mean diameter of the mixed types and non mixed type BCCs were 2.7 ± 2.1 cm vs. 2.2 ± 1.6 cm, which the difference was significant (P = 0.01). According to results the prevalence of necrosis in mixed type BCC was two times higher than non mixed type BCCs (OR = 2.3, CI 95% 1.3-3.9, P = 0.001).

Table 1

Frequency of different BCC subtypes

Table 2

Anatomical site of mixed type vs. non mixed type BCC

The frequency of different subtypes in mixed types is shown in Table 3. As seen in Table 3, the most frequent combined subtypes were nodular-infiltrative, nodular-superficial, nodular-micronodular and nodular-adenoid, respectively (P < 0.001). There was no significant difference between different mixed type BCCs and anatomic or gender distribution. Figures 1 and 2 are clinical and pathological images of mixed and non mixed type BCCs.

Table 3

Different subtypes in mixed type BCC

Figure 1

(a) Ulcerated micronodular type BCC on the nasal ala (b) Ulcerated mixed type BCC with enrolled margin

Figure 2

(a) Micronodular BCC (H and E, × 0) (b) Pigmented mixed nodular and adenoid BCC (H and E, ×40)

Discussion

Basal cell carcinoma is the most frequent cancer in humans.[1819] It presents with different pathologic features and has specific anatomical site distribution.[202122] One of the frequent histopathologic features of the tumor is mixed type BCC.

Despite the high frequency of the tumor there are little studies exploring the characteristics of different subtypes of BCC and the probable differences between them. There are different treatment methods for BCC tumors ranging from medical to surgical therapy in which tumor histopathologic pattern is one of the most determinant factors in choosing the suitable treatment method.[1723] According to our results most of the mixed type BCCs occurs on face and scalp as other BCC subtypes, but the results also show that mixed type BCC has more tendency to occur on scalp than face but other BCC subtypes more frequently occur on face than scalp. Our results reveal that most of the mixed type BCCs has larger diameter than other subtypes (comparing the tumors’ largest diameters). Indeed, mixed type BCCs undergoes excisional biopsy more frequent than other BCC subtypes which is in accordance with the former result showing the greater mean of largest diameters of mixed type BCCs than other subtypes. Also the data show that necrosis has higher prevalence in mixed type than other BCC subtypes.

Exploring the pathologic features of the mixed type reveals that most of the mixed type BCCs has a nodular component. This can be logical because of the fact that nodular BCC is the most common subtype of BCC.[514]

According to literature, mixed and infiltrative types of BCC are considered as aggressive forms of the tumor.[24] Considering the high prevalence of nodular-infiltrative pattern in our cases of mixed type BCC and also greater diameter of mixed type BCCs than other BCC subtypes the data can be in accordance with the previous data discussing the risk of BCC recurrence in mixed type BCC although we cannot directly conclude this with our results.[1013] Our study is a cross sectional study considering the different characteristics of mixed type BCC and compare the findings with other BCC subtypes. Here we reported some differences but the impact of them on the tumors behavior and treatment outcome cannot be assessed with our results. Further studies as suggested to determine the effects of different BCC subtypes on the patients’ outcome and also behavior of each subtype.

In light of the fact that there are a little data available on characteristics of BCC and its different subtypes specially mixed type, the present study may provide some new and useful data about mixed type BCC, leading to better understanding and management of the tumor, although more studies are recommended.

What is new?

We introduced some characteristics of mixed type BCC and its differences from other BCC subtypes.