Original papers
Facial skin cancers: general information and an overview of treatment methods

Introduction

General information





In 1998-2008, the Clinic of Plastic and Reconstructive Surgery, Medical University of Lodz, treated 398 patients with cancers located on the face. They are the most common malignancy occurring in humans [1] and a third of all cancers detected. The incidence rate is difficult to determine because of the lack of precise registration. In recent years there has been a rise in incidence in the U.S. by

10-15% annually. It is more likely in males (2 : 1). Incidence rate is 1.7%/year in the world [2] and in the Asian population [3]. In studies of Andrade 52.4% of non-melanoma cancers were found in women [4]. The most common of these is the basal-cell carcinoma (BCC) [5] and it is often not included in the registers, which causes skin cancers to occupy distant positions in them. The second most common cancer is squamous cell carcinoma (BCC/SCC = 3 : 1) [6]. In Poland they cause about 1500 deaths every year [7]. The diagnosis is based on the histopathological examination.



Factors predisposing



An increased incidence of non-melanoma skin cancers is observed in males with fair skin, poor tanning ability, blond hair, blue eyes, and depends on the age and time of exposure to sunlight. he development of skin cancer predisposition:

• UV radiation – blocks of DNA repair mechanisms, mutations in the p53 gene have been shown in over 90% of SCC and more than 50% of BCC [8]; UVB rays are particularly dangerous, and the time of exposure is of crucial importance [9];

• skin phototype (I-VI) and the related amount of melanin – the more the greater the protection, these are cancers of the white race;

• ionizing radiation – showed an increase in the incidence of BCC and SCC in radiologists and in patients with actinic dermatitis [10];

• immunosuppression – both drugs, transplants or by the action of UV radiation on the immune system (reducing the number of Langerhans cells, suppression of cellular response) [11]; in conditions associated with immunosuppression such as AIDS, an increase in the incidence of skin cancers is observed [12];

• chronic wounds and scars after burn – SCC is more likely to develop in them [13];

• chemicals – creosote, formaldehyde and others – particularly predispose to SCC [14];

• precancerous lesions of the skin, which include:

– actinic keratosis – 16% pass in the SCC [15],

– pigmented skin and xeroderma pigmentosum – a genetic disorder that affects repairing DNA damage, which occurs under the influence of UV radiation; the greatest damage occurs under the influence of UVB [16],

– keratoacanthoma [17] – described in 1889, by Hutchinson's tumor arising in areas exposed to sunlight, characterized by rapid growth (4-8 weeks), may underlie malignant cases,

– seborrhoeic wart, dermatofibroma (no precancerous lesions) [18],

– Bowen’s disease – 3-11% after years become invasive SCC, the preferred treatment is 5-FU and excision [19, 20]. According to the work of Graham et al., Bowen's disease increases the incidence of cancer of internal organs [20],

– leukoplakia – if the SCC develops on leukoplakia, the risk of metastasis is greater than in the case of actinic keratosis [21],

– Marjolin’s ulcer [22],

– Bowenoid pustulosis,

– Queyrat’s disease [21];

• Jadassohn's stigma – congenital lesion of the scalp.

Predisposing syndromes:

• Gorlin syndrome (a genetic mutation in the gene locus 9q22.3 PTCH2.), it is inherited as an autosomal dominant trait, in the form of multiple signs and is often accompanied by developmental defects and cysts of the jaw, rib defects [23, 24],

• Bazex syndrome – (BCC, hypotrichosis, hypohidrosis) and its variant Rombo syndrome [25, 26].

In the WHO classification of tumors, BCC and SCC are included in a group of squamous cell tumors originating from the basal layer (BCC) or spinal (SCC) of the epidermis.



