Actinic Cheilitis

Background

This is a premalignant lesion seen predominantly on the vermilion of the lower lip caucasian middle-aged men with a history of sun exposure. Complete removal, usually with laser ablation, is the recommended course of treatment. If completely removed, the prognosis is excellent. If left unattended, these lesions are at increased risk to develop into squamous cell carcinoma.

OUTLINE

Epidemiology

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/
Immunohistochemistry/
Electron Microscopy

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

SYNONYMS Actinic prurigo cheilitis

EPIDEMIOLOGIC ASSOCIATIONS

Actinic prurigo cheilitis: clinicopathologic analysis and therapeutic results in 116 cases.

Vega-Memije ME, Mosqueda-Taylor A, Irigoyen-Camacho ME, Hojyo-Tomoka MT, Dominguez-Soto L.

Department of Dermatology, Dr Manuel Gea Gonzalez General Hospital, Mexico City, Mexico.

Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Jul;94(1):83-91 Abstract quote
Objective. This study describes the clinicopathologic features and therapeutic results of 116 patients with actinic prurigo cheilitis seen over an 11-year period. Study Design. A retrospective study was carried out with hospital records and a microscopic slide review from a large dermatology department in Mexico City, Mexico.

Results. The study consisted of 42 male (36.2%) and 74 female (63.8%) patients, with a male to female ratio of 1:1.7. Age ranged from 9 to 82 years (mean, 27.9 years; standard deviation, 14.2). Thirty-two cases (27.6%) were found in which cheilitis was the only manifestation of this condition. Pruritus, tingling, and pain of the vermilion were recorded in 96 cases (82.7%). Typical histopathologic findings included in most cases the presence of acanthosis, spongiosis, basal cell vacuolation, ulceration with serohematic crust formation, edema of the lamina propria, lymphocytic inflammatory infiltrate with well-defined lymphoid follicles, and variable numbers of eosinophils and melanophages. Improvement of the symptoms was obtained in 112 cases (96.5%) with sun-protective measures and diverse antiinflammatory agents. However, complete resolution of the labial lesions were more frequently achieved with the combination of topical steroids, thalidomide, and sun-protective measures (42.2%) as compared with topical steroid therapy plus sun-protection measures (16.3%; P <.005).

Conclusion. Our findings confirm that lip lesions may appear as the only manifestations of this photodermatosis and that it has typical clinical and microscopic features and should therefore be considered a specific form of cheilitis.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

Actinic cheilitis: a review of the etiology, differential diagnosis, and treatment.

Picascia DD, Robinson JK.
J Am Acad Dermatol 1987 Aug;17(2 Pt 1):255-64 Abstract quote
With today's increase in sun worshippers, the number of sun-induced skin lesions is increasing. Actinic cheilitis is the counterpart of actinic keratosis of the skin and can also develop into squamous cell carcinoma.

In this article we review the etiology, clinical spectrum, histology, differential diagnosis, and treatment of actinic cheilitis. Actinic cheilitis needs to be differentiated from many other lip conditions, and the dermatologist must be attune to its possibility whenever assessing scaly lips.

Because of its potential to develop into squamous cell carcinoma, treatment should be instituted as soon as possible.

SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

IMMUNOPEROXIDASE

CYTOKERATIN

Altered cytokeratin expression in actinic cheilitis.

Dos Santos JN, De Sousa SO, Nunes FD, Sotto MN, De Araujo VC.

Federal University of Bahia, Bahia, University of Sao Paulo, Sao Paulo, Brazil.

J Cutan Pathol 2003 Apr;30(4):237-41 Abstract quote
BACKGROUND: Actinic cheilitis (AC) is a widely recognized precancerous lesion of the lip. Varying degrees of epithelial dysplasia may be present. However, no studies have correlated epithelial changes with cytokeratin expression that might reflect the disordered maturation that is probably occurring.

