Bowen's disease

Bowen's disease Microchapters
Overview
Historical Perspective
Pathophysiology
Causes
Epidemiology and Demographics
Natural History, Complications and Prognosis
Diagnosis
Treatment
Prevention
Differentiating Bowen's disease from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[2], Jesus Rosario Hernandez, M.D. [3]

Synonyms and keywords: Bowen's carcinoma; squamous cell carcinoma in situ of skin; intraepidermal carcinoma skin, Intraepithelial neoplasia

Overview

In medicine (dermatology), Bowen's disease (BD) is a sunlight-induced skin disease, classified either as an early noninvasive stage or intraepidermal form of squamous cell carcinoma which if left undiagnosed, untreated, or neglected has <10% chance of malignant transformation into invasive squamous cell carcinoma of the skin. It usually appears as a erythematous, scaly or crusty patch or plaque anywhere on the body but most commonly involves lower legs, with other possible sites of involvement to be head, neck, genitals, and skin folds. It is easily curable by various treatment options such as cryotherapy, curettage, cautery, photodynamic therapy, topical chemotherapy, radiotherapy, or excision of the lesion.

Historical Perspective

• In 1912, Dr John T. Bowen was the first one to describe this disease, hence, it is named after him

Pathophysiology

Microscopic Pathology

• Cells in Bowen's disease are extremely unusual or atypical under the microscope
• In many cases, cells look worse under the microscope than the cells of many outright and invading squamous cell carcinomas
• Degree of atypia (strangeness, unusualness) seen under the microscope best tells how cells may behave (should they invade another portion of the body)

Borst-Jadassohn phenomenon

• Bowen's disease can also occur as a part of Borst-Jadassohn phenomenon (previously known as intraepidermal epithelioma) which is a heterogeneous group of following intraepithelial lesions:
  • Irritated seborrheic keratosis
  • Clonal seborrheic keratosis
  • Eccrine poroma
  • Malignant eccrine poroma
  • Intraepithelial neoplasia (Bowen's disease)
  • Other intraepidermal sweat gland tumors

H & E stain ofBowen's disease as seen under a microscope [https://commons.wikimedia.org/wiki/Category:Histopathology_of_Bowen%27s_disease#/media/File:Bowen_disease_(2).jpg Source: Wikimedia Commons

Histopathology of squamous cell carcinoma in situ of the skin (Bowen disease). H & E stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_Bowen%27s_disease#/media/File:Bowen_disease_(3).jpg Source: Wikimedia Commons

Bowen's disease as seen under a microscope

Histopathology of squamous cell carcinoma in situ of the skin (Bowen disease). H & E stain [https://commons.wikimedia.org/wiki/Category:Histopathology_of_Bowen%27s_disease#/media/File:Bowen_disease_(4).jpg Source: Wikimedia Commons

SCCIS from sundamaged skin. Pagetoid SCCIS on the left, conventional SCCIS on the right. [https://commons.wikimedia.org/wiki/Category:Histopathology_of_Bowen%27s_disease#/media/File:Skin_SCCIS_PagetoidandConventional_15BR30103.jpg Source: Wikimedia Commons

Squamous cell carcinoma in situ or Bowen disease[https://commons.wikimedia.org/wiki/Category:Histopathology_of_Bowen%27s_disease#/media/File:SkinTumors-P5280074.JPG Source: Wikimedia Commons

Causes

Bowen's disease is a non-infectious, non-familial disease with common causes as mentioned below:

• Solar damage due to long-term sun exposure or use of sunbeds, especially in people with fair skin
• Aging
• Carcinogens such as arsenic:
  • Used in manufacturing industry and for other commercial uses
  • 10 years or so after the initial exposure to arsenic are required before it causes Bowen's disease
  • Well water once used in various medical preparations was known to have been contaminated with arsenic in past
• Weak immune system due to:
  • Immunosuppressants after organ transplant
  • AIDS
• Viral infection such as:
  • Different types HPV/human papillomavirus:
    • HPV 16, 18, 34, and 48 are associated with Bowen's disease of perianal & genital region especially bowenoid papulosis and VIN are caused by HPV 16
    • HPV 2, 16, 34, and 35 are associated with Bowen's disease in other areas of body (excluding genitals)
    • 47% of acral and 24% of nonacral extragenital Bowen's disease lesion contains HPV genome
  • Merkel cell polyomavirus
• Previous irradiation such as:
  • Ultraviolet irradiation
  • Radiotherapy treatment
  • Photochemotherapy
• Chronic skin injury
• Dermatoses
• Sjögren's syndrome

