Non-Melanoma Skin Cancer Tumor's Characteristics and Histologic Subtype as a Predictor for Subclinical Spread and Number of Mohs Stages required to Achieve Tumor-Free Margins.
It minimizes any additional morbidity associated to lesion excision without margin control, as well as improves functionality and cosmetic outcomes by sparing uninvolved skin (4). Although highly effective, MMS can be time consuming and costly. Therefore, identifying skin cancer features that can help predict their behavior may help guide the surgeon, as well as the patient's expectations, prior to MMS.
Basal cell carcinomas (BCCs) tend to grow slowly and are associated with less risk of metastasis (0.1%) when compared to squamous cell carcinomas (SCCs) (2-10%), but can be locally aggressive if left untreated (5). Nodular and superficial BCC (sBCC), as well as BCCs with lack of perineural invasion are considered to be low-risk due to their low recurrence rate (6). On the other hand, micronodular, morpheaphorm, sclerosing, infiltrative, and basosquamous subtypes are considered to be high-risk due to their tendency for recurrence (6, 7, 8). These high recurrence rates are associated to the tumor's diffuse growth pattern and subclinical extension (9). BCCs of non-aggressive histologic subtypes are associated with less MMS stages when compared to their aggressive counterpart (10).
In the US, the 5-year recurrence rate for primary BCCs after MMS is as low as 1.0% (4). When compared with recurrence rates after surgical excision (3.2-10% in primary BCCs and >17% in recurrent BCCs), and taking into consideration the additional treatments these patients will require, MMS seems to be a superior and more cost-effective treatment modality (1, 2).
The histologic grade of (SCCs) and their recurrence rate correlate; moderately and poorly differentiated SCCs are considered high-risk due to their tendency to recur after treatment (6). Perineural and single cell SCCs are also classified under high-risk, whereas the well-differentiated SCCs are considered low-risk tumors (6). High-risk SCCs have also been shown to require more MMS stages for clearance when compared to low-risk SCC subtypes (11).
Tumor characteristics such as location, prior management, and pre-operative size, are also essential in predicting tumor behavior. The nose, ears, eyelids and temples have been identified as high-risk anatomic sites for non-melanoma skin cancer (NMSC) (12, 13) most likely associated to the presence of embryonic fusion planes (12, 14), extensive nerve populations, the perichondrium and periosteum closely associated to the dermis (15), or sebaceous glands that can store isolated groups of malignant cells (16). Tumor location can also serve as a predictor for metastasis, such as the case for SCCs located on the ear or lip (17, 18). Other tumor characteristics attributed to high-risk lesions are location on acral extremities or genitalia as well as tumor size larger than 2 cm (19). In addition, invasive behavior has been linked to recurrent tumors (20). The pathophysiology is most likely explained by a disturbance of a cell's immune function secondary to initial treatment and subsequent scar tissue formation, which locks in tumor cells that can eventually leak causing recurrence (21, 22).
The purpose of this study is to determine risk factors that could identify lesions with increased likelihood of requiring more extensive surgery. It is a retrospective medical chart review comparing tumor characteristics and NMSC histologic subtypes with the extent and complexity of the associated MMS.
Patients and Methods
This study was conducted at the Department of Dermatology of the University of Puerto Rico and the Institutional Review Board granted approval for the study. A retrospective review of medical charts dating from August 2013 to April 2015 was conducted of 312 patients scheduled for surgery with the same Mohs surgeon (S.V.N.). Exclusion criteria are depicted in Figure 1. In patients with multiple and clinically distinct tumors, each lesion was considered a separate tumor.
A total of 219 cases were analyzed. BCCs were subclassified as nodular, micronodular, morpheaphorm, superficial, basosquamous and infundibulocystic. Although there are several types of SCCs (e.g. pseudovascular, spindle cell, adenoid, etc.), there are rare and were not present in our cohort. Therefore, SCCs were classified as in situ or invasive. Variables examined included: patients' age and gender, tumor histologic subtype, lesion anatomic location, recurrence status, initial lesion size, number of MMS stages, defect size after MMS, reconstructive technique used, and final closure size. Two or more MMS stages were considered a criterion for extensive subclinical spread.