METHODS: Thirty-four cases diagnosed as AC were classified according to dysplasia degree, and submitted to immunohistochemical staining for the detection of cytokeratins (CKs) 7, 8, 13, 14, 16 and 19. Normal mucosa adjacent to the lesions was also evaluated.

RESULTS: The results obtained showed that CK10 immunostained only superficial keratinized epithelial layers in 11 cases, and also intermediate spinous layers in 18 cases. Cytokeratin 14 was expressed in all epithelial layers of 31 cases, in two cases its expression was in the basal and intermediate layers, and one case was negative. Cytokeratin 13 immunostained 26 cases and was negative in eight cases. In these eight cases, CK13 was apparently replaced by CK16. Cytokeratin 16, besides these eight cases, was also expressed in the spinous intermediate layers of a further eight cases. The remaining CKs tested were all negative. No relation between the degree of dysplasia and the CK expression was noted.

CONCLUSIONS: Cytokeratin expression in AC is different from that of normal oral mucosa, and is not related to the degree of dysplasia.

ELECTRON MICROSCOPY

PROGNOSIS CHARACTERIZATION

MALIGNANCY

Actinic cheilitis and carcinoma of the lip.

Main JH, Pavone M.

Dental Department, Sunnybrook Health Science Centre, Toronto, ON.
J Can Dent Assoc 1994 Feb;60(2):113-6 Abstract quote
During dental examinations, the lips are readily overlooked. Dentists should routinely examine the lips visually and by palpation.

Actinic cheilitis is a common condition caused by damage to the lips through exposure to sunlight, and is readily diagnosed clinically. Its progress can be minimized by the use of an appropriate sun screen when outdoors.

Actinic cheilitis can undergo malignant transformation into squamous cell carcinoma. The clinical features and management of these conditions are described.

TREATMENT CHARACTERIZATION

GENERAL

IMIQUIMOD

Topical 5% imiquimod for the therapy of actinic cheilitis.

Smith KJ, Germain M, Yeager J, Skelton H.

Department of Dermatology, University of Alabama at Birmingham, 35294, USA.

J Am Acad Dermatol 2002 Oct;47(4):497-501 Abstract quote
BACKGROUND: Tissue-destructive and more selective cytotoxic therapies are the main methods used to treat actinic cheilitis. A topical immune stimulant, 5% imiquimod cream, has recently been used for treatment of cutaneous epithelial malignancies including squamous cell carcinoma in situ and basal cell carcinoma.

OBJECTIVE: Our aim was to review the results in patients who had been treated for actinic cheilitis with imiquimod cream.

METHODS: A review identified 15 patients with biopsy-proven actinic cheilitis who had been treated with topical imiquimod 3 times weekly for 4 to 6 weeks. All patients with histories consistent with facial herpes simplex or documented prior facial herpes simplex eruptions were treated with oral valcyclovir, 1 g/d, during imiquimod therapy.

RESULTS: All 15 patients showed clinical clearing of their actinic cheilitis at 4 weeks after discontinuation of the topical imiquimod. Sixty percent of the patients experienced a moderate to marked increased local reaction consisting of increased erythema, induration, and erosions or ulcerations, which in some cases continued through the period of therapy.

CONCLUSION: Imiquimod appears to have a role in the treatment of actinic cheilitis. However, the dose and duration of therapy, as well as the long-term efficacy, need to be established; and local reactions are to be expected and may not improve during therapy.

LASER

Actinic cheilitis. A treatment review.

Dufresne RG Jr, Curlin MU.

Department of Dermatology, Brown University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island, USA.

Dermatol Surg 1997 Jan;23(1):15-21 Abstract quote
BACKGROUND: Actinic cheilitis is a common premalignant condition, significant for symptoms and potential development into invasive squamous cell carcinoma. Multiple methods of treatment have been reported for this entity.

OBJECTIVE: The purpose of this article is to review and compare the accepted treatment modalities reported for actinic cheilitis.

METHODS: The English language literature was reviewed for treatment options, efficacy and adverse effects.