Epidemiology and Demographics

Age

• Bowen's disease can affect adults of any age, most commonly involves older patients in their 60s or 70s
• It is rare before the age of 30 years

Gender

• Bowen's disease occurs more predominantly in men than in women (70-85% of cases)

Race

• Caucasians are the ones most commonly affected by Bowen's disease

Natural History, Complications and Prognosis

• Bowen's disease grows very slowly over the period of months or even years
• It is easily treatable if diagnosed in time
• If left undiagnosed, untreated or neglected, Bowen's disease can ultimately progressively develop into invasive squamous cell carcinoma of the skin in 1 in 20-30 people (i.e. 3-5% risk)
• SCC is a treatable condition, but if it's deeper or invasive, it means it's very serious

Diagnosis

Common symptoms

• It usually appears as one or more skin patches with following characteristics:
  • Persistent
  • Progressive
  • Non-elevated
  • Non-healing
  • Irregular clear edges
  • Scaly
  • Crusty
  • Red or pink
  • Warty (verrucous)
  • Upto a few centimetres across (larger than half-inch wide)
  • Flat or raised
  • Oozing of pus
  • Itchy (but not all the time)
  • Splits open (fissured)
  • Darkly colored (pigmented)

Signs and symptoms of malignant transformation

• Following changes in the skin patch are the signs that bowen's disease has turned into invasive squamous cell carcinoma of the skin:
  • Easy bleeding
  • Tenderness
  • Turns into an open sore i.e. ulcerates
  • Hardening (induration)
  • Develops into a lump/fleshy nodule

Common sites of involvement

• Common sites involved are:

Skin

• Lesions can occur anywhere on the skin surface or on mucosal surfaces, although the involvement of palms or soles is uncommon
• A persistent progressive non-elevated red scaly or crusted plaque which is due to an intradermal carcinoma and is potentially malignant
• Atypical squamous (resembling fish scales) cells proliferate through the whole thickness of the epidermis

Bowen disease.Source: Dermatology Atlas

Bowen disease.Source: Dermatology Atlas

Bowen disease.Source: Dermatology Atlas

Bowen disease.Source: Wikimedia Commons

Extremities

• About three-quarters of the patients have lesions on the lower leg (60-85%), usually in previously or presently sun-exposed areas of skin

Head and neck area

• Being prone to the sun exposure, head and neck area is also one of the common sites to be affected by Bowen's disease

Bowen disease. Source: Wikimedia Commons

Bowen disease. Source: Wikimedia Commons

Bowen disease. Source: Wikimedia Commons

Subungal, periungal region

• Bowen's disease also commonly involves subungal or periungal areas (i.e. either under or around fingernails or toenails)

Skinfolds

Bowen disease. Source: Dermatology Atlas

Genitourinary system

• Bowen's disease can also involve genital and perianal areas
• It appears in following 3 forms in genital area:

Multiple forms of Bowen's disease involving genital region

Bowen's disease form	Characteristic features
Bowenoid papulosis	Affects both men and women Lesions can last from 2 weeks to several years
Erythroplasia of Queyrat	Affects tip of the penis (glans penis-outer keratinized surface of the penis) Occurs in middle-aged uncircumscribed men due to unknown reasons May cause any of the following: Reddish, velvety or smooth plaque Ulcers Discharge Bleeding Itching Scaling Crusting Difficulty urinating Dysuria Also known as Bowen's disease of the glans penis
Vulvar intraepithelial neoplasia (VIN)	Affects vulva in women Causes bright red, velvety, patches that severely itch or burn in women Associated with HPV 16

Bowen disease.Source: Dermatology Atlas

Bowen disease.Source: Dermatology Atlas

Physical Examination

• Bowen's disease typically presents as a gradually enlarging, well demarcated erythematous plaque with an irregular border and surface crusting or scaling
• Lesion might feel tender representing its malignant transformation

Bowen's disease Klaus D. Peter, Gummersbach, Germany, CC BY 3.0 de

Bowen's disease

Dermoscopy

• Dermoscopy is the skin examination via skin surface microscopy
• Also known as:
  • 'Epiluminoscopy'
  • 'Epiluminescent microscopy'
• It is usually used for examination of pigmented skin lesions
• Benefits of dermoscopy include:
  • Improvement of diagnostic accuracy of pigmented skin lesions
  • Evaluation of nonpigmented skin tumors (recognizes vascular structures not visible to naked eye)
  • Helpful in diagnosis of Bowen's disease and shows:
    • Repetitive morphological findings such as glomerular vessels and scaly surface
    • Small brown globules and/or homogeneous pigmentation in case of pigmented Bowen's disease