Previously untreated or incompletely excised neoplasms were classified as primary and those previously treated with apparent clinical or histopathologic success were considered recurrent. Tumors were also classified according to their location. The ear, eyelid, nose, and lip were classified as high-risk anatomic zones while all other locations were considered low-risk. Neoplasms of the ear, nose, and eyelid were subclassified based on specific subunits.
Clinical visible margins of the lesions were determined prior to MMS and, in most cases; neoplasms were excised with a 2-mm margin per stage. In cases of clinically aggressive SCCs (> 4cm), 4 mm margins were used per stage until a tumor-free plane was reached. The initial biopsy histopathologic slides were collected and reviewed by two dermatopathologists (J.L.S. and J.E.S.) to determine the tumor's histologic subtype. In some cases, a mixed histologic pattern was observed. In this scenario, neoplasms were classified according to the dominant pattern.
Data entry and statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) version 20. Descriptive statistics, one-way ANOVA, Chi-square test and independent T-test were used in data analysis.
The mean patient age was 65.89 years old; 103 (47%) were males and 116 (53%) were females. Most tumors were primary (91.8%), while 18 (8.2%) had been previously treated. Tumor characteristics are described in Table 1. Regarding tumor laterality, 97 (44.3%) were located on the left side and 97 (44.3%) on the right side, whereas midline lesions comprised 11.4% (n=25) of the tumors. Furthermore, 109 (49.8%) were located in a high-risk zone.
Average initial tumor size, final defect size, as well as number of MMS stages needed for tumor removal per histological subtype is illustrated in Table 2. An initial lesion size between 0.50-1.50 cm characterized 62% of the neoplasms. A total of 113 (51.6%) tumors were cleared after one stage of MMS and 106 (48.4%) tumors required two or more stages. Tumors with an average initial size of 1.32 cm required one stage, whereas tumors with an average initial size of 1.67 cm required two or more MMS stages for clearance (p value= .011).
The mean number of stages required to clear micronodular and morpheaform/infiltrative BCCs (n= 34) was 2.03, while nodular and superficial BCCs (n= 125) needed a mean of 1.57 stages (p value= .011). In situ SCCs and invasive SCCs cleared with a mean of 1.56 and 1.67 stages, respectively (p value= .701).
Eighteen tumors (8%) were considered recurrent at initial treatment with MMS. The average initial size of these tumors was 2.35 cm whereas primary tumors had a mean initial size of 1.41 cm (p value < .001). Recurrent and primary tumors had a mean final defect size of 3.42 cm and 2.01 cm, respectively (p value < .001). Among the eighteen recurrent cases, fourteen (77.8%) required two or more stages to be cleared. Furthermore, the mean number of stages required for complete tumor removal was 2.22 for recurrent tumors and 1.61 for primary tumors (p value = .006).
A total of 167 defects (76.3%) were repaired using the following techniques: linear (50.3%), skin graft (23.9%), flap (23.4%), or a combination of these (2.4%). Defects allowed to heal by secondary intention (n= 45) were mostly located on the ear (n=10; 22.2%) and scalp (n=5; 11.1%) A significant association between tumor location and repair type was found (p value < .001). The major contributors to this association were cheek and forehead with linear repair; ear and scalp with secondary intention healing; nose with skin graft; and eyelid with referrals. A total of 7 cases were referred to another service for reconstruction; of these, 4 (57.1%) were eyelid repairs.
An increase in the worldwide incidence of NMSCs has resulted in many studies evaluating different surgical and nonsurgical treatment modalities (23-25). Management considerations are based on both patient and tumor characteristics (6). A malignancy's inconspicuous subclinical extension into surrounding tissue suggests that visual estimates of tumor perimeters may be insufficient, resulting in some cases in inadequate removal and increased likelihood of recurrence (18, 26, 27). MMS provides high cure rates as it allows examination of 100% of the peripheral and deep margins of the tumor, whereas, histologic assessment of standard excisions examines only 0.2% of the surgical margins (23, 25, 28, 29). The analysis of tumor characteristics conducted in our study can help identify risk factors associated to NMSC that could help predict their behavior, guide the clinicians management approach, as well as patient's anticipations.
