Management and Clinico-Pathologic Aspects of Non-Melanoma Skin Cancer of the Head and Neck: A Retrospective Institutional Based Study at the Egyptian National Cancer Institute ()
1. Introduction
Non-melanoma skin cancer (NMSC) is the most common malignancy among Caucasians. NMSC principally comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), but includes a host of rarer skin tumors [1]. According to The National Cancer Registry in Egypt based on Data of 40,477 patients collected from Tanta Cancer Center retrospectively to form the largest population-based cancer registry in Egypt covering a period of 9 years, skin cancer incidence was calculated as 3.1% of all cancers in both sexes and 3.8% of all cancers in males based on population of Gharbia (as an indicator for rates in Egypt) and based on number of cases of each cancer type there [2]. In the Egyptian population, over 60% of NMSC could be attributed to sun exposure and approximately 45% to skin color [3]. More specifically the incidence of NMSC was addressed at the National Population-Based Cancer Registry Program (2008-2011) as 1.35% of all cancers in males and 1.24% of all cancers in females [4]. In settings such as developing countries where Moh’s Micrographic Surgery is not readily available, prediction of NMSC aggressive lesions based on preoperative information (age, immunosuppression status, and location) is critical not only for surgical planning but also for reducing recurrence risk by treating the lesion with sufficiently adequate margins. Several studies have attempted to create a risk scale or model for assessing preoperative risk for aggressive NMSCs [5] [6] [7] [8]. In Egypt, few studies focused on NMSC, mostly with a limited number of patients and not specific to NMSCHN and not addressing many prognostic factors highlighted and evaluated in this study [9] [10] [11] [12]. In other parts of the world, with almost similar climate to Egypt, skin cancer is a common cancer [13], with increasing incidence of SCC and Basosquamous carcinoma (BSC) [14]. This study will focus on Egyptian patients with non-melanoma skin cancer of the head and neck (NMSCHN) who presented, diagnosed and managed at the National Cancer Institute—Cairo University—Egypt.
2. Materials and Methods
A retrospective study where all patients’ data with non-melanoma skin cancer of the head and neck (NMSCHN) diagnosed, admitted and managed at the National Cancer Institute—Cairo University—Egypt in the period from January 2008 to December 2012 were documented and analyzed regarding patients’ characteristics (age and sex), tumor characteristics (anatomical site, T stage and number of lesions), histopathology (type and grade), treatment modality (surgery ± adjuvant treatment or no interference), safety margin status (positive, close or negative), type of reconstruction and type of flap used, complications and recurrence(s) during a follow-up period ranging from 1 to 84 months with a mean follow-up of 6 months. Recurrence and Disease-free survival will be correlated statistically with different parameters.
2.1. Exclusion Criteria
· Patients with NMSCHN who were managed outside our institute and were just referred for follow-up or for consultation.
· Patients with Xeroderma pigmentosum.
· Patients with melanoma skin cancer by histopathology.
2.2. Statistical Method
Demographic data and survival outcome will be analyzed using SPSS statistical package version 20. Relations between qualitative data will be done using Chi-square test or Fisher’s exact test. Moreover, survival analyses will be done using Kaplan Meier’s method and Comparison between survival curves will be done using log-rank test. A p-value less than 0.05 will be considered significant.
3. Results
Two hundred patients with NMSCHN were involved in this retrospective study in the period from January 2008 to December 2012.
3.1. Patients’ Characteristics
· Age: The age of the patients ranged between 5 and 90 years with the peak incidence in the sixth decade of life. 15.5% of patients were below or equal to the age of 50 while 84.5% were 51 years old or more (Table 1).
· Sex: Male patients constituted 58.5% (117/200) of cases while females constituted 41.5% (83/200). Male to female ratio was about 1.4:1 (Table 2).
3.2. Tumor Characteristics
· Anatomical distribution of lesions: The main site affected was the scalp 27.5% (55/200), followed by the periorbital region 13% (26/200), while the cheek and nose were equally affected 12.5% (25/200) each. Two patients with BCC showed multiple lesions in different sites 1% (2/200) (Table 3).
· T Stage: The majority of cases were T1 representing 52% of all cases (104/200) and T4 representing 4% (8/200) with tumor invasion to parotid gland and eye globe (Table 4).
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Table 1. Age distribution of patients with NMSCHN.
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Table 2. Sex distribution of patients with NMSCHN.
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Table 3. Anatomical site distribution of NMSCHN lesions.
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Table 4. Distribution of NMSCHN lesions according to T stage.
· Number of Lesions: 94% (188/200) of patients presented with a single lesion, 1% (2/200) of patients presented with 2 lesions and 5% (10/200) with multiple lesions. 12 patients presented with two and more lesions where 8 of them BCC (two of them in different sites), 2 SCC and 2 were BSCC patients (Table 5).