Skin biopsy

• Skin biopsy must be done to:
  • Confirm the diagnosis Bowen's disease
  • Differentiate from other skin lesions
  • Rule out invasive squamous cell carcinoma of the skin

Treatment

• Specific treatment for an individual case depends upon various factors, such as:
  • Affected body site
  • Size
  • Thickness of the lesion(s)
  • Number of the lesion(s)
  • Presence or absence of certain symptoms
  • Patient’s age
  • Patient's general health
  • Possible side effects of the treatment
  • Possible long term effects of the treatment
  • Patient's preference
• Different treatment options for Bowen's disease include the following:

Different treatment options for Bowen's disease

Treatment option	Details
Watch and wait	Patient with a slow-growing disease is followed up without any treatment given until the disease progression occurs Done in elderly patients having a slowly growing lesion in poor healing area such as lower leg
Cryosurgery/Freezing	Cells of the lesion are destroyed by freezing them with either liquid nitrogen or argon gas Later on, the dead tissue sloughs off on thawing within few weeks Favored by some clinicians over excision Mostly effective for single or small lesions
Topical cream	Includes following 2 options: 5% Imiquimod cream Chemotherapy cream (5-fluorouracil) Favored by some clinicians over excision Cream needs to be applied once or twice for atleast two weeks if not longer
Curettage & electrodesiccation or cryotherapy	Affected skin area is scraped away under local anaesthetic (which numbs the skin) using a device having a circular blade (curet) Then an electric current is passed through the remaining of the lesion via an electric needle which destroys any of the remaining cells Liquid nitrogen can be used in order to freeze the base and edges of the treated area
Cauterization or diathermy coagulation	After scraping the affected area, cautery is applied to the remaining of lesion and to stop any bleeding
Photodynamic therapy (PDT)	Uses combination of laser light and drugs making affected cells sensitive to light to destroy affected skin cells One treatment session lasts for 20-45 minutes More than one sessions might be required
Radiation therapy	High-powered energy beams such as X-rays are used to kill affected cells Two types of radiation therapy can be used: External radiation therapy (a machine outside the body is used to send radiation towards the diseased cells) Internal radiation therapy (radioactive substance is used which is sealed in needles, seeds, wires, or catheters which are placed directly into or near the lesion)
Excision	It includes cutting off the affected tissue with a surrounding margin of healthy skin under local anesthetic and might require stitches afterwards Highly successful Complications include surgical scar
Mohs micrographic surgery	Uses special training & technique involving the skin removal, layer by layer with subsequent examination of each layer under microscope, until no abnormal cells are remaining Least amount of the surrounding healthy tissue is removed Edges are immediately checked to see if tumor is found Provides best cosmetically favorable results especially on the skin areas with: Recurrent lesions of head and neck region with limited excess skin such as face Larger lesions Lesions involving the areas requiring as much tissue preservation as possible such as around the nail Highest cure rate among all the available treatment options

Prevention

Following are the few preventive measures to lower the risk for developing Bowen's disease:

Primary preventive measures for Bowen's disease

Preventive method	Details
Avoiding sunburns and suntans	Avoid sun exposure: During the middle of the day, usually from 10 AM to 4 PM, especially in North America Even during cloudy days or winters
Wearing protective clothing	Wear the following while being in the outdoor environment: Tightly woven, dark clothing Shirts with long sleeves Broad-brimmed hats Pants that fully cover the legs (avoid shorts) Photoprotective clothing Sunglasses (the ones which block both types of UV radiation i.e. UVA & UVB)
Wearing SPF sunscreen	Wear a sunscreen generously year-round, even during winters & cloudy days It should be at least SPF 30 It should be broad-spectrum blocking both UVA and UVB rays Cover all the exposed areas including the back of hands, neck, lips, tip of ears Reapply it every 2 hours & more often after swimming or if perspiring a lot
Avoiding tanning beds	Tanning beds use the lights that emit UV rays which can increase the risk for developing Bowen's disease
Being aware of sun-sensitizing medications	Over-the-counter drugs and common prescriptions including antibiotics may have tendency to increase the sensitivity of skin Always ask the doctor or pharmacist about the possible side effects of any medications before taking them Take extra precautions to protect the skin by staying away from the sun,in case if the medications being used have tendency to increase the skin sensitivity to sunlight
Checking skin regularly and reporting any new or unusual skin changes to the doctor	Examine the skin often for any new skin growths or changes in existing bumps,patches or plaques Check face, ears, neck, and scalp by using the mirror Examine the chest, trunk, top & underside of arms and hands Examine both the front and back of legs, and feet, including soles and spaces between the toes Also check the genital area and area between the buttocks
Reducing the exposure to ultraviolet (UV) radiation, especially during the early years of life	Prior history of radiation exposure (both UV or artifical radiation therapy for acne or eczema) leads to increased chance for development of Bowen's disease