In our data, 85.8% of tumors were located in the head. This predilection may be explained by increased sun exposure of the region (23). Various studies have described how 70-98% of skin cancers occur in the head and neck (6, 23, 30-32). Moreover, in accordance with the findings of Paoli et al. (4), the most frequent location for BCCs in our study was the nose (28.8%). Previously published studies have identified the nose, eyelids, lips and peri-auricular regions as high-risk locations showing deep invasion and higher recurrence rates (4, 12, 23, 33). These locations have a high density of hair follicles and sebaceous glands that may create nests for tumor cells (16). In addition, these locations are embryologic cleavage planes that provide relatively little resistance to tumor invasion (1, 6, 14, 23). As described by Leibovitch et al. (23) and Salasche et al. (16), our data demonstrates how lesions on high-risk zones required more than one MMS stage for tumor clearance. In a study by Batra et al. (26), the highest odds ratio (OR) for predictive risk factors of NMSC with aggressive subclinical extension were location of the lesion (i.e., eyelid, temple, and ear helix), and tumor size (34). Similarly, our study showed a higher prevalence of invasive SCCs on the nose (15.6%) and eyelids (13.3%), which are considered high-risk anatomic zones, while the most common location for in situ SCCs was the extremities.
Tumor size may also be an indicator of subclinical spread. Large BCC tumors may show extensive subclinical growth known as the "iceberg phenomenon", wherein part of the tumor is not visible to the surgeon (1, 6). Mohs identified a tumor size greater than 2 cm as an indication for MMS based on a higher likelihood of recurrence (35). In this study, a perioperative size [greater than or equal to] 1.67 cm proved to be a significant predictor of microscopic spread, consistent with other studies that depict gradation of risk with increasing tumor size (1, 6, 13, 26).
Using the number of MMS stages as an indicator of extensive subclinical spread, our study showed that infiltrating/morpheaform/micronodular histologic BCCs subtypes, in comparison with nodular and superficial histologic subtypes, were associated with a significantly higher number of MMS stages. Therefore, these BCC subtypes are more difficult to eradicate and tend to have inconspicuous extension when compared with nodular/superficial BCCs. Aggressive histologic subtypes accounted for 20.6% of the BCC tumors in this study in accordance to previous studies which often cite a 15% frequency of aggressive subtypes (36). Evidence suggests that histologic subtype of BCCs influences tumor behavior (37-41). Sexton et al. (42) and Johnson et al. (43) showed that certain BCC histologic subtypes (morpheaform, infiltrative, micronodular, and mixed patterns) of primary BCCs are more likely to have positive margins after excision. A previous study found that morpheaform tumors were 2.3 times as likely to demonstrate extensive subclinical extension when compared to primary nodular BCC (26, 44). Published data on the incidence and clinical characteristics of SCCs with aggressive subclinical extension are limited. In this study, in situ and invasive SCCs required similar stages for clearance. The degree of SCC differentiation and perineural invasion were not assessed. However, conclusions regarding the behavior of in situ SCCs compared to invasive SCCs are difficult to determine because the low number of SCC cases included in this study (n = 54) hinders the breadth of statistical analysis.
In our study, the initial size for recurrent and primary tumors was 2.35 and 1.41, respectively. Recurrent tumors in our sample required an average 2.22 stages for complete clearance when compared to primary tumors, which required a mean of 1.61 stages to be cleared. The final defect size was also larger for recurrent tumors when compared to primary tumors. Studies have found that recurrent tumors tend to be larger than primary tumors, require more MMS stages, result in larger post-excision defect size and are associated to aggressive histologies (23). Increased risk of recurrence is seen in SCCs that are large, located in high-risk locations, moderately differentiated, poorly differentiated, perineural, and single cell SCC (6, 45). A possible explanation lies in how previous treatments may decrease local host defenses, causing multiple foci of unconnected tumor, or cause entrapment of tumor cells in scar tissue that are subsequently released causing recurrence (21, 22, 26).
The retrospective nature of this study limits its analytic scope. The fact that all cases were obtained from the medical chart of a single, government health facility where patients tend to arrive with more advanced disease is another limitation to consider. Furthermore, MMS frozen sections were not reviewed and most of the initial biopsy specimens were partial tumor shave biopsies therefore preventing complete histologic examination for tumor subtype determination. The histologic subtype declared for an initial biopsy does not always correlate with the subtype of the final Mohs stage. This may be due to the presence of a more aggressive subtype in the depth or periphery of the tumor (46), which is difficult to appreciate in a shave biopsy specimen. Furthermore, SCC histologic subtypes and their correlation with MMS were not assessed.
