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Bowen's Disease

Bowens Disease

Bowen's disease is a type of squamous cell carcinoma. This epidermal neoplasm is growing in situ, and it is usually of reddish-brown color, covered by scales or crusts.


Presentation

According to retrospective studies conducted in Europe and Australia, BD most commonly affects the face, the lower legs, neck and upper limbs [7]. Typical lesions are characterized by their reddish-brown color and appear as erythematous, scaly or crusted patches or plaques; they are generally well demarcated. Pigmentation is not common, but about 2% of BD patients present increased amounts of melanin pigment in the epidermis or papillary dermis [10]. This entity is known as pigmented BD. Patients may refrain from seeking medical attention until cutaneous lesions reach several centimeters in diameter because they are commonly painless. Pruritus, hemorrhages and purulent discharge are rarely observed but may result from trauma and secondary bacterial infection.

In rare cases, BD may affect the nails, the genital or perianal region (primarily as penile BD), or mucous membranes. Tumors have been reported not to respect the anatomical boundaries of the respective organ and may or may not comprise adjacent skin. The clinical picture of nail BD is very heterogenous and may mimic onychomycosis, paronychia and other nail disorders [11]. BD affecting mucous membranes largely resemble classical BD, but have a smooth or velvety surface.

Neglect
  • One patient was more concerned about the lesion, whereas the other patient neglected the lesions, though widespread. High index of suspicion is required to diagnose such atypical presentations of Bowen's disease.[ncbi.nlm.nih.gov]
  • The concern is that Bowen's disease can eventually develop into a different type of skin cancer called squamous cell skin cancer if it's left undiagnosed or neglected.[nhs.uk]
  • Because interdigital BD can be misdiagnosed due to the benign appearance of the tumour, a neglect of the lesion can contribute to progress to invasive carcinoma.[omicsonline.org]
Genital Lesions
  • The risk of progression into an invasive carcinoma is 3-5% in extragenital lesions and about 10% in genital lesions. We present two cases of Bowen's disease where the pattern, size, and perception of the disease between the patients varied.[ncbi.nlm.nih.gov]
  • lesions and 10% in genital lesions. [2] A 57-year-old man presented with a painless raised lesion over the shaft of penis since five years, which was gradually increasing in size.[idoj.in]
  • The risk of progression to invasive SCC is 3–5 % for extragenital lesions and 10 % for genital lesions. BD is very common in the Caucasian population with an incidence of 14 per 100,000 in some populations.[link.springer.com]
  • Mohs micrographic surgery 31 This is an excellent method for larger lesions, poorly demarcated lesions, recurrent lesions on the head and neck, or areas where tissue sparing is vital, such as digital or genital lesions.[dermaamin.com]

Workup

Because BD is associated with non-specific signs and symptoms, grows slowly and doesn't interfere with everyday life, diagnostic delays of several years after initial presentation are not uncommon. In fact, many BD patients present with a medical history of "intractable" tinea corporis or psoriasis. Here, skin biopsy specimens have to be obtained. It is recommended to sample distinct sites, particularly in extensive lesions, to avoid overlooking a possible infiltration of dermal layers. For smaller lesions, diagnostic biopsy and definitive excision may be carried out in one single procedure. Histopathologically, BD is characterized by the following features:

  • Epidermal hyperplasia and dysplasia, single layers may be difficult to distinguish due to a loss of polarity
  • Parakeratosis and hyperkeratosis
  • Numerous mitotic figures at all levels
  • Nuclear pleomorphism
  • Vacuolization
  • Atypical cells may be observed in sweat glands, sebaceous glands and follicular epithelium
  • Stratum basale unaltered
  • Dermal hyperemia
  • Clusters of tumor cells infiltrating the dermis as well as desmoplasia are untypical for BD

Immunohistochemical analyses may be helpful to differentiate BD from other (pre-)malignant neoplasms that may affect the skin, e.g., extramammary Paget disease, keratoacanthoma, squamous cell carcinoma and melanoma. Tumor cells of BD stain positive for p63; distinct results have been reported for cytokeratin 10 staining [12] [13].

Treatment

There are distinct approaches to BD therapy [2]. Elliptical excision of cutaneous lesions is most frequently performed [14], but may not be indicated for extensive neoplasms, multiple lesions and tumors affecting face, digits, genitals or other areas of the body that don't allow for the necessary surgical margin. Here, Mohs micrographic surgery may be applied. This technique enables the surgeon to reduce margins as far as possible, since excised tissue is immediately analyzed for the presence of tumor cells by means of frozen section histology. Shave excision and cryotherapy as well as curettage and electrofulguration may also be carried to treat BD, but cryotherapy has occasionally been reported to be associated with high recurrence rates.