Differentiating Bowen's disease from other Diseases

• Bowen's disease must be differentiated from the following:
  • Psoriasis
  • Eczema
  • Superficial basal cell carcinoma
  • Actinic keratosis
  • Seborrheic keratosis
  • Lichen planus
  • Tinea corporis
  • Extramammary Paget’s disease

Differentiating Bowen's disease from other diseases

Disease entity	Etiology	Pathophysiology	Common sites of involvement	Clinical manifestations	Images
Bowen's disease	Common causes include: Solar damage Aging Arsenic Immunosuppression (after organ transplant, AIDS) HPV Merkel cell polyomavirus Irradiation (UV irradiation, photochemotherapy, radiotherapy) Chronic skin injury Dermatoses Sjogren's syndrome	Histopathology shows: Unusual or atypical cells Borst-Jadassohn phenomenon	Most commonly involves: Lower legs Head and neck area Skin folds Perianal and genital area Subungal and periungal area	Appears as one or more persistent, non-healing, non-elevated, scaly or crusty, itchy, erythematous patches or plaques Signs of malignant transformation of the lesion include bleeding, ulceration, induration, tenderness, fleshy bump	Bowen's disease
Psoriasis	PSORS-1 (part of the major histocompatibility complex) on chromosome 6p2, is the major genetic determinant of psoriasis Environmental factors implicated in the development or aggravation of psoriasis are: Stress (physical and mental) Smoking Excessive alcohol consumption Infection (Streptococcal, HIV) Seasonal variation Medications (lithium, beta blockers, pegylated interferon alpha-2b, siltuximab) Obesity Skin injury Skin dryness	Histopathology shows: Hyperkeratosis Parakeratosis Munro's microabscess Kogoj pustules Dermal infiltration with mononuclear cells mainly myeloid and T cells Capillary loop dilation (causes red appearance of psoriatic lesions)	Involves: Extensor surfaces like elbows and knees Scalp Lumbosacral area	Red or salmon-colored well-defined plaques with silvery-white dry scaling Pain described as unpleasant, burning, itchy, hot Pruritis High fever Dystrophic nails Arthralgia Conjunctivitis or blepharitis Enthesitis Depression Dactylitis Geographic tongue	A young man whose back and arms are affected by psoriasis, source: wikipedia.org
Eczema	Common causes include: Netherton’s syndrome/ Congenital erythroderma characterized by mutations in SPINK5 gene which produces LEKTI, a protease inhibitor providing protection against damage caused by allergens Mutations in gene producing filaggrin protein (prevents skin dryness and provides physcial barrier of skin) Associated with other atopic diseases such as: Asthma Allergic rhinitis Hay fever Food allergy Urticaria Allergens such as: Pollens Animal dander Mold Cigarette smoke Dust mites Weather changes Stress (physical, mental, emotional) Hyper IgE syndrome (Job syndrome) Phenylketonuria Wiskott-Aldrich syndrome	Autoimmune mediated type 1 hypersensitivity reaction caused by allergens such as pollens, animal dander, mold, cigarette smoke, dust mites etc leading to skin inflammation	Involves: Flexor surfaces such as insides of elbows, wrist creases, back of knees Exposed skin surfaces such as face, hands, feet Infants have rash on face and scalp	Dry, scaly, erythematous skin rash Itching (worst at night) Blistering Peeling of skin Lichenification of skin (leather like) Depression Social anxiety	Typical, mild dermatitis
Superficial basal cell carcinoma	Common causes include: Radiation exposure(sunlight (UV light), tanning beds, and x-rays) TP53 gene mutations Inappropriate activation of the hedgehog signaling pathway (loss-of-function mutations in tumor-suppressorprotein patched homologue 1 (PTCH1) Gain-of-function mutations in sonic hedgehog (SHH), smoothened (SMO) Xeroderma pigmentosum Epidermodysplastic verruciformis Nevoid basal cell carcinoma syndrome Bazex Syndrome Rombo syndrome	Multiple lobular foci of basaloid palisading keratinocyte tumors These are usually attached superficially to the epidermis with a myxoid stroma and band-like lichenoid infiltrate	Most commonly involves the trunk Can also involve head, neck, and face	Well-circumscribed,erythematous, thin plaque or patch with scaling Central clearing and thin rolled borders	Kelly Nelson (Photographer) [Public domain], via Wikimedia Commons,https://upload.wikimedia.org/wikipedia/commons/3/32/Basal_cell_carcinoma%2C_superficial.jpg