Our study was characterized by a high percentage of head and neck cases. The distribution of anatomic locations and histologic subtypes described was comparable to other previously mentioned studies. In our study, primary BCCs of the nodular subtype usually required one MMS stage to clear. Furthermore, the most important predictors of extensive subclinical spread for BCC subtypes are morpheaform/infiltrative, micronodular and lesion recurrence as described in our series. Therefore, wider margins should be obtained when excising micronodular, infiltrative, and morpheaform BCCs, as previously reported by other investigators (39, 40, 47). In our data, recurrent tumors were larger than primary tumors, had a larger post-excision defect, a more extensive subclinical extension, and required more stages of excision. High-risk locations and perioperative size could help predict the occurrence of aggressive neoplasms.
By providing a risk scale for subclinical spread and aggressive behavior influenced by histologic subtype, the surgeon can be particularly vigilant when examining frozen sections of high-risk tumors. Furthermore, surgeons can anticipate final defect size, plan for appropriate reconstruction, accommodate their operative schedules depending on the repair's complexity and the surgical time, as well as guide their patients in terms of pre- and post-operative expectations.
We thank Julio E. Sanchez, MD for his contribution reviewing the histopathologic slides.
(1.) Rowe DE, Carroll RJ, Day CL Jr. Mohs surgery is the treatment of choice for recurrent (previously treated) basal cell carcinoma. J Dermatol Surg Oncol 1989;15:424-431.
(2.) Rowe DE, Carroll RJ, Day CL Jr. Long term recurrence rates in previously untreated (primary) basal cell carcinoma: Implications for patient follow-up. J Dermatol Surg Oncol 1989;15:315-328.
(3.) Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs micrographic surgery for primary and recur- rent basal cell carcinoma of the face: a prospective, randomized controlled trial with 5 years follow-up. Lancet Oncol 2008;9:1149-1156.
(4.) Paoli J, Daryoini S, Wennber AM, et al. 5-year recurrence rated of Mohs Micrographic Surgery for Aggressive and Recurrent Facial Basal Cell Carcioma. Acta Derm Venereol 2011;91:689-693.
(5.) Domarus H, Stevens PJ. Metastatic basal cell carcinoma. Report of five cases and review of 170 cases in the literature. J Am Acad Dermatol 1984;10:1043-1060.
(6.) Lazareth V. Management of non-melanoma skin cancer. Semin Oncol Nurs 2013;29:182-194.
(7.) Drake LA, Dinehart SM, Goltz RW, et al. Guidelines of care for Mohs micrographic surgery. American Academy of Dermatology. J Am Acad Dermatol 1995;33:271-278.
(8.) Telfer NR, Colver GB, Morton CA. Guidelines for the management of basal cell carcinoma. Br J Dermatol 2008;159:35-48.
(9.) Spencer JM. Basal cell carcinoma. In: Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I, eds. Treatment of skin disease: Comprehensive therapeutic strategies, expert consult. Ed 3. China: Elsevier Saunders; 2010. 616:75-79.
(10.) Ro KW, Seo SH, Son SW, Kim IH. Subclinical Infiltration of Basal Cell Carcinoma in Asian Patients: Assessment after Mohs Micrographic Surgery. Ann Dermatol 2011;23:276-281.
(11.) Goldenberg A, Ortiz A, Kim SS, Jiang SB. Squamous cell carcinoma with aggressive subclinical extension: 5-year retrospective review of diagnostic predictors. J Am Acad Dermatol 2015;73:120-126.
(12.) Mora RG, Robins P. Basal-cell carcinomas in the center of the face: special diagnostic, prognostic and therapeutic considerations. Dermatol Surg Oncol 1978;4:315-21.
(13.) Silverman MK, Kopf AW, Bart RS, Grin CM, Levenstein MJ. Recurrence rates of treated basal cell carcinomas, Part 3: Surgical excision. J Dermatol Surg Oncol 1992;18:471-476.
(14.) Panje WR, Ceilley RI. The influence of embryology of the mid-face on the spread of epithelial malignancies. Laryngoscope 1979; 89:1914-1920.
(15.) Wentzell JM, Robinson JK. Embryonic fusion planes and the spread of cutaneous carcinoma: a review and reassessment. J Dermatol Surg Oncol 1990;16:1000-1006.
