Erythroplasia of Queyrat

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Swathi Venkatesan, M.B.B.S.[2]

Synonyms and keywords: EQ

Erythroplasia of Queyrat is a penile squamous cell carcinoma in situ named after Louis Queyrat, a French dermatologist who was head of the dermatology service of l’Hôpital Ricord, a venereal hospital in Paris, now Hôpital Cochin. The pathogenesis of erythroplasia of Queyrat is characterized as a precancerous lesion of squamous cell carcinoma in situ of the glans penis and inner prepuce or foreskin. Erythroplasia of Queyrat is most commonly observed among white male patients aged 60 years old and older with Human papilloma virus (HPV) infection or chronic irritation and lack of hygiene of pubic area. The most common risk factor in the development of erythroplasia of Queyrat is an uncircumcised penis. The mainstay of therapy for erythroplasia of Queyrat is imiquimod or 5-fluorouracil for several weeks to months.

• Erythroplasia of Queyrat was first discovered and named after Louis Queyrat.^[1]
• Louis Queyrat was French dermatologist who was head of the dermatology service of l’Hôpital Ricord, a venereal hospital in Paris, now Hôpital Cochin.
• Tarnovsky originally described erythroplasia of Queyrat in 1891, but it was Queyrat who originated the term erythroplasia in 1911.

• Erythroplasia of Queyrat is classified as a precancerous lesion.
• The earliest stage of squamous cell cancer of the penis known as Carcinoma in situ (CIS).
• This is also known as stage 0 of penile cancer.
• In this stage, the cancer cells are found only in the top layers of skin; they have not yet grown into the deeper tissues.^[2]
• Depending on the location of the CIS on penis, doctors may use other names for the disease.
  • CIS of the glans or prepuce is called erythroplasia of Queyrat, presents as erythroplakia.
  • CIS on the shaft of the penis (or other parts of the genitals) is called Bowen disease, presents as leukoplakia.
• About 95% of penile cancers start in flat skin cells called squamous cells.
• Squamous cell carcinoma can start anywhere on the penis.
• Most of these cancers start on the prepuce or foreskin (in men who have not been circumcised) or on the glans.
• These tumors tend to grow slowly. If they’re found at an early stage, they can usually be cured.

• Squamous cell carcinoma of penis may be classified according to Jackson’s Staging System into number subtypes/groups:^[3]

Stage	Description
I	Confined to glans of prepuce
II	Invasion into shaft or corpora
III	Operable inguinal lymph node metastasis
IV	Tumor invades adjacent structures; inoperable inguinal lymph node metastasis

• The pathogenesis of erythroplasia of Queyrat is characterized by squamous cell carcinoma (SCC) in situ of the glans penis:^[4]
  • It is a premalignant dermatosis that usually occurs on the glans penis and appears as a well-marginated erythematous velvety patch or plaque.
  • Analogous to Bowen’s disease, infiltration, nodularity or ulceration often suggest the possibility of progression to an invasive squamous cell carcinoma.
  • Transformation of erythroplasia of Queyrat into an invasive SCC is more common than in Bowen’s disease, with an incidence varying from 10% to 33%. This difference could be related to the mucosal location of the disease.
  • When penile submucosa is invaded, the rate of involvement of regional lymph nodes is about 20%.
  • Clinically, the presence of ulceration and/or papillary lesions usually corresponds to progression into an invasive carcinoma.

• Low-grade (I-II)^[2]
  • Well-differentiated lesions show a thickened hyperkeratotic, and papillomatous epidermis
  • Downward fingerlike projection of atypical squamous cells that often appear as concentrically arranged nests of cells surrounding keratin accumulations (keratin pearls).
• High-grade (III-IV)
  • More poorly differentiated squamous cell carcinoma
  • Shows little or no keratinization
  • Increased nuclear pleomorphism
  • Hyperchromatic
  • Deeper invasion; may have areas of necrosis or superinfection

Besides old age and lack of circumcision, erythroplasia of Queyrat has been linked to various factors including:

• Chronic irritation from retained secretions under the foreskin^[5]
• Poor hygiene
• Smegma
• Genital herpes simplex
• Heat
• Friction
• Trauma
• Human papilloma virus (HPV) infection, types 16, 18, 31, 33.

• Erythroplasia of Queyrat must be differentiated from other diseases that cause squamous cell carcinoma of penis:
  • Bowen’s Disease^[6]
  • Bowenoid Papulosis
  • Verrucous carcinoma

• Israel and the United States as well as other industrialized countries, where infant circumcision is common, the incidence of penile squamous cell carcinoma is less than 1 per 100,000 males.^[7]
• Squamous cell cancer accounts for more than 95% of cases of penile cancer. This represents a significant public health problem in several parts of the world where early circumcision and good genital hygiene are less commonly practiced.

• Erythroplasia of Queyrat is more commonly observed among patients aged 60 years old.

• Males are affected with erythroplasia of Queyrat.

Most common risk factor in the development of erythroplasia of Queyrat is uncircumcised penis. Other common risk factors in the development of erythroplasia of Queyrat include:^{[8] [9]}

• Smoking
• Obesity
• Low socio-economic status
• Multiple sex partners
• Immunosuppression
• Ultraviolet (UV) light exposure
• Human papilloma virus (HPV)
• Phimosis
• Zoon balantis
• Underlying dermatoses (lichen planus)
• Chronic inflammation, irritation or infection

There is insufficient evidence to recommend routine screening for erythroplasia of Queyrat.^[10]

• If left untreated, patients with erythroplasia of Queyrat may progress to develop invasive squamous cell carcinoma of the penis.^[11]

• There are no widely recommended screening tests for penile cancer, and many penile cancers can be found early, when they’re small and before they have spread to other parts of the body.^[12]
• The diagnosis of erythroplasia of Queyrat is confirmed with histological examination.
• Delays in the diagnosis and treatment of erythroplasia of Queyrat are common because of two main factors.
  • Early penile SCC often has a varying clinical presentation, mimicking benign disorders.
  • Patients often tend to disregard minimal genital lesions for a long time before seeking medical attention.

Delay in diagnosis of more than 1 year has been observed in 15% to 20% of patients, the reasons usually being embarrassment, guilt, fear, personal neglect, or ignorance.

• The hallmark of erythroplasia of Queyrat is a red, velvety appearing rash beneath the penile foreskin.“Precancerous conditions of the penis – Canadian Cancer Society”.
• The lesions are usually solitary and occasionally erode or ulcerate, but pain is uncommon.
• A positive history of lack of circumcision and lesion growth are suggestive of erythroplasia of Queyrat.
• The most common symptoms of this precancerous condition include:

Penile Skin Changes

• Itching and burning under foreskin
• Thickening of skin
• Skin discoloration
• Lumps
• Ulcers
• Rash; velvety red under foreskin
• Bleeding under foreskin
• Foul smelling discharge under foreskin

Genitourinary Changes

• Dysuria
• Weak urine stream
• Loss of sensation in glans
• Inability to fully pull back foreskin over glans

• The physician will then perform a physical examination of the genital area for possible signs of penile cancer or other health problems.
• Penile lesions (sores) usually affect the skin on the penis.
• This is followed by examination and palpation of the lymph nodes in patient’s groin to see if they are swollen.
• If symptoms and/or the exam suggest you might have penile cancer, other tests will be needed. These might include a biopsy and imaging tests.
• Patients with erythroplasia of Queyrat usually appear red, velvety appearing rash beneath the penile foreskin.
• Physical examination of patients with erythroplasia of Queyrat is usually remarkable for penile skin changes including red, ulcerating, bleeding, and indurated lesion on the glans or red vegetating mass on the glans.

There are no diagnostic laboratory findings associated with erythroplasia of Queyrat.

• The mainstay of therapy for erythroplasia of Queyrat is Imiquimod or 5-fluorouracil for several weeks to months.^[13]
• A therapeutic regimen of 5% 5-fluorouracil (5-FU) cream applied to lesion(s) twice daily for four to five weeks has produced a high cure rate and maintained penile integrity and function.^[14]
• There are several non-invasive treatment options for erythroplasia of Queyrat, including:
  • Photodynamic therapy
  • Cryosurgery
  • Topical agents
• Pharmacologic medical therapy is recommended among all patients who develop erythroplasia of Queyrat.

Surgery is the mainstay treatment of choice for erythroplasia of Queyrat, and is often the only treatment needed for early stage penile cancers. Although, authors have used 5% 5-FU cream with some success.

• Circumcision– recommended when the lesion is limited to preputial skin.
• Mohs microscopic surgery– for patients with aggressive forms of erythroplasia of Queyrat this form of surgical excision is effective.
• Wide local excision– removes the tumor along with a margin of normal tissue around it.
• Laser surgery– an intense, narrow beam of light (called a laser beam) to destroy cancer cells.
• Cryosurgery– extreme cold to freeze and destroy tissue.

There are no established measures for the prevention of erythroplasia of Queyrat.