Penile Intraepithelial Neoplasia Overview

Penile intraepithelial neoplasia (PeIN or PIN) is a histological condition that is characterized by premalignant lesions on the surface of the penis. These lesions are mainly found on the shaft skin and on the prepuce covering the glans. PeIN may be categorized as differentiated and undifferentiated PINs.

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This condition has high mortality and morbidity rates in males around the age of 35. The effect of PeIN is found to be much less in countries like England, where the affected rate is just one in one  hundred thousand males, whereas in developing countries in the African continent, the affected rate is significantly larger.

Classification

Undifferentiated PeIN is categorized as warty, basaloid, and warty-basaloids. The subtypes of penile lesions cannot be distinguished macroscopically, but they produce microscopic characteristics such as parakeratosis, acanthosis, hyperchromatic cells, and enlarged keratinocytes in the basal layer.

• Warty lesions in the penis are a rare neoplasmic condition, characterized by unusual parakeratosis, a sharp surface, and pleomorphic koilocytosis.

• In basaloid PeIN, the epithelial surface of the penis is replaced by monotonous number of uniformly, small, round-shaped basophilic cells.

• Warty-basaloid PeIN is a combination of both types and exhibit the features of both warty and basaloid PeINs.

Causes

There are various factors that cause penile lesions.

• Viral infections due to human papillomavirus (HPV) are a major cause of PeIN.

• The development of HIV infection causes weakening of the immune system and leads to PeIN.

• Balanitis is a condition that causes penile lesions due to poor personal hygiene.

• Phimosis is the inability to backtrack the foreskin over the glans, resulting in penile malignancy.

• Tobacco chewing and cigarette smoking are causative agents of PeIN.

• Exposing the penile surface to ultraviolet rays causes penile tumors.

Signs and symptoms

• HPV penile lesions occur in the form of lobules with an irregular surface that appears on the perineum and perianal areas.

• Genital herpes produces symptoms of itching, scarring, sensation of burning, and appearance of sores on the surface of the penis.

• Lichen sclerosus causes symptoms of severe pain in the penile region, bleeding and itching, and appearance of phimotic prepuce that serves as a causative factor.

• Carcinoma in situ is a condition that has symptoms such as pruritus and pain on the penile surface area.

Other common symptoms include painful urination, discharge from the penis with foul smell, and formation of a crusty or scaly layer on the penile region.

Diagnosis

Diagnosis of penile lesions is a simple procedure with histopathological and physical examinations to detect abnormalities in the penis.

Histopathological examination involving a punch biopsy is done before undergoing a treatment procedure to detect and verify the condition of penile lesions. Diagnosis of HPV infection is done by a combination of reverse hybridization and polymerase chain reaction (PCR) technique on the punch biopsy sample.

Physical examination of the malignant penile is done using imaging techniques such as x-ray, computed tomography, and ultrasound to diagnose the lesions. The diagnosed result is exophytic ulcerative lesions that are associated with painless, fistulized inguinal lymphadenopathy, multiple inguinal lymph nodes, and heterogeneous tissue forming on the penis.

Laboratory diagnosis provides normocytic and normochromic anemic condition, decreased prothrombin time, increased leukocytes, and differentiated squamous cell carcinoma penetrating the penis.

Treatment procedures

Lesions in the penis can be treated by performing topical therapies that include topical chemotherapy and topical immunotherapy, laser treatment using CO2 and Nd:YAG lasers, photodynamic therapy (PDT), cryotherapy, surgical excision, and moh’s micrographic surgery.

In topical treatment, topical chemotherapy is a first-line medication that uses 5-fluorouracil to treat the penis. The treated region heals within 4–8 weeks. The response rate is less than 10%. This process is followed by topical immunotherapy, a second-line medication that employs imiquimod cream to treat the ailment with an about 70% complete response rate.

Laser therapy uses Co2 and Nd:YAG lasers in which Co2 laser has a penetration depth of 22.5 mm and a healing period of 34 weeks. The Nd:YAG laser has a penetration depth of 35 mm with 23-month healing period.

Cryotherapy uses liquid nitrogen and nitrous oxide to treat the penile lesions; in this therapy, there is risk of recurrence compared with other treatment procedures.

Photodynamic therapy employs photosensitizing cream constituting of delta-5-aminolaevulinic acid on the lesions of the penis. It is then exposed to PDT light for recovery. The recovery period is about 35 months.

Surgical excision involves total glans resurfacing (TGR) and partial glans resurfacing (PGR) techniques for treatment of penile lesions. TGR comprises general anesthesia to remove the diseased region of the penis without any surgical margins. PGR involves a similar procedure, but has positive surgical margins.

Mohs micrographic surgery isolates complete penile lesion into thin sections. It is a time-consuming and difficult process, so it is rarely employed.