With regards to medication, 5-fluorouracil has been applied topically to inhibit tumor cell proliferation. Because BD is generally restricted to the epidermis, penetration of the agent into deeper layers of the skin is usually not required.However, follicular epithelium may be affected and may serve as a reservoir for tumor cells after cessation of therapy. Imiquimod may be used similarly, although the precise antineoplastic mechanism of this immunomodulator is not yet understood. 5-aminolevulinic acid or methyl aminolevulinate with photodynamic therapy has been carried with varying degrees of success [3].

Neither therapy excludes the possibility of recurrence and thus, patients should undergo annual follow-ups. Biannual re-evaluation is indicated in patients with higher risks of skin cancer, i.e., in those individuals who presented with multiple BD, recurrent BD or immunosuppression.

Prognosis

In general, BD patients have an excellent prognosis. Lesions are usually painless, slow-growing and respond well to therapy. If left untreated, a small percentage of in situ carcinomas may transition to skin cancer. Although the disease will follow this course in no more than 3% of cases, invasive squamous cell carcinoma is associated with significant morbidity and mortality [2]. To date, it is not known whether this slightly increased risk of skin cancer does result from inherent properties of cells that form the pre-malignant neoplasm, or if it is rather the consequence of common risk factors like sun exposure [9]. Of note, an increased risk of transition to malignant neoplasms has been reported for immunocompromised patients diagnosed with actinic keratosis [4] and because both disease share several common features, it may be speculated that this also applies for BD.

Etiology

The precise trigger of BD is unknown and a multifactorial etiology is currently assumed for this disease. Because BD primarily affects sun-exposed areas of the skin, prolonged and/or accumulated sun exposure have repeatedly been proposed as risk factors [3]. This hypothesis is in agreement with the fact that ultraviolet radiation has long since been recognized as carcinogenic. Moreover, BD incidence increases with age and people of light complexion are affected more frequently than individuals with dark skin. Besides sun exposure, pre-existing skin disorders and immunodeficiency have been related to the development of in situ squamous cell carcinoma. With regards to the former, several case reports exist that relate BD human papillomavirus (HPV) infection and actinic keratosis with BD. These conditions may be mutually dependent and share common causes. Actinic keratosis, for instance, has also been associated to HPV infection, and is more likely to transition to invasive squamous cell carcinoma in immunocompromised patients [4]. According to a recent publication, HPV may play a crucial role in the development of genital BD, since HPV prevalence in genital BD has been shown to exceed 66%, while only 8% of extra-genital specimens have tested positive for these pathogens [5]. HPV types 6, 16, 33, 52, 56, 58 and 59 have been encountered in this study, but elsewhere, additional types have been described in BD patients. Nevertheless, cutaneous lesions predisposing for BD are not restricted to infectious and neoplastic diseases, but may also include physical and chemical noxious agents as well as irradiation.

Epidemiology

Available data regarding the incidence and prevalence of BD vary largely and range from 14 to 140 per 100,000 inhabitants [6]. Epidemiological studies published to date agree in that Caucasians living in geographic areas of high solar radiation are most susceptible to the disease. Considering these observations, it is not surprising that highest incidence rates have been reported in Hawaii. A more recent study comparing demographic data of BD patients in the United Kingdom and Australia yielded similar results [7]. Of note, predilection for fair skin is not observed in BD patients who present with lesions in areas that are not exposed to the sun, e.g. in cases of genital BD. In sum, BD is presumably underdiagnosed: The disease preferentially affects people aged 70 years and older and is not associated with acute symptoms that reduced life quality. With respect to gender, males and females are equally affected by BD.

Sex distribution
Age distribution

Pathophysiology

BD is a neoplastic disorder generally restricted to the epidermis. However, a small percentage of BD may progress to skin cancer. Ulceration of cutaneous lesions, hemorrhages, induration and the formation of a palpable nodule are indicative of malignant transformation and invasive growth [8]. In order to avoid such complications, tumors should be treated accordingly.

Prevention

Prolonged sun exposure is a major risk factor for BD. Consequently, protective clothing, use of sunscreen and reduction of overall sun exposure may help to decrease the individual risk of the disease. Furthermore, patients at risk should undergo regular dermatological screens.

Summary

Bowen's disease (BD) is a neoplastic skin disorder that has first been described by John Templeton Bowen, a US-American dermatologist, at the beginning of the last century [1]. Affected individuals develop a squamous cell carcinoma which is growing in situ, i.e., it usually does not infiltrate extra-epidermal tissues. However, it may spread laterally and reach considerable extensions. It is generally well-demarcated, of reddish-brown color, scaly or crusted.

Due to its appearance, BD is easily confounded with skin infections, dermatitis or psoriasis. Histopathological analyses of skin biopsy specimens are thus required to confirm the diagnosis, and they frequently reveal properties that don't allow for a clear distinction between a benign neoplasm and cancer: Prominent epidermal hyperplasia with numerous mitotic figures, nuclear anomalies and keratin pearls would indeed suggest a malignant process, and these features are displayed by all epidermal layers with the exception of the stratum basale. However, the basal layer of the epidermis clearly separates the neoplasm from underlying tissues, with only signs of an enhanced blood flow being noteworthy with regards to the dermis. Agglomerations of atypical cells that would indicate an infiltration of deeper layers of the skin are absent.

