Erythroplasia of Queyrat

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]

Synonyms and keywords: EQ

Overview

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.

Historical Perspective

  • 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.

Classification

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.

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: I, II, III, and IV.

Jackson's Staging System for Squamous Cell Carcinoma of Penis

[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

Histopathological Features

  • 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)

Pathophysiology

The pathogenesis of Erythroplasia of Queyrat is characterized by squamous cell carcinoma 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.

Causes

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

Differentiating Erythroplasia of Queyrat from Other Diseases

Erythroplasia of Queyrat must be differentiated from other diseases that cause Squamous cell carcinoma of penis. Differentials include:

  • Bowen's Disease[6]
  • Bowenoid Papulosis
  • Verrucous carcinoma: A verrucous carcinoma growing on the penis is also known as Buschke-Lowenstein tumor. This is an uncommon form of squamous cell cancer that can start in the skin in many areas. This cancer looks a lot like a large genital wart. Verrucous carcinomas tend to grow slowly but can sometimes get very large. They can grow deep into nearby tissue, but they rarely spread to other parts of the body.

Epidemiology and Demographics

  • 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, in which it constitutes a small proportion of the total cancers.[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.
  • Circumcision later in life does not seem to confer protection.

Age

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

Gender

  • Males are affected with Erythroplasia of Queyrat.

Risk Factors

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:

Screening

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

  • The physician will ask about patient medical history and the details of their symptoms, such as when they started and if they've changed. Possible risk factors of the patient will also be discussed.
  • 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.

Natural History, Complications, and Prognosis

If left untreated, patients with Erythroplasia of Queyrat may progress to develop invasive squamous cell carcinoma of the penis.[11] Because penile cancer is not common, it's hard to find accurate survival rates based on the TNM stage of the cancer. The numbers below come from the National Cancer Institute’s Surveillance Epidemiology & End Results (SEER) Program database, looking at more than 1,000 men diagnosed with penile cancer between 1988 and 2001.

  • For cancers that are still confined to the penis (stage I and II cancers), the 5-year relative survival rate is around 85%.
  • If the cancer has spread to nearby tissues or lymph nodes (stage III and some stage IV cancers), the 5-year relative survival rate is around 59%.
  • If the cancer has spread to distant parts of the body, the 5-year relative survival rate is about 11%.

Treatment in the early stages of penile cancer is critical for good long-term results and predominantly preserves quality of life by preserving normal sexual function.

Diagnosis

Diagnostic Study of Choice

  • 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.

Symptoms

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

History and Symptoms

  • 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 skin changes in the penile skin including color and thickness changes, chronic irritation , and lesion growth. Common symptoms of Erythroplasia of Queyrat include persistent, foul smelling discharge under foreskin, smegma, dysuria, weak urine stream, loss of sensation in glans, and inability to fully pull back foreskin over glans.

Physical Examination

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.

Laboratory Findings

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

Electrocardiogram

There are no ECG findings associated with Erythroplasia of Queyrat.

X-ray

There are no x-ray findings associated with Erythroplasia of Queyrat. However, if it has been proven cancer has spread to the lungs a chest x-ray might be done.

Echocardiography or Ultrasound

There are no ultrasound findings associated with Erythroplasia of Queyrat. However, an ultrasound may be helpful in the diagnosis of complications and to assess how deep the cancer has spread in the penis.

CT scan

There are no CT scan findings associated with Erythroplasia of Queyrat. However, a CT scan may be helpful in assessing the size of the precancerous lesion as well as to see if the cancer has spread to lymph nodes or other parts of the body.

CT-guided needle biopsy

CT scans can be used to guide a biopsy needle into an enlarged lymph node or other area that might be cancer spread.

MRI

There are no MRI findings associated with Erythroplasia of Queyrat. However, a MRI may be helpful in the diagnosis of complications of this precancerous lesion as well size and spread of the cancer if late initial diagnosis.

Other Imaging Findings

There are no other imaging findings associated with Erythroplasia of Queyrat.

Other Diagnostic Studies

There are no other diagnostic studies associated with Erythroplasia of Queyrat.

Treatment

Medical Therapy

The mainstay of therapy for Erythroplasia of Queyrat is Imiquimod or 5-fluorouracil for several weeks to months. A therapeutic regimen of 5% 5-fluorouracil cream applied to lesion(s) twice daily for four to five weeks has produced a high cure rate and maintained penile integrity and function.[13] [14]

There are several non-invasive treatment options for Erythroplasia of Queyrat. These include:

  • Photodynamic therapy
  • Cryosurgery
  • Applying various kinds of topical agents

Pharmacologic Medical Therapy is recommended among all patients who develop Erythroplasia of Queyrat.

Surgery

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- uses an intense, narrow beam of light (called a laser beam) to destroy cancer cells.
  • Cryosurgery uses extreme cold to freeze and destroy tissue.

Primary Prevention

There are no established measures for the primary prevention of Erythroplasia of Queyrat. However, researchers continue to look into various factors that may prevent this stage 0 cancer since there are no available vaccines against Erythroplasia of Queyrat. Effective measures for primary prevention include:

Secondary Prevention

There are no established measures for the secondary prevention of Erythroplasia of Queyrat.[11]

References

  1. . 2009. doi:10.1016/B978-1-4160-3966-2.X0001-X. Missing or empty |title= (help)
  2. 2.0 2.1 Hakenberg, Oliver W.; Compérat, Eva M.; Minhas, Suks; Necchi, Andrea; Protzel, Chris; Watkin, Nick (2015). "EAU Guidelines on Penile Cancer: 2014 Update". European Urology. 67 (1): 142–150. doi:10.1016/j.eururo.2014.10.017. ISSN 0302-2838.
  3. Lynch DF Jr. Cancer of the Penis. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003. Available from: https://www.ncbi.nlm.nih.gov/books/NBK13419/
  4. Marks, James G; Miller, Jeffery (2006). Lookingbill and Marks' Principles of Dermatology (4th ed.). Elsevier Inc. Page 63. ISBN 1-4160-3185-5.
  5. Clark PE, Spiess PE, Agarwal N, Biagioli MC, Eisenberger MA, Greenberg RE; et al. (2013). "Penile cancer: Clinical Practice Guidelines in Oncology". J Natl Compr Canc Netw. 11 (5): 594–615. PMC 4042432. PMID 23667209.
  6. Brady, Kimberly L.; Mercurio, Mary Gail; Brown, Marc D. (2013). "Malignant Tumors of the Penis". Dermatologic Surgery. 39 (4): 527–547. doi:10.1111/dsu.12029. ISSN 1076-0512.
  7. Bleeker MC, Heideman DA, Snijders PJ, Horenblas S, Dillner J, Meijer CJ (2009). "Penile cancer: epidemiology, pathogenesis and prevention". World J Urol. 27 (2): 141–50. doi:10.1007/s00345-008-0302-z. PMID 18607597.
  8. Bleeker, M. C. G.; Heideman, D. A. M.; Snijders, P. J. F.; Horenblas, S.; Dillner, J.; Meijer, C. J. L. M. (2008). "Penile cancer: epidemiology, pathogenesis and prevention". World Journal of Urology. 27 (2): 141–150. doi:10.1007/s00345-008-0302-z. ISSN 0724-4983.
  9. Douglawi, Antoin; Masterson, Timothy A. (2017). "Updates on the epidemiology and risk factors for penile cancer". Translational Andrology and Urology. 6 (5): 785–790. doi:10.21037/tau.2017.05.19. ISSN 2223-4683.
  10. Salami, Simpa S.; Montgomery, Jeffrey S. (2017). "Surveillance strategies in the management of penile cancer". Translational Andrology and Urology. 6 (5): 868–873. doi:10.21037/tau.2017.06.04. ISSN 2223-4683.
  11. 11.0 11.1 11.2 Schlenker, Boris; Schneede, Peter (2019). "The Role of Human Papilloma Virus in Penile Cancer Prevention and New Therapeutic Agents". European Urology Focus. 5 (1): 42–45. doi:10.1016/j.euf.2018.09.010. ISSN 2405-4569.
  12. Damjanov, Ivan (2009). "The Male Genital System": 329–338. doi:10.1016/B978-0-323-05594-9.00016-7.
  13. Choi, Jee Woong; Choi, Mira; Cho, Kwang Hyun (2009). "A Case of Erythroplasia of Queyrat Treated with Imiquimod 5% Cream and Excision". Annals of Dermatology. 21 (4): 419. doi:10.5021/ad.2009.21.4.419. ISSN 1013-9087.
  14. Antônio, João Roberto; Antônio, Carlos Roberto; Trídico, Lívia Arroyo; Alves, Fernanda Tomé; Rollemberg, Ivan (2016). "Erythroplasia of Queyrat treated with topical 5-fluorouracil". Anais Brasileiros de Dermatologia. 91 (5 suppl 1): 42–44. doi:10.1590/abd1806-4841.20164595. ISSN 0365-0596.