(16.) Salasche SJ. Curettage and electrodesiccation in the treatment of mifacial basal cell epithelioma. J Am Acad Dermatol 1983; 8:496-503.
(17.) Kossard S, Epstein EH Jr, Cerio R, et al. Basal cell carcinoma. In: LeBoit PE, Burg G, Weedon D, Sarasin A, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Skin Tumours. Lyon: IARC Press, 2006:10, 13-19.
(18.) Miller DL, Weinstock MA. Non-melanoma skin cancer in the United States: incidence. J Am Acad Dermatol 1994;30:774-778.
(19.) Wolf DJ, Zitelli JA. Surgical margins for basal cell carcinoma. Arch Dermatol 1987;123:340-344.
(20.) Betti R, Menni S, Radaelli G, Bombonato C, Crosti C. Micronodular basal cell carcinoma a distinct subtype? Relationship with nodular and infiltrative basal cell carcinomas. J Dermatol 2010;37:611-616.
(21.) Smith SP, Grande DJ. Basal cell carcinoma recurring after radiotherapy: a unique, difficult treatment subclass of recurrent basal cell carcinoma. J Dermatol Surg Oncol 1991;17:26-30.
(22.) Wagner RF Jr, Cottel WI. Multifocal recurrent basal cell carcinoma following primary tumor treatment by electrodesiccation and curettage. J Am Acad Dermatol 1987;17:1047-1049.
(23.) Leibovitch I, Huilgol SC, Selva D, Richards S, Paver R. Basal Cell Carcinoma treated with Mohs surgery in Australia I, Experience over 10 years. J Am Acad Dermatol 2005:53:445-451.
(24.) Thissen MR, Neumann MH, Schouten LJ. A systematic review of treatment modalities for primary basal cell carcinomas. Arch Dermatol 1999;135:1177-1183.
(25.) Kuijpers DI, Thissen MR, Neumann MH. Basal cell carcinoma: treatment options and prognosis, a scientific approach to a common malignancy. Am J Clin Dermatol 2002;3:247-259.
(26.) Batra RS, Kelley LC. Predictors of extensive subclinical spread in nonmelanoma skin cancer treated with Mohs micrographic surgery. Arch Dermatol 2002;138:1043-1051.
(27.) Bieley HC, Kirsner RS, Reyes BA, Garland LD. The use of Mohs micrographic surgery for determination of residual tumor in incompletely excised basal cell carcinoma. J Am Acad Dermatol 1992; 26:754-756.
(28.) Abide JM, Nahai F, Bennet RG. The meaning of surgical margins. Plast Reconstr Surg 1984;73:492-496.
(29.) Rapini RP. Comparison of methods for checking surgical margins. J Am Acad Dermatol 1990; 23: 288-294.
(30.) Scrivener Y, Grosshans E, Cribier B. Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. Br J Dermatol 2002;147:41-47.
(31.) Bastiaens MT, Hoefnagel JJ, Bruijn JA, Westendorp RG, Vermeer BJ, Bouwes Bavinck JN. Differences in age, site distribution and sex between nodular and superficial basal cell carcinomas indicate different type of tumors. J Invest Dermatol 1998;110:880-884.
(32.) Gordon R. Skin cancer: an overview of epidemiology and risk ractors. Semin Oncol Nurs 2013;29:160-169.
(33.) Farasat S, Yu SS, Nell VA, et al. A new American Joint Committee on Cancer staging system for cutaneous squamous cell carcinoma: creation and rationale for inclusion of tumor (T) characteristics. J Am Acad Dermatol 2011;64:1051-1059.
(34.) Allen KJ, Cappel MA, Killian JM, Brewer JD. Basosquamous carcinoma and metatypical basal cell carcinoma: a review of treatment with Mohs micrographic surgery. Int J Dermatol 2014;53:1395-1403.
(35.) Mohs, FE. Chemosurgery: Microscopically Controlled Surgery for Skin Cancer. Springfield, 1ll Charles C Thomas Publisher. 1978; 1-29: 153-164.
(36.) Weedon D. Tumors of the epidermis. In: Skin pathology. London: Churchill-Livingstone; 1997. pp. 648-651.
(37.) Jacobs GH, Rippey JJ, Altini M. Prediction of aggressive behavior in basal cell carcinoma. Cancer 1982;49:533-537.
(38.) Lang PG Jr, Maize JC. Histologic evolution of recurrent basal cell carcinoma and treatment implications. J Am Acad Dermatol 1986; 14: 186-196.