Actinic keratosis	Solar damage caused by constant repeated sun exposure in fair-skinned individuals	Constant repeated sun exposure causes dry, thick, scaly, or crusty bumps Growths start out as flat scaly areas, and later grow into a tough, wart-like area	Can involve any sun-exposed area such as: Face Ears Neck Scalp Chest Back of hands Forearms Lips	Scaly, crusty, dry, thick growths or bumps which are dark or light, tan, pink, red, a combination of all of these	Actinic keratosis Source: Professor Peter Anderson DVM PhD
Seborrheic keratosis	Associated with activating mutations of a gene coding for a growth factor receptor (FGFR3)	Increased cell replication and proliferation	Involves: Face Chest Shoulders Back	Round or oval waxy growths resemblingflattened or raised warts, giving the appearance as if they were dripped onto the skin by a candle Exhibit a variety of colors, from pink or yellow through light tan, brown and black "Pasted-on" appearance Localized infection Excessive itching due to irritation caused by jewelry or clothing Size varies from very small to more than 1 inch (2.5 centimeters)	Gross natural color photo of face with multiple typical lesions Source: Professor Peter Anderson DVM PhD, University of Alabama at Birmingham, Department of Pathology
Lichen planus	Causes include: Allergic reaction tomedications for high blood pressure, heart disease and arthritis such as bendrofluazide, chloroquine, gold salts, hydrochlorothiazide, mepacrine, methyldopa, methyldopate, penicillamine Chronic hepatitis C virus infection Chronic graft-versus-host disease of the skin Stress Heart disease Lichen planopilaris Lichen ruber moniliformis	Hyperparakeratosis with thickening of the granular cell layer Development of a "saw-tooth" appearance of the rete pegs Degeneration of the basal cell layer Infiltration of inflammatory cells into the subepithelial layer of connective tissue	Involves: Sites are near wrist and ankle Scalp (lichen Planopilaris) Oral mucous membrane	Well-defined rash well-described by the "5 P's": Pruritic Planar Purple Polygonal Papules	Lichen planus
Tinea corporis	Caused by a tiny fungus known as dermatophyte Risk factors for acquiring this fungal infection include: Petting or grooming animals such as dogs, cats, horses, pigs, ferrets and cows Touching inanimate objects such as personal care products, bed linen, combs, athletic gear, or hair brushes contaminated by an affected person Living in crowded, humid conditions Excessively sweating Participating in close contact sports like soccer, rugby, or wrestling Wearing tight, constrictive clothing with poor aeration Weakened immune system (HIV infection or taking immunosuppressive drugs)	Fungal skin infection caused by ringworm/dermatophytes Fungi inhabit the nonliving, cornified layers of the skin, hair, and nail (attractive and conducive for fungal proliferation due to moist, warm environment) After 1-3 weeks of incubation period, dermatophytes invade peripherally in a centrifugal pattern Increased epidermal cell proliferation occurs in active border with resultant scaling in response to infection	Arms especially armpits in people who sweat excessively Legs Groin creases Skin folds of abdomen Hair Nails	Enlarging, raised red rings with a central area of clearing (ringworm) Scaly, elevated edges of rash Dry, flaky surrounding skin Hair loss (alopecia) in the infective area	This patient presented with ringworm on the arm, or tinea corporis due to Trichophyton mentagrophytes.
Extramammary Paget’s disease	Most common cause is the underlying malignancy such as: Underlying cutaneous adnexal carcinoma (mainly apocrine type) Sometimes arises from periurethral, eccrine, perianal, or Bartholin's glands Internal carcinoma of bladder, rectum, cervix, prostate, or urethra	Paget's cells (large cells with abundant amphophilic or basophilic, finely granular cytoplasm, large centrally-located nucleus with prominent nucleolus) and signet ring cells Arises from keratinocytic stem cells or from apocrine gland ducts	Frequently occurs in areas of abundance of apocrine sweat glands such as: Vulva Perineum Scrotum Perianal skin Penis	Irregular, or ring-shaped, erythematous, or white, eczematous skin plaque “Strawberries and cream” appearance due to scattered areas of erosion and white scale Weeping, crustingerosions Ulceration ‘Underpants-pattern erythema’ in the groin area which spreads peripherally to the areas covered by underwear (due to lymphatic system invasion)	[[File:Extramammary Paget's Disease.png|thumb|200px|none|Extramammary paget's disease [Source: Wikimedia Commons]]