Basal cell carcinoma



Basal cell carcinoma (carcinoma basocellulare, ba­salioma, ulcus rodens, BCC) is the most common cancer characterized by a low degree of malignancy, slow growth and a very rare formation of metastases to regional lymph nodes (lymphatic route, 0.003-0.1%) by high degrees of proficiency. It comes from the basal cell layer of the epidermis. According to the Skin Cancer Foundation, in the U.S. each year about 800,000 people get the disease. The BCC develops in the skin not previously modified or from precancerous lesions. Incidence increases with age. About 85% of BCC cases are localized in the head and neck, usually in the nose (> 25%), orbit (7%) or the external ear (6%) and lips, usually above the palate line [7, 27].

Risk factors include age, male gender, type I and II of the skin, used immunosuppressive drugs, high-fat diet. BCC also fosters the development of the earlier outbreak of BCC in a different place [28].

Factors influencing the prognosis are: tumor size (the bigger the greater the chance of recurrence), location (central part of the face (around the eyes, nose, lips) and around the ears – a high-risk BCC), the borders of change (ill-defined increase of the risk of recurrence), histological type, histological type of aggression (perineural, perivascular – increase the risk of recurrence), reoperation, used immunosuppression.

Surgical excision of primary BCC gives recurrence observed in 5 years in only about 2%. For small changes

(< 20 mm), excision with a margin of 3 mm gives a cure rate of 85%, widening the margin to 4-5 mm increases the proportion of cured cases to 95%. In the case of a morpheaform cut with a margin of 3 mm gives a cure only in 66%, so in this form it is suggested to apply a wider margin. Incomplete excision is observed in approximately 4-7% (studies in the GB and Australia). Despite incomplete excision, recurrence within 2-5 years observed in an independent research is only

30-41%. Trimming of incompletely excised BCC demonstrates the presence of malignant cells in only 45-54% of specimens in two independent histopathological studies. The decisive factor seems to be a deep cut margin [28-30].

Morphological variations are defined as follows:

1. Deep

• nodular (carcinoma basocellulare nodosum) – the most common form of BCC, 21%; nodule surrounded by characteristic non-inflammatory pearly shaft. In the central part of a nodule there may be scarring, initial size of a pinhead, pink-red focus, growing quickly. Within the nodule there may be present multiple telangiectasia and scaling, bleeds easily,

• ulcerative (carcinoma basocellulare exulcerans, historical name: penetrating ulcer – ulcus rodens) – form is characterized by deep infiltration of the tu­mor base, which could lead to destruction of the muscle and bone. A characteristic clinical BCC nodule surrounding the shaft may be in the form that is barely perceptible. It arises from a nodular variety, which under the influence of perfusion abnormalities is necrotic in the middle, with a slightly infiltrated bottom and slightly haughty, hardened edges of the pearl type, bleeds easily, has the ability to infiltrate the stroma,

• pigmentosa (carcinoma basocellulare pigmentosum),

• scleroderma (carcinoma basocellulare morphei­forme) – is a porcelain colored nodule, usually not liable to decay, focus close to the limited scleroderma, whitish, with increased cohesiveness, haughty, but slightly reduced edges, the periphery can be in the form of a pearly hill,

• cystic (carcinoma basocellulare cysticum) – localized usually on the eyelids as small, translucent nodules,

• scarring (BCC planum cicatricans): scar surrounded by a pearly shaft.

2. Superficial = crawling (basocellulare superficial carcinoma) – a form of mild and chronic course, in which superficial lesions are generally numerous, well marked out, and spread very slow. Only a shaft with a single change is present. No major breakdown or appearance of scar formation; it is difficult to establish the diagnosis early. The most common location of this form of cancer is the trunk, a variation of a surface is called Arning’s tumor (carcinoma basocellulare superficial multicentricum). All varieties of BCC are characterized by a slow process and the typical location is the face, they never harm the eye and do not take up the mucous membranes, except as an ulcerative form, infiltrating stroma only slightly. Five-year survival without metastases is given in more than 90%, the local recurrence rate is close to 50% [21].

Histological types are as follows: undifferentiated carcinoma (solidum), cystic (cysticum), glandular (adenoides), keratoticum and pigmentosum.