RESULTS: Cryosurgery, electrocautery, 5-fluorouracil, carbon dioxide laser, and scalpel vermilionectomy were all clinically effective. All therapies, with the exception of chemical peeling, appear to have a low clinical failure rate. Histological clearance of disease was demonstrated in carbon dioxide laser-treated patients. 5-Fluorouracil failed to achieve complete removal of histologic dysplasia. The carbon dioxide laser may be associated with less scarring and an improved cosmetic outcome in comparison with the scalpel vermilionectomy.

CONCLUSION: Focal actinic cheilitis is easily treated with cryosurgery or electrosurgery. Extensive actinic cheilitis requires 5-fluorouracil, carbon dioxide laser, or scalpel vermilionectomy for adequate treatment. The carbon dioxide laser offers some advantages over scalpel vermilionectomy.

Carbon dioxide laser treatment of actinic cheilitis. Clinicohistopathologic correlation to determine the optimal depth of destruction.

Johnson TM, Sebastien TS, Lowe L, Nelson BR.

Department of Dermatology, University of Michigan, Ann Arbor 48109.
J Am Acad Dermatol 1992 Nov;27(5 Pt 1):737-40 Abstract quote
BACKGROUND: The carbon dioxide laser is an effective modality for the treatment of actinic cheilitis, but the number of passes required is unknown. After each pass different visual tissue qualities are observed.

OBJECTIVE: Our purpose was to identify and characterize histologically the tissue zones seen after laser impact and thereby to determine the optimal depth of destruction of diseased tissue.

METHODS: Twenty-three biopsy specimens from 14 patients were obtained from zones of different tissue qualities after one and three passes with the laser. Specimens were histologically examined for the presence or absence of diseased epithelium and degree of thermal necrosis.

RESULTS: Complete destruction of the epithelial layer was observed in all specimens irrespective of the number of laser passes. The amount of dermal homogenization increased with multiple passes.

CONCLUSION: Treatment to the first or second surgical zone is effective for actinic cheilitis.

PHOTODYNAMIC THERAPY

Photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic cheilitis.

Stender IM, Wulf HC.

Department of Dermatology, National University Hospital, Rigshospitalet, Copenhagen, Denmark.
Br J Dermatol 1996 Sep;135(3):454-6 Abstract quote
Three patients with cheilitis were successfully treated by photodynamic therapy using the topical application of 5-aminolevulinic acid (ALA), followed by irradiation with incoherent visible light. The three patients had had, for several years, disabling lesions on the lower lip, and histopathological examination showed dysplastic lesions without signs of carcinoma.

Conventional treatments were ineffective. During photodynamic therapy, all patients reported a burning sensation when irradiated at the ALA treated area, diminishing immediately after removal of the light source, and vanishing within 4 days after treatment.

Superficial peeling began 4 days after treatment, and lasted some months. Follow-up, after 6 and 12 months, did not reveal any sign of recurrence.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

