Bowen's disease

Bowen's disease (squamous cell carcinoma in situ) is a premalignant dermatosis characterized clinically by an asymptomatic, scaly or crusted, erythematous plaque. Histologic findings include atypical keratinocytes, multinucleated and dyskeratotic cells, and abnormal mitotic figures throughout the epidermis. [1-5] Since this condition can masquerade as a benign dermatosis, the lesions are often present for several years before the correct diagnosis is established. This article describes a case of Bowen's disease, in which the lesion appeared as a dermatitis, and reviews the salient features of this condition.

Illustrative Case

A 47-year-old woman presented with a cutaneous lesion of the left fifth finger that had developed 10 years previously and had been diagnosed as eczema. The lesion had persisted in spite of multiple treatments with topical corticosteroid preparations. The patient's medical history included chronic bronchitis, hypertension, hypercholesterolemia, gastroesophageal reflux, diabetes mellitus and recurrent parathyroid adenomas. Current medications included dyphylline (Lufyllin), enalapril (Vasotec), lovastatin (Mevacor), ranitidine (Zantac) and insulin.

Cutaneous examination showed a 2 X 2 cm erythematous plaque with areas of overlying scale, located predominantly on the radial aspect of the dorsal and palmar surfaces of the left fifth finger (Figure 1). Fungal hyphae were not observed on a 10 percent potassium hydroxide preparation of scrapings from the lesion. The patient had no cutaneous lesions consistent with actinic atrophy, solar keratoses, basal cell carcinoma or squamous cell carcinoma.

A punch biopsy of the lesion was performed (Figure 2). Histologic examination of the epidermis demonstrated hyperkeratosis, acanthosis, and irregular elongation and thinkening of the rete ridges. Throughout the entire thickness of the epidermis, mitotic activity was increased, and atypical and pleomorphic keratinocytes were present. Dyskeratotic cells and occasional vacuolated keratinocytes were also noted in the epidermis. Telangiectatic vessels with perivascular lymphocytic infiltrates were seen in the papillary dermis. The dermoepidermal junction was well defined, and the abnormal keratinocytes had not invaded the dermis. These pathologic changes were consistent with Bowen's disease.

Surgical excision of the lesion with a full-thickness skin graft was performed.

History and Epidemiology

Cutaneous squamous cell carcinoma in situ is frequently referred to as Bowen's disease. The condition was initially reported in 1912 by Bowen, who described two men with "precancerous dermatoses" that were characterized by a chronic atypical epithelial proliferation. The term "Bowen's disease" first appeared two years later when additional cases were reported by Darier.

Bowen's disease occurs predominantly in older persons. Although the age range begins in the third decade, the mean age at diagnosis is in the sixth decade. [1-3] A slight preponderance of either men [4] or women [2] has been observed in studies of patients with Bowen' with Bowen's disease. Most reported cases have occurred in white persons, although the disease has also been reported in other racial groups. [3,5]

Etiology

The pathogenesis of Bowen's disease is probably multifactorial. Circumstantial

TABLE 1

Clinicopathologic Differential Diagnosis

of Bowen's Diasease

and laboratory evidence for certain etiologic agents has been reported. The development of Bowen's disease may be related to a gentic predisposition as reflected by race, skin type and possibly even subtle defects in DNA repair following exposure to ultraviolet radiation or chemicals. [1] Alternatively, the distribution of lesions on sun-exposed areas suggests the possibility that ultraviolet radiation may either initiate or promote the development of Bowen's disease. [5]

Inorganic arsenic has been etiologically associated with Bowen's disease. [1,5-7] This chemical was formerly present in several medications, such as "bromide" mixtures, Fowler's solution and Gay's solution, which were used for epilepsy, psoriasis and asthma, respectively. The chemical was also used in occupational agents, such as fungicides, pesticides and weed-killers, and could be found in well water.

Data also suggest that a viral factor may contribute to the pathogenesis of Bowen's disease. Human papillomavirus type 2, 16 and 34 have recently been identified in extragenital lesions of Bowen's disease. [8]

In several cases, a primary internal malignancy was detected before, at the same time or after the diagnosis of Bowen's disease. [4] The relationship of Bowen's disease to visceral cancer is uncertain, and whether an association exists is controversial. [4] Recently, the statistical methodology of published studies on this issue was reevaluated [9]; the meta-analysis revealed that the studies did not demonstrate an increased risk for the development of internal malignancy in persons with Bowen's disease. Thus, an extensive search for an internal malignancy is not indicated. [10]

Clinicopathologic Characteristics

Bowen's disease typically presents as an asymptomatic, scaly or crusted, erythematous plaque that is usually sharply delineated from the normal surrounding skin. The lesions most commonly occur on the head but may also appear on other areas of the body and mucosal surfaces. Both sun-exposed and nonexposed skin may be affected. [1,4]

Many conditions morphologically mimic Bowen's disease [1,5] (Table 1). In the illustrative case, the lesion had been present for 10 years, repeatedly diagnosed as dermatitis and unsuccessfully treated with topical corticosteroids. The interval between the development of lesions and diagnosis of Bowen's disease is often five to eight years. [1,2,4] Therefore, in patients with a persistent cutaneous lesion that is of uncertain diagnosis or that has been diagnosed clinically as "atypical" or "steroid-nonresponsive" dermatitis, the possibility of Bowen's disease should be considered and a lesional biopsy performed for histologic evaluation.