Squamous cell carcinoma



The second most common SCC arises from the

squamous layer of the skin’s corneum and mucous

membranes. The SCC has higher virulence (grading I-IV depending on the number of differentiated cells), and morphologically no pearly shaft surrounding the change is observed.

Early squamous cell carcinoma of the skin (carcinoma in situ) is a sharply limited red erythema. Advanced lesions are nodular with hyperkeratosis (papillary) and sometimes ulcerative. Characteristic features include the infiltration base and embankment edge changes, absence of pearly, translucent aspect and much less telangiectasia.

It is usually located on the border of the mucosa and skin in the lower part of the face, below the line connecting the corner of the mouth and ear lobe.

It is characterized by a relatively rapid growth and tendency to metastasize (3-5%), rising to 30% for the location on the border of the skin and mucous membranes, or local recurrence [31]. For diagnosis histological examination is necessary. Samples are collected through excisional biopsy, shear (biopsy), fragmented biopsy, or biopsy of lymph nodes.

There are two types of SCC:

• exophytic form (type I) characterized by the occurrence of ulcers and late metastasis,

• endophytic form (type II) growing faster than ulcerative, metastasizing faster to lymph nodes (85%) or distant (15%) [21].

The SCC grade of differentiation also depends on the individual cell structures and the tendency to keratinization. To evaluate the four-grade scale of Broders is used (undifferentiated cells to evaluate the amount of the entire tumor mass) [32].

Aim

The paper presents the fundamental histopathological differences between the carcinomas of the face, the algorithm of treatment according to the primary lesion and the related therapeutic options. It also presents the possibility of reconstruction of facial defects, depending on the location of the change on the basis of selected patients treated at the Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Lodz.

Material and methods

In the Clinic of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Lodz in 1998-2008, 398 patients were treated. The method of surgical treatment depended on the type of cancer, its stage and location. For the changes located on the face, in the advancement of T1 a simple excision and repair, in other cases, flaps or skin grafts were used.



Methods of treatment



Surgical treatment: the method of choice in the treatment of skin cancer is excision with a margin of healthy tissue [34-37]. The margin for BCC is about 5-10 mm,

and for SCC – 10-15 mm. The type of the surgical procedure depends on the character, stage and location of the tumor, the general condition of the patient and the result of histopathological examination. In the case of BCC, it is sufficient to remove the primary lesion, in the case of SCC > 2 cm lymph nodes should also be removed (according to some authors, as standard, according to others, only in more advanced cases). Undoubted benefits of surgical treatment is the high curability rate reaching 98% for BCC, good cosmetic results, short duration of treatment, the possibility of performing a histo­pathological examination.

Other treatment methods include:

• curettage and electrocoagulation (C and D curettage and electrodessication) – sometimes used for small

(< 1 cm) primary changes [38];

• Mohs micrographic surgery – microscopically controlled surgery. Full histopathological control of edges of the removed changes, ensuring completeness of excision with a minimal loss of healthy tissues, used especially in areas where it is important to avoid unnecessary loss of healthy tissue: the nose, eyelids, the area of the ear, lip; lower risk of recurrence (< 5%) [39, 40];

• chemotherapy – 5% ointment of 5-fluorouracyl for superficial BCC [41], bleomycin [42], interferon  – experimentally in BCC and SCC [43];

• radiation therapy (teleradiotherapy, brachytherapy) – good cosmetic result, cancers of the central part of the face; defects – actinic dermatitis, should be avoided at the location on the eyelids, nose, ear, reserved for patients with contraindications to surgery [44, 45];

• cryosurgery – only for small, superficial BCC changes, for the other it is not recommended, freezing with liquid nitrogen or nitrous oxide [46, 47];

• photodynamic therapy – give intravenous or topical photosensitizing substance, which, after 24-48 h accumulates in tumor cells, then radiates with the wave length of 630-660 nm or a laser – by photo-oxidation chemical reaction occurs and leads to death of cancer cells. Low efficacy, relapse is characterized by higher histological malignancy [48].