3.3. Tumor Histopathology: (Tables 6-8)
All lesions were pathologically examined preoperatively and postoperatively to confirm the diagnosis and determine the margin status. BCC was detected in 72.5% (145/200) of patients, SCC in and basosquamous were detected in 21% (42/200) and 6% (12/200) of patients, respectively (Table 6). The most common type of BCC was the nodular type representing 79% (113/200) of cases (Table 7). The most common grade among the fifty four patients with Squamous Cell Carcinoma (SCC) and Basosquamous Carcinoma (BSC) was grade II, moderately differentiated tumors represented 61.1% (33/54) of cases (Table 8).
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Table 5. Distribution of patients with NMSCHN according to the number of Lesions per patient.
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Table 6. Tumor histopathology of NMSCHN among the study population.
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Table 7. Clinico-pathologic types of BCC.
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Table 8. Histopathological Grades of Squamous Cell Carcinoma (SCC) and Basosquamous Carcinoma (BSC).
3.4. Treatment Modality: (Table 9)
Surgery was the only treatment modality in 93% (186/200) of patients, surgery followed by post-operative radiotherapy (PORT) in 2% (4/200) of patients, they had positive margins and were not candidates for re-excision because of reconstruction and proximity to the eye. One patient (0.5%) developed metastatic SCC and received adjuvant chemotherapy 3% (6/200) of patients developed local recurrence followed by lung metastasis they underwent surgical excision followed by radiotherapy then chemotherapy. Meanwhile, 3 patients with BCC (1.5%) received no treatment because they were locally advanced, elderly with co-morbidities and beyond treatment.
3.5. Safety Margin Status: (Table 10)
Peripheral margin control guided by intraoperative frozen section analysis (IFSA) was not used in all patients but most of them. Postoperative Histopathological examination of all surgically excised specimens was done (except for four patients where SM was not assigned) for histopathological confirmation of tumor type and to detect adequacy of the safety margins where all specimens’ margins were oriented by sutures. Margins of surgical excision were negative in 150 (76.5%), positive in 41 (20.9%) and close in 5 (2.6%) of postoperative specimens.
3.6. Closure of the Defect and Type of Reconstruction: (Table 11 & Table 12)
Most of the study population underwent reconstruction with local flaps only 126/197 (63.9%), in 14.7% of patients (29/197) primary closure only was successfully achieved. Among patients who underwent surgical excision the method
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Table 9. Treatment modality in patients with NMSCHN.
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Table 10. Safety margin status in postoperative pathologically examined specimens.
of defect closure was not assigned in only one patient 1/197 (0.5%) due to inadequate patient operative documentation. Rotational flaps (Figures 4-6) were the most commonly used type of flaps for the reconstruction of post-excision defects in this study (28.3%) followed by advancement flaps (27%) (Figure 1) then forehead flaps (12.1%) (Figure 3).
3.7. Distribution of BCC and SCC in Relation to Different Factors
Regarding sex, number of lesions, treatment modality, occurrence of complications and safety margin status no statistically significance was detected in relation to the histopathological type of NMSCHN either BCC or SCC (after exclusion of other histopathological types) (Table 13).
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Table 11. Methods used for closure of the defects following surgical excision of NMSCHN.
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Table 12. Types of local flaps used for reconstruction following surgical excision of NMSCHN (Figures 1-7).
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Figure 1. Advancement cheek flap for left cheek BCC.
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Figure 2. Bilobed flap for BCC of the nose.
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Figure 3. Large SCC of the nose with forehead flap to close the defect.
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Figure 4. SCC of the occipital region with WLE and closure of the defect with rotational scalp flap.
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Figure 5. BCC below the right lower eye lid WLE was done with rotational flap.
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Figure 6. Rotational flap for right nasal BCC.
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Figure 7. Full thickness (Wolfe) graft from the skin of the arm after WLE of BCC of the nose.
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Table 13. Distribution of BCC and SCC in relation to different factors and its significance.
3.8. Recurrence (Locoregional/Distant): (Table 14)
Fifty patients developed loco-regional recurrence. Out of the 50 patients who developed loco-regional recurrences, 45 developed single recurrence and 5 developed repeated recurrences. 9 patients developed regional lymph nodes
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Table 14. Correlation between different factors and recurrence among NMSCHN patients.
metastasis. 6 patients of them were SCC and 3 patients were BSC. Those patients underwent neck dissection. During follow-up 6 SCC, patients developed pulmonary metastasis.
Many independent prognostic factors were found to significantly affect the recurrence rate among patients with NMSCHN. Patients aged more than 50 years old (p-value = 0.18), patients with multiple lesions (p-value = 0.007), patients with high grade of SCC or BSC (p-value = 0.008), patients with positive and close margins (p-value = 0.001), patients subjected to surgery + adjuvant therapy (p-value = 0.001) and patients who showed PO complications (p-value = 0.051), all those, showed significantly higher recurrence rate in relation to the rest of the study population. Other factors as T stage, sex of patients and BCC vs. BSC pathology didn’t show a significant increase in recurrence rate among the study population (Table 14).