Rarely, Bowen's disease may present as a pigmented lesion. In black patients, who are less frequently affected than whites, the disease typically appears as pigmented, maculupapular lesions, which may clinically resemble several conditions [3] Table 1). Other diagnostic possibilities that should be considered before biopsy include granuloma faciale, lentigo maligna melanoma and seborrheic keratosis. [1,6]

In Bowen's disease, histopathologic examination demontrates full-thickness atypia of the keratinocytes, with increased mitotic activity and abnormal mitoses throughout the epidermis and extending into the epithelium of adnexal structures. In addition, the epidermis exhibits hyperkeratosis with parakeratosis, marked acanthosis and flattening of the elongated and thickened rete ridges. Epidermal cells that are multinucleated or that show atypical keratinization (dyskeratosis or apoptosis) are also common histologic features; occasionally, vacuolated cells are seen in the upper portion of the epidermis. [7,11] In the upper dermis, a moderate inflammatory infiltrate of mononuclear cells is present. Immunoperoxidase histochemical studies have shown these infiltrates to consist mainly of T lymphocytes, predominantly of the eT-helper-cell subset. [12]

Treatment and Prognosis

The therapy of choice for bowen's disease is surgical excision, which may be performed with either a scalpel or a laser. [13] For lesions that are recurrent, are located on mucous membranes or involve sites requiring the sparing of normal tissue, excision using Mohs microscopically controlled surgical technique has been recommended. [14]

Treatment with alternative modalities, such as electrodesiccation with curettage, cryotherapy and radiotherapy, has often been followed by recurrence of the original lesion. This probably occurs because, first, the extent to which the underlying follicular or sweat duct structures re involved is impossible to predict and, second, the atypical epidermis within the depths of these appendageal structures is not completely destroyed. Similarly, although topical application of 5 percent 5-fluorouracil cream has also been recommended for the treatment of Bowen's disease, [15] recurrence has been reported following such treatment. [5]

Bowen's disease is regarded as a premalignant condition. Even though the lesion is often present for several years before diagnosis, the abnormal keratinocytes are confined to the epidermis and the condition represents a squamous cell carcinoma in situ, which can be cured with appropriate intervention. If the lesions of Bowen's disease remain untreated, invasive squamous cell carcinoma--with the potential for metastasis--may develop in approximately 2 to 5 percent of patients. [5,7]

REFERENCES

[1] Lee MM, Wick MM. Bowen's disease. CA 1990;40:237-42.

[2] Thestrup-Pedersen K, Ravnborg L, Reymann F. Morbus Bowen. A description of the disease in 617 patients. Acta Derm Venereol 1988; 68:236-9.

[3] Mora RG, Perniciaro C, Lee B. Cancer of the skin in blacks. III. A review of nineteen black patients with Bowen's disease. J Am Acad Dermatol 1984;11(4 Pt 1):557-62.

[4] Callen JP, Headington J. Bowen's and non-Bowen's squamous intraepidermal neoplasia of the skin. Relationship to internal malignancy. Arch Dermatol 1980;116;422-6.

[5] Gard D. Nonpigmented premalignant lesions of the skin. Clin Plast Surg 1987;14;413-23.

[6] Ragi G, Turner MS, Klein LEm Stoll HL Jr. Pigmented Bowen's disease and review of 420 Bowen's disease lesions. J Dermatol Surg Oncol 1988;14:765-9.

[7] Brownstein MH, Rabinowitz AD. The precursors of cutaneous squamous cell carcinoma. Int J Dermatol 1979;18:1-16.

[8] Kettler AH, Rutledge M, Tschen JA, Buffone G. Detection of human papillomavirus in nongenital Bowen's disease by in situ DNA hybridization. Arch Dermatol 1990;126:777-81.

[9] Lycka BA. Bowen's disease and internal malignancy. A meta-analysis. Int J Dermatol 1989;28-531-3.

[10] Callen JP. Bowen's disease and internal malignant disease. Arch Dermatol 1988;124-675-6.

[11] Strayer DS, Santa Cruz DJ. Carcinoma in situ of the skin: a review of histopathology. J Cutan Pathol 1980;7:244-59.

[12] Habets JM, Tank B, van Joost T. Characterization of the mononuclear infiltrate in Bowen's disease (squamous cell carcinoma in situ). Evidence for a T cell-mediated anti-tumour immune response. Virchows ARch [A] 1989;415:125-30.

[13] Mikhail GR. Cancers, precancers, and pseudocancers on the male genitalia. A review of clinical appearances, histopathology, and management. J Dermatol Surg Oncol 1980;6:1027-35.

[14] Brown MD, Zachary CB, Grekin RC, Swanson NA. Genital tumors: their management by micrographic surgery. J Am Acad Dermatol 1988:18(1 Pt 1):115-22.

[15] Sturm HM. Bowen's disease and 5-fluorouracil. J Am Acad Dermatol 1979;1;513-22.

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