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Commonly Used Terms
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TREATMENT	CHARACTERIZATION
GENERAL
IMIQUIMOD
Topical 5% imiquimod for the therapy of actinic cheilitis. Smith KJ, Germain M, Yeager J, Skelton H. Department of Dermatology, University of Alabama at Birmingham, 35294, USA.	J Am Acad Dermatol 2002 Oct;47(4):497-501 Abstract quote BACKGROUND: Tissue-destructive and more selective cytotoxic therapies are the main methods used to treat actinic cheilitis. A topical immune stimulant, 5% imiquimod cream, has recently been used for treatment of cutaneous epithelial malignancies including squamous cell carcinoma in situ and basal cell carcinoma. OBJECTIVE: Our aim was to review the results in patients who had been treated for actinic cheilitis with imiquimod cream. METHODS: A review identified 15 patients with biopsy-proven actinic cheilitis who had been treated with topical imiquimod 3 times weekly for 4 to 6 weeks. All patients with histories consistent with facial herpes simplex or documented prior facial herpes simplex eruptions were treated with oral valcyclovir, 1 g/d, during imiquimod therapy. RESULTS: All 15 patients showed clinical clearing of their actinic cheilitis at 4 weeks after discontinuation of the topical imiquimod. Sixty percent of the patients experienced a moderate to marked increased local reaction consisting of increased erythema, induration, and erosions or ulcerations, which in some cases continued through the period of therapy. CONCLUSION: Imiquimod appears to have a role in the treatment of actinic cheilitis. However, the dose and duration of therapy, as well as the long-term efficacy, need to be established; and local reactions are to be expected and may not improve during therapy.
LASER
Actinic cheilitis. A treatment review. Dufresne RG Jr, Curlin MU. Department of Dermatology, Brown University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island, USA.	Dermatol Surg 1997 Jan;23(1):15-21 Abstract quote BACKGROUND: Actinic cheilitis is a common premalignant condition, significant for symptoms and potential development into invasive squamous cell carcinoma. Multiple methods of treatment have been reported for this entity. OBJECTIVE: The purpose of this article is to review and compare the accepted treatment modalities reported for actinic cheilitis. METHODS: The English language literature was reviewed for treatment options, efficacy and adverse effects. RESULTS: Cryosurgery, electrocautery, 5-fluorouracil, carbon dioxide laser, and scalpel vermilionectomy were all clinically effective. All therapies, with the exception of chemical peeling, appear to have a low clinical failure rate. Histological clearance of disease was demonstrated in carbon dioxide laser-treated patients. 5-Fluorouracil failed to achieve complete removal of histologic dysplasia. The carbon dioxide laser may be associated with less scarring and an improved cosmetic outcome in comparison with the scalpel vermilionectomy. CONCLUSION: Focal actinic cheilitis is easily treated with cryosurgery or electrosurgery. Extensive actinic cheilitis requires 5-fluorouracil, carbon dioxide laser, or scalpel vermilionectomy for adequate treatment. The carbon dioxide laser offers some advantages over scalpel vermilionectomy.
Carbon dioxide laser treatment of actinic cheilitis. Clinicohistopathologic correlation to determine the optimal depth of destruction. Johnson TM, Sebastien TS, Lowe L, Nelson BR. Department of Dermatology, University of Michigan, Ann Arbor 48109.	J Am Acad Dermatol 1992 Nov;27(5 Pt 1):737-40 Abstract quote BACKGROUND: The carbon dioxide laser is an effective modality for the treatment of actinic cheilitis, but the number of passes required is unknown. After each pass different visual tissue qualities are observed. OBJECTIVE: Our purpose was to identify and characterize histologically the tissue zones seen after laser impact and thereby to determine the optimal depth of destruction of diseased tissue. METHODS: Twenty-three biopsy specimens from 14 patients were obtained from zones of different tissue qualities after one and three passes with the laser. Specimens were histologically examined for the presence or absence of diseased epithelium and degree of thermal necrosis. RESULTS: Complete destruction of the epithelial layer was observed in all specimens irrespective of the number of laser passes. The amount of dermal homogenization increased with multiple passes. CONCLUSION: Treatment to the first or second surgical zone is effective for actinic cheilitis.
PHOTODYNAMIC THERAPY
Photodynamic therapy with 5-aminolevulinic acid in the treatment of actinic cheilitis. Stender IM, Wulf HC. Department of Dermatology, National University Hospital, Rigshospitalet, Copenhagen, Denmark.	Br J Dermatol 1996 Sep;135(3):454-6 Abstract quote Three patients with cheilitis were successfully treated by photodynamic therapy using the topical application of 5-aminolevulinic acid (ALA), followed by irradiation with incoherent visible light. The three patients had had, for several years, disabling lesions on the lower lip, and histopathological examination showed dysplastic lesions without signs of carcinoma. Conventional treatments were ineffective. During photodynamic therapy, all patients reported a burning sensation when irradiated at the ALA treated area, diminishing immediately after removal of the light source, and vanishing within 4 days after treatment. Superficial peeling began 4 days after treatment, and lasted some months. Follow-up, after 6 and 12 months, did not reveal any sign of recurrence.

Epidemiology
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Actinic prurigo cheilitis
EPIDEMIOLOGIC ASSOCIATIONS
Actinic prurigo cheilitis: clinicopathologic analysis and therapeutic results in 116 cases. Vega-Memije ME, Mosqueda-Taylor A, Irigoyen-Camacho ME, Hojyo-Tomoka MT, Dominguez-Soto L. Department of Dermatology, Dr Manuel Gea Gonzalez General Hospital, Mexico City, Mexico.	Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002 Jul;94(1):83-91 Abstract quote Objective. This study describes the clinicopathologic features and therapeutic results of 116 patients with actinic prurigo cheilitis seen over an 11-year period. Study Design. A retrospective study was carried out with hospital records and a microscopic slide review from a large dermatology department in Mexico City, Mexico. Results. The study consisted of 42 male (36.2%) and 74 female (63.8%) patients, with a male to female ratio of 1:1.7. Age ranged from 9 to 82 years (mean, 27.9 years; standard deviation, 14.2). Thirty-two cases (27.6%) were found in which cheilitis was the only manifestation of this condition. Pruritus, tingling, and pain of the vermilion were recorded in 96 cases (82.7%). Typical histopathologic findings included in most cases the presence of acanthosis, spongiosis, basal cell vacuolation, ulceration with serohematic crust formation, edema of the lamina propria, lymphocytic inflammatory infiltrate with well-defined lymphoid follicles, and variable numbers of eosinophils and melanophages. Improvement of the symptoms was obtained in 112 cases (96.5%) with sun-protective measures and diverse antiinflammatory agents. However, complete resolution of the labial lesions were more frequently achieved with the combination of topical steroids, thalidomide, and sun-protective measures (42.2%) as compared with topical steroid therapy plus sun-protection measures (16.3%; P <.005). Conclusion. Our findings confirm that lip lesions may appear as the only manifestations of this photodermatosis and that it has typical clinical and microscopic features and should therefore be considered a specific form of cheilitis.

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
IMMUNOPEROXIDASE
CYTOKERATIN
Altered cytokeratin expression in actinic cheilitis. Dos Santos JN, De Sousa SO, Nunes FD, Sotto MN, De Araujo VC. Federal University of Bahia, Bahia, University of Sao Paulo, Sao Paulo, Brazil.	J Cutan Pathol 2003 Apr;30(4):237-41 Abstract quote BACKGROUND: Actinic cheilitis (AC) is a widely recognized precancerous lesion of the lip. Varying degrees of epithelial dysplasia may be present. However, no studies have correlated epithelial changes with cytokeratin expression that might reflect the disordered maturation that is probably occurring. METHODS: Thirty-four cases diagnosed as AC were classified according to dysplasia degree, and submitted to immunohistochemical staining for the detection of cytokeratins (CKs) 7, 8, 13, 14, 16 and 19. Normal mucosa adjacent to the lesions was also evaluated. RESULTS: The results obtained showed that CK10 immunostained only superficial keratinized epithelial layers in 11 cases, and also intermediate spinous layers in 18 cases. Cytokeratin 14 was expressed in all epithelial layers of 31 cases, in two cases its expression was in the basal and intermediate layers, and one case was negative. Cytokeratin 13 immunostained 26 cases and was negative in eight cases. In these eight cases, CK13 was apparently replaced by CK16. Cytokeratin 16, besides these eight cases, was also expressed in the spinous intermediate layers of a further eight cases. The remaining CKs tested were all negative. No relation between the degree of dysplasia and the CK expression was noted. CONCLUSIONS: Cytokeratin expression in AC is different from that of normal oral mucosa, and is not related to the degree of dysplasia.
ELECTRON MICROSCOPY