Surgical treatment of non-melanoma skin facial tumors with local art, depending on the location.

1. The forehead and scalp

Forehead skin changes with age and depends on ethnic factors. The skin is usually smooth in youth, and covered with wrinkles in the elderly. Unfortunately, there is no disposal of excess skin. When planning the treatment we pay attention to the surrounding anatomic structures. Small defects are closed primarily in a transverse or sagittal direction. Large loss of tissue is covered with the pedicle flaps, often advancement or rotation flaps.

2. Cheek, upper and lower lip

Buccal cavities, if it is not possible to close primarily within aesthetic units, we close with flaps shifted from the neighborhood, before ear – or - retroauricular, naso-labial fold or glabella. It is possible to use rotation flaps from the neck, temporal or before ear area. Large defects can also be covered with full-thickness skin grafts taken from the retroauricular, supraclavicular or medial arm area.

Small defects of the lip are cut following certain principles: small cavities are cut horizontally, losses exceeding the vermilion border are cut with Z-plasty, in the case of a partial or total excision of the lip, reconstruction is performed by moving the mucous membrane of the mouth or tongue. Large defects of the upper lip can be covered using the Abbe’s flap originating from the lower lip, flap rotation (fan flap) or perialar crescentic advancement flap. Small defects of the lower lip may be closed directly or with sliding lip tissue and closed in layers or closed using the method of Karapandzic. Defects in excess of 1/3 of the lower lip require lip switching procedures (Gilles flap, McGregor flap, Estlander flap) or tubular flap (Figures 1-8).

3. Upper and lower eyelid

Small defects are cut and supplied with local tissue advancement. For the larger defects we can use free skin grafts (FTSG- full-thickness skin graft) taken from behind the ear or the opposing side of the eyelids. Extensive loss of the upper eyelid can be covered with flaps (Mustarde’s flap, moved from the cheek, or Abbe’s flap taken from the opposite lid). Sometimes there is a need to cover the defect with muco-cartilage graft from the nasal septum or cartilage of the auricle. Large defects of the

lower lid are supplied using local flaps (Mustarde’s flap, Frickie’s flap or advancement flap from cheek). For the reconstruction of the upper and lower lid, flaps from the forehead can be used (Figures 9-16).

4. Nose

For the closure of defects after removal of nasal tumors various techniques of flaps can be used. In the case of location on the dorsum of the nose, flaps from glabella or forehead are preferred: advancement (Rintal, Schmidt), bilobed flaps, rotation-advancement flaps of residual dorsal skin. In the case of the lateral part of the nose, the preferred options are bilobed flaps, rotation or advancement moved from the neighborhood (Reinwald, McGregor) or from the nasolabial fold. For reconstruction of nostrils, a composed graft from auricle can be used. If more complex reconstruction is necessary (wings) we can use the whole middle part of the forehead, sometimes prepared before by the expander. In the case of total reconstruction of the nose, a flap from the forehead can be used or the nose can be prefabricated (on the forearm) and transposed by microvascular techniques (Figures

17-22).

5. Earlobe

Small defects of the auricle are supplied with wedge excision and primary closure. Local flaps from the neighborhood or retroauricular flap can be used (Figures 23-24).

Conclusions

Despite enormous progress in medical science, surgery remains the method of choice in treating facial cancers. Only the primary cut and the suitable technique of plastic surgery, selected individually for each patient provide satisfactory results.

References

 1. Miller S. Etiology and pathogenesis of basal cell carcinoma. Clinics in Dermatology 1995; 13: 527-36.

 2. Parkin DM, Pisani P, Ferley J. Global cancer statistics CA cancer J Clin 1999; 49: 33-64.

 3. Adinarayan M, Krishnamurthy S. Clinicopathological evaluation of nonmelanoma skin cancer. Indian J Dermatol 2011; 56: 670-2.