(39.) Leffell DJ, Headington JT, Wong DS, Swanson NA. Aggressive-growth basal cell carcinoma in young adults. Arch Dermatol 1991;127: 1663-1667.
(40.) Siegle RJ, MacMillan J, Pollack SV. Infiltrative basal cell carcinoma, a nonsclerosing subtype. J Dermatol Surg Oncol 1986;12:830-836.
(41.) Salasche SJ, Amonette RA. Morpheaform basal cell epitheliomas, a study of subclinical extensions in a series of 51 cases. J Dermatol Surg Oncol 1981;7:387-394.
(42.) Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of basal cell carcinoma. Study of a series of 1039 consecutive neoplasms. J Am Acad Dermatol 1990;23:1118-1126.
(43.) Johnson TM, Tromovitch TA, Swanson NA. Combined curettage and excision: a treatment method for primary basal cell carcinoma. J Am Acad Dermatol 1991;24:613-617.
(44.) American Cancer Society (online 20 November 2006). What is nonmelanoma skin cancer? Available at: Url: http://www.cancer.org/docroot/ CRI/content/CRI_2_2_1X_How_many_people_get_nonmelanoma_ skin_cancer_51.asp?sitearea= (accessed December 1, 2016).
(45.) Bhambri S, Dinehart S, Bhambri A. Squamous cell carcinoma. In: Rigel DS, Robinson JK, Ross M, Friedman RJ, Cockerell CJ, Lim HW, et al., eds. Cancer of the skin. Ed 2. Philadelphia: Elsevier Saunders; 2011: pp. 124-139.
(46.) Orengo I, Salasche S, Fewkes J, Khan J, Thornby J, Rubin F. Correlation of histologic subtypes of primary basal cell carcinoma and number of Mohs stages required to achieve a tumor-free plane. J Am Acad Dermatol 1997;37:395-397.
(47.) Hendrix JD, Parlette HJ. Micronodular basal cell carcinoma: a deceptive histologic subtype with frequent clinically undetected tumor extension. Arch Dermatol 1996;132:295-298.
Aileen Santos-Arroyo, MD; Osward Y. Carrasquillo, MD, MPH; Rocio Cardona, MD; Jorge L. Sanchez, MD; Sheila Valentin-Nogueras, MD
Department of Dermatology, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
The author/s has/have no conflict/s of interest to disclose.
Address correspondence to: Osward Y. Carrasquillo, MD, MPH, Department of Dermatology, University of Puerto Rico Medical Sciences Campus, PO Box 365067 San Juan, PR 00936-5067. Email: firstname.lastname@example.org
Caption: Figure 1. Exclusion criteria
Table 1. Tumor characteristics n=219 % Histopathology Nodular BCC 121 55.3 SCC invasive 45 20.5 Micronodular BCC 21 9.6 Morpheaphorm BCC 13 5.9 SCC in situ 9 4.1 Superficial BCC 4 1.8 Basosquamous BCC 3 1.4 Infundibulocystic BCC 3 1.4 Location Nose 63 28.8 Cheek 37 16.9 Forehead 22 10.0 Eyelid 20 9.1 Ear 15 6.8 Extremities 14 6.4 Temple 12 5.5 Lip 11 5.0 Trunk 10 4.6 Neck 8 3.7 Scalp 6 2.7 Chin 1 0.5 Stages 1 stage 113 51.6 [greater than or equal to] 2 stages 106 48.4 BCC, Basal Cell Carcinoma; SCC, Squamous Cell Carcinoma Table 2. Average initial tumor and final defect size, and number of MMS stages needed for tumor-free margins per histological subtype Mean initial Mean Final Mean number size (cm) defect of stages size (cm) Histopathology All (n=219) 1.49 2.12 1.66 Nodular BCC 1.32 1.90 1.57 Micronodular BCC 1.05 1.60 1.95 Infundibulocystic BCC 1.10 1.67 2.33 Morpheaphorm BCC 2.12 3.18 2.15 Basosquamous BCC .83 1.30 1.00 Superficial BCC 2.18 2.65 1.25 SCC in situ 1.67 2.42 1.56 SCC invasive 1.93 2.64 1.67 BCC, Basal Cell Carcinoma; SCC, Squamous Cell Carcinoma