3.9. Disease-Free Survival (DFS): (Table 15)
Disease free survival ranged from 10.5 to 29.5 months with a median of 20 months. Regarding age, sex, T stage, treatment modality, occurrence of complications, histopathology (BCC vs. SCC) and safety margins; none of those factors showed a statistically significant correlation with Disease-free Survival (DFS).
4. Discussion
To our knowledge, this study is by far the largest one in Egypt addressing non-melanoma skin cancer of the head and neck (NMSCHN), regarding the number of patients and the period of follow up which extended up to 84 months. The incidence of non-melanoma skin cancer is still rising worldwide [15], this increase can be, in part, attributed to the increase in the elderly population, in addition, many patients develop more than one non-melanoma skin cancer after the first one [16]. In this study, patients over 50 years old represented 84.5% of the study population (mean 60, 6 years with the peak incidence in the sixth decade) in whom recurrence rate was significantly higher (p-value = 0.18), similarly some studies on NMSC detected a peak incidence in the sixth decade of life [10] [11] [17] [18], others in the seventh decade [8] [9] [13] [19] [20]. Male predominance was observed in this study as well as other studies [9] [11] [14] [19] [21], on the other hand, other studies of NMSC showed female predominance [10] [13] [17] [20]. The male sex predilection of skin cancer in Egypt is explained by the fact that men represent the main workforce (outdoor work) with more risk for UV exposure than women [22]. NMSC most commonly occur in the head and neck region [1] [10] [11] [13] [21] [23] [24] [25], and according to this study the scalp, nose and cheek are the most common anatomic sites for the occurrence of NMSCHN, according to Mahmoud et al., 2006 the cheek and nose [10], according to Rhee et al., 2008 the nose, cheek and eyelids [20], according to Al-Zou et al., 2016 the face (NOS), the eyelids and the ear [13], according
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Table 15. Correlation between different factors and DFS among NMSCHN patients.
to Marconi et al., 2016 the nose and face [26] and according to Zargaran et al., 2013 the nose, the cheek and the scalp [21] are the most common sites for occurrence of NMSCHN, noting that the nose is commonly affected in all the studies. T1 lesions represented the main T stage in this study (52%) while T2 represented 36% of lesions in the study population; this is in agreement with other studies [11] [26]. Nodular type of BCC was by far the most common in this study population (79%) similarly other studies showed nodular type predominance in BCC [9] [10] [18] [27]. Grade II for SCC and BSC was predominant in our study (61.1%) while Mahmoud et al., 2006 reported Grade I predominance (46.6%) [10]. Inspite Alternatives to the surgical management of cutaneous malignancies may be preferred under certain circumstances [11], Surgery remains the main line of treatment for NMSC [28], a recent meta-analysis comparing the different treatment modalities for NMSC demonstrated that surgical excision had superior outcomes when compared to cryotherapy, photodynamic therapy, radiotherapy, 5-flurouracil (5-FU), and imiquimod in terms of complete lesion response, clearance of NMSC, and cumulative recurrence probabilities [29]. 98.5% of our patients were operated upon as a part of the management strategy. It should be noted that head and neck skin cancers are particularly challenging to treat given the difficulty in determining the amount of tissue that should be excised to provide adequate cancer-free margins with the best functional and cosmetic outcome. In this study, we relied mainly on intra-operative frozen section analysis (IFSA) whenever available, unfortunately, it was not used in all our patients due to unavailability and sometimes due to surgeons’ reluctance leading to a high rate of positive margins (20.9%) with a significant recurrence rate (p = 0.001). Mohs Micrographic Surgery (MMS) is still not available at our institute, which was not considered a big concern by our team relying on a systemic review by Bath-Hextall et al., 2007 where surgical excision was compared to MMS and demonstrated no difference in 30-month recurrence rates in the treatment of BCC [30]. Similarly, no difference was found in the recurrence risk following treatment of recurrent BCC removed by surgical excision versus MMS [31]. A recent meta-analysis by Lansbury et al., 2013 indicated similar results for cutaneous SCC, signifying no difference between recurrence risk of surgical excision and MMS [32]. Although Bartos and Kullova 2018 stated that BCC and SCC had several clinicopathological differences and should be considered separately [33], our study didn’t show any significance regarding the distribution of both BCC and SCC in relation to different factors (Table 13).
Since NMSC only very sporadically leads to metastases, one of the most adverse clinical features of disease is local tumor recurrence. This is a relatively frequent matter in a routine dermatologic practice. According to literature data, local recurrence rates range between 2% and 4.3% [34] [35], unfortunately the recurrence rate in this study was high up to 25% due to several factors including the anatomic sites of the lesions, the size (high risk lesions), the positive margins due to unavailability of IFSA and many patients were operated upon by young surgeons and senior residents.
5. Conclusion
NMSCHN lesions should be surgically excised in specialized high volume centers with readily available peripheral margin control and should be operated by senior experienced surgeons.