BD patients may present with solitary or multiple lesions. Because affected individuals are at risk of developing malignant, invasive skin cancer, in situ neoplasms should be treated [2]. Standard treatment regimens are highly successful in BD patients.

Patient Information

Bowen's disease (BD) refers to an epidermal neoplasm growing in situ, i.e., tumor cells are only observed in the outer layer of the skin, may grow to considerable dimensions within the epidermis, but don't penetrate deeper tissues. In this context, BD is generally considered a pre-malignant disorder that shows properties of both benign tumors and skin cancer. Transition to malignant skin cancer is rare, but has been shown to occur in about 3% of cases. Therefore, BD should be treated in an appropriate manner even though it does usually not interfere with day-to-day activities: BD manifests in form of patches or plaques of reddish-brown color that are covered by scales or crusts. They are usually neither painful nor itchy. Most of these tumors develop in sun-exposed areas of the skin, namely in the face and neck region, lower legs, and arms. Patients may develop solitary or multiple lesions. In order to confirm a tentative diagnosis of BD, skin biopsy specimens have to be obtained and analyzed histopathologically. In case of small lesions, outright excision and subsequent examination of this tissue sample comprises a diagnostic and therapeutic measure. In fact, elliptical excision is the most common form of treatment. Other options may be considered if the extension and localization of the tumor doesn't agree with this technique. Here, micrographic surgery, curettage and electrofulguration, cryotherapy or photodynamic therapy may be indicated. There are also antineoplastic agents that may be applied topically. In most cases, BD patients respond very well to therapy. Their prognosis is excellent.

References

Article

  1. Weyers W. The centennial of Bowen's disease-a critical review on the occasion of the 100th anniversary of its original description. Dermatol Pract Concept. 2012; 2(4):204a202.
  2. Bath-Hextall FJ, Matin RN, Wilkinson D, Leonardi-Bee J. Interventions for cutaneous Bowen's disease. Cochrane Database Syst Rev. 2013; (6):Cd007281.
  3. Maury G, Girard C, Michot C, Guillot B, Dereure O. [Multiple Bowen disease of the lower limbs in elderly women: a rare clinical subset involving therapeutic difficulties]. Ann Dermatol Venereol. 2009; 136(6-7):508-512.
  4. Majores M, Bierhoff E. [Actinic keratosis, Bowen's disease, keratoacanthoma and squamous cell carcinoma of the skin]. Pathologe. 2015; 36(1):16-29.
  5. Murao K, Yoshioka R, Kubo Y. Human papillomavirus infection in Bowen disease: negative p53 expression, not p16(INK4a) overexpression, is correlated with human papillomavirus-associated Bowen disease. J Dermatol. 2014; 41(10):878-884.
  6. Reizner GT, Chuang TY, Elpern DJ, Stone JL, Farmer ER. Bowen's disease (squamous cell carcinoma in situ) in Kauai, Hawaii. A population-based incidence report. J Am Acad Dermatol. 1994; 31(4):596-600.
  7. Morley GL, Matthews JH, Verpetinske I, Thom GA. A Comparative Study Examining the Management of Bowen's Disease in the United Kingdom and Australia. Dermatol Res Pract. 2015; 2015:421460.
  8. Morton CA, Birnie AJ, Eedy DJ. British Association of Dermatologists' guidelines for the management of squamous cell carcinoma in situ (Bowen's disease) 2014. Br J Dermatol. 2014; 170(2):245-260.
  9. Jaeger AB, Gramkow A, Hjalgrim H, Melbye M, Frisch M. Bowen disease and risk of subsequent malignant neoplasms: a population-based cohort study of 1147 patients. Arch Dermatol. 1999; 135(7):790-793.
  10. Lee JW, Hur J, Yeo KY, Yu HJ, Kim JS. A Case of Pigmented Bowen's Disease. Ann Dermatol. 2009; 21(2):197-199.
  11. Wollina U. Bowen's disease of the nail apparatus: a series of 8 patients and a literature review. Wien Med Wochenschr. 2015; 165(19-20):401-405.
  12. Ishida H, Kumakiri M, Ueda K, et al. Comparative histochemical study of Bowen's disease and actinic keratosis: preserved normal basal cells in Bowen's disease. Eur J Histochem. 2001; 45(2):177-190.
  13. Boer-Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease. J Cutan Pathol. 2012; 39(2):225-233.
  14. Hansen JP, Drake AL, Walling HW. Bowen’s Disease: a four-year retrospective review of epidemiology and treatment at a university center. Dermatol Surg. 2008; 34(7):878-883.

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Last updated: 2019-07-11 22:02