 4. Andrade P, Brites M, Vieira R, et al. Epidemiology of basal cell carcinomas and squamous cell carcinoma in Department of Dermatology – a 5 year reviev. An Bras Dermatol 2012; 87: 212-9.

 5. Vitaliano PP, Urbach F. The relative importance of risk factors in nonmelanoma carcinoma. Arch Dermatol 1980; 116: 454-6.

 6. Kordek, et al. Onkologia Podręcznik dla studentów i lekarzy. Via Medica, Gdańsk 2007; 41: 271-9.

 7. Pearl DK, Scott EL. The anatomical distribution of skin cancers. Int J Epidemiol 1986; 15: 502-6.

 8. Brash DE, Ziegler A, Jonason AS, et al. Sunlight and sunburn in human skin cancer: p53, apoptosis and tumor promotion. Invest Dermatol Symp Proc 1996; 1: 136-42.

 9. Stern RS, Lange R. Non-melanoma skin cancer occurring in patients treated with PUVA five to ten years after first treatment. J Invest Dermatol 1988; 91: 120-4.

10. Ron E, Modan B, Preston D. Radiation-induced skin carcinomatosis of the head and neck. Radiation Res 1991; 125: 318.

11. Birkeland SA, Storm HH, Lamm LU, et al. Cancer risk after renal transplantation in the Nordic countries, 1964-1986. Int J Cancer 1995; 60: 183-9.

12. Franceschi S, Dal Maso L, Arniani S, et al. Risk of cancer other than Kaposi’s sarcoma and non- Hodgkin’s lymphoma in persons with AIDS registry linkage study. Br J Cancer 1998; 78: 966-70.

13. Hahn SB, Kim DJ, Jeon CH. Clinical study of Marjolin’s ulcer. Yonsei Med J 1990; 31: 234.

14. Yuspa SH. Cutaneous chemical carcinogenesis. J Am Acad Dermatol 1986; 15: 1031-44.

15. Glogau RG. Actinic keratoses – scientific evaluation and public health implications: the risk of progression to invasive disease. J Am Acad Dermatol 2000; 42: 23-4.

16. Stone N, Reed J, Mahood J, et al. Xeroderma pigmentosum, the role of photo testing. Br J Dermatol 2000; 143: 595-7.

17. Mc Kenna KE, Somerville JE, Walsh MY, et al. Basal cell carcinoma occurring in association with dermatofibroma. Dermatology 1993; 187: 54-7.

18. Jones EW, Heyl T. Naevus sebaceous: a report of 140 cases with special regard to the development secondary malignant tumors. Br J Dermatol 1970; 82: 99-117.

19. Wyrzykowska N, Więckowicz-Rosińska A, Bartoszak L, et al. Bowen‘s disease and basal cell carcinoma in a renal transplant recipient – case report. Postep Derm Alergol 2011; 28: 138-41.

20. Graham JH, Helwig EB. Bowen’s disease and its relationship to systemic cancer. Arch Dermatol 1959; 80: 133-59.

21. Lever WF. Tumors and cysts of the epidermis. In: Histopathology of the skin. Lever WF, Schaumberg-Lever S (eds). 7th ed. JB Lippincott, Philadelphia 1990; 546.

22. Konigova R, Rychterova V. Majrolin’s ulcer. Acta Chir Plast 2000; 42: 91.

23. Takata M. Nevoid basal cell carcinoma syndrome. Nippon Rinsho 2000; 58: 1376-80.

24. Lacour JP. Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms. Br J Dermatol 2002; 146 (Suppl 61): 17-9.

25. Gherardini G, Bhatia N, Stal S. Congenital syndromes associated with nonmelanoma skin cancers. Clin Plast Surg 1997; 24: 655.

26. Wong CMS, Strange RC, Lear JT. Clinical review. Basal cell carcinoma. BMJ 2003; 327: 794-8.

27. Scrivener Y, Grosshans E, Cribier B. Variations of basal cell carcinomas according to gender, age, location, and histopathological subtype. Br J Dermatol 2002; 147: 41-7.

28. Telfer N, Colver G, Morton C. Guidelines fort he menagement of basal cell carcinoma. Br J Dermatology 2008; 159: 35-48.

29. Sartore L, Lancerotto L, Salmaso M, et al. Facial basal cell carcinoma: analysis of recurrence and follow up strategies. Oncol Rep 2011; 26: 1423-9.

30. Silverman MK, Kopf AW, Bart RS. Recurrence rates of treated basal cell carcinomas: surgical excision. J Dermatol Surg Oncol 1992; 18: 471.

31. Rove DE, Carrol RJ, Day CL Jr. Prognostic factors for local recurrence metastasis and survival rates in squamous cell carcinoma of the skin, ear and lip. Implications for treatment modality selection. J Am Acad Dermatol 1992; 266: 976-90.

32. Broders AC. Squamous-cell epithelioma oft he skin. Ann Surg 1921; 73: 141.

33. Mathes SJ. Plastic surgery. Vol. 5. Saunders Elsevier, Phi­la­delphia 2006.

34. Rank BK, Wakefield AR. Surgery of basal cell carcinoma. Br

J Surg 1958; 45: 531-47.

35. Lukic D, Karabeg R, Jeremic P, et al. The results of treatment of basocdellular carcinomas of the head skin. Med Arh 2012; 66: 169-72.

36. Anthony ML. Surgical treatment of nonmelanoma skin cancers. AORN J 2000; 71: 552-4.

37. Geisse JK. Comparison of treatment modalities for squamous cell carcinoma. Clin Dermatol 1995; 13: 621-6.

38. Salasche SJ. Status of curettage ad desiccation in the treatment of rimary basal cell carcinoma. J Am Acad Dermatol 1984; 10: 285-7.

39. Lowrence CM. Moh’s micrographic surgery for basal cell carcinoma. Clin Exp Dermatol 1999; 24: 130-3.

40. Veronese F, Farinelli P, Zavatarro E, et al. Basal cell carcinoma oft he head region: therapeutic results of 350 lesions treated with Mohs micrographic surgery. J Eur Dermatol Venerol 2012; 26: 838-43.

41. Goette DK. Topical chemotherapy with 5-fluorouracil. J Am Acad Dermatol 1981; 6: 633-49.

42. Gargiulo M, Papa A, Capasso P, et al. Electrochemotherapy for non-melanoma head and neck cancers: clinical outcomes in 25 patients. Ann Surg 2012; 255: 1158-64.

43. Chimenti S, Peris K, Di Cristofaro S, et al. Use of recombinant interferon alfa-2b in the treatment of basal cell carcinoma. Dermatology 1995; 190: 214-7.

44. Nag S, Caro ER, Demanes JD, et al. The American Brachytherapy Society recommendations for high dose rate brachytherapy for head and neck carcinoma. Int J Oncol Biol Phys 2001; 50: 1190-8.

45. Locke J, Karimpour S, Young G, et al. Radiotherapy for

epithelial skin cancer. Int J Radiat Oncol Bio Phys 1990; 19: 235-42.

46. Kuflik EG, Gage A. The five-year cure rate achieved by

cryosurgery for skin cancer. J Am Acad Dermatol 1991; 24: 1002-4.

47. Gaitanis G, Alexopoulos EC, Bassukas ID. Cryosurgery is more effective in the treatment of primary, non superficial basal cell carcinomas when applied during and not prior to five week imiquimod course: a randomized, prospective, open-label study. Eur J Dermatol 2012; 21: 952-8.

48. Flechter S, Skaria A, Nievergelt H, et al. Facial basal cell carcinomas recurring after photodynamic therapy: a retrospective analysis of histological subtypes. Dermatology 2012; 224: 346-51.