Non-human papillomavirus penile squamous cell carcinoma with unusual coral-like polymorphic lesion

Abstract

Penile cancer is a rare malignancy of the male genital system. Approximately 98% of penile cancer corresponds to squamous cell carcinoma (SCC), with further morphological and molecular classification into human papillomavirus (HPV) dependent and non-HPV SCC. Compared to HPV-induced SCC, non-HPV SCC appeared to have a worse prognosis. Here, we present a case of an uncircumcised male with an unusual coral-like polymorphic lesion, and confirmed histopathology of well-differentiated non-HPV penile SCC with rapid growth progression.

INTRODUCTION

Penile cancer is a rare malignancy of the male genital system. Although the prevalence of penile cancer is relatively small and diagnosis is usually easy to make, in cases in which penile-sparing modalities are not an option, the treatment may lead to a more extensive treatment method, such as partial penectomy or total penectomy.[1]

Approximately 98% of penile carcinoma corresponds to squamous cell carcinoma (SCC), which arises from the squamous mucosal tissue involving the anatomical structure of the penile glans, coronal sulcus and inner preputium, with further morphological and molecular classification into human papillomavirus (HPV) dependent and non-HPV SCC.[2] Epidemiological studies revealed that the risk factors are uncircumcised, high number of sexual partners, tobacco and alcohol consumption, and HPV infection. Non-HPV SCC is highly associated with chronic inflammation or premalignant precursor lesions of the penis.[1]

Here, we present a case of an uncircumcised male with an unusual coral-like non-HPV penile SCC with rapid growth progression.

CASE REPORT

A 51-year-old Southeast Asian male without prior history and comorbidities presented with a 3-month history of asymptomatic coral-like penile mass growing at an alarmingly fast rate. According to the patient’s recollection, the lesion first appeared as a singular nodule located on the ventral side of the inner preputium. The nodular lesion begins to increase in size and number, growing outward and circularly, covering the entire prepuce. Initially, the patient did not seek medical help because the lesion was painless, and the patient did not have any urinary symptoms. The patient denied other medical history and past surgery. Prior to the visit, the patient denied ever having preexisting penile skin condition or lesion. The patient reported a monogamous relationship with his spouse and denied promiscuity. The only relevant risk factor that the patient disclosed was 30 years of smoking history. Laboratory analysis was insignificant. The patient tested negative for HIV and other sexually transmitted diseases.

Initial physical examination revealed a multifocal, polymorphic lesion, with a prominent yellowish coral-like mass growing outward from the prepuce and a visible lump-like mass in the mid-distal corpora, as shown in Figure 1. There is a 2 cm large irregular erythematous protruding nodule on the side of the prepuce. The ventral side appeared to have ulceration with suppurative purulence discharge. The prepuce could not be retracted to reveal the glans and the external urethral orifice. On palpation, the lesion was painless and noncompressible, with little mobility. The inguinal lymph node was not palpable. Due to the size of the mass and suspected malignancy, the patient was scheduled for mass resection under epidural anesthesia.

Figure 1.

Coral-like mass covering the glans and external urethral orifice

Circumferential incision and excision of the prepuce were made 2 cm distal to the mass. Intraoperatively, the glans and the external urethral orifice was visible after the prepuce was excised, multiple cauliflower-like mass was seen on the glans, infiltration of the mass can be seen on the corpora cavernosa around the glans neck. Urethrocystoscopy was performed to assess the urethra, and direct visualization was clear. Partial penectomy was performed on the patient, and the resection was sent to pathology for further examination. Figure 2 reveals the surgical process and the resected tumor tissue.

Figure 2.

(a and b) Partial penectomy, the mass can be seen infiltrating the corpora cavernosa (white arrow), (c) Multiple cauliflower-like mass (white arrow), (d) Dissected specimen of the glans and penile mass

Surgical pathology of the prepuce and partially resected penis revealed coralloid, fragile yellowish tumor tissue. Histomorphology revealed non-HPV-related well-differentiated SCC (pT2), as shown in Figure 3. Nests of infiltrative malignant cells with a high nuclear/cytoplasmic ratio can be seen around the subepithelial stroma. The cellular infiltrate was polygonal with pleomorphic and hyperchromatic nuclei. The formation of keratin pearls can be seen. In addition, there is evidence of infiltration of the malignant epithelial cells in the corpus spongiosum and cavernosum. There is no evidence of urethral involvement from the dissected specimens.

Figure 3.

H and E, low and high magnification of the dissected specimen. (a-c) Well-differentiated SCC. Invasive tumor nests extend into the deep dermis layer. The cells are composed of well-differentiated squamous cells that grow in ample sheets with an irregular nesting pattern, little intervening reactive stroma, with chronic inflammatory response, (d and e) Nuclear polymorphism, mild nuclear atypia, retained squamous maturation with gradual keratinization, ample and eosinophilic cytoplasm, mitosis is infrequent with variable amounts of keratin pearls (★). SCC: Squamous cell carcinoma 100x and 400x

Postoperative computed tomography with the contrast of the pelvis indicated inguinal lymph node involvement. The patient’s tumor classification was pT2N1M0. Following the postoperative evaluation, the patient was referred to oncology to be given chemotherapy and monitored according to the European Association of Urology guidelines.[3]

DISCUSSION

SCC is one of the most prevalent primary tumors of the penis.[4] Classification of SCC is divided into two distinct subtypes based on HPV involvement, the majority of which are caused by prior HPV infection.[2] The patient often presents with a painless skin lesion or nodule. Considering the visibility and the presentation of the lesion, in most cases, the diagnosis of penile cancer can be made early and straightforwardly. Non-HPV SCC accounts for only 2% of penile carcinoma, it is not a novel subtype. However, the morphology and clinical presentation of this case report are noteworthy due to the unique shape and the rate of growth of the mass. In this study, we present a non-HPV well-differentiated SCC based on the pathological morphology features of the dissected samples.

Currently, the pathogenesis and carcinogenesis mechanism of non-HPV is not properly understood. It is hypothesized that non-HPV SCC arises from precursor lesions and might be induced by prior inflammatory skin diseases.[5] As with the case of our patient in this report, the histopathology is well-differentiated with keratinizing maturing malignant cells. Compared to HPV-induced SCC, non-HPV SCC appeared to have a worse prognosis.[4] Non-HPV SCC is associated with TP53 mutations, which could be attributed to the chemoresistance and radioresistance due to the permanent inactivation of TP53, patients with non-HPV SCC often have a poorer response to chemotherapy and radiotherapy compared to HPV-induced SCC.[4] Due to the invasive nature of penile cancer treatment, which often requires partial or total penectomy, early diagnosis, and surgical treatment should be made along with an informed discussion with the patient to improve the patient’s survival rate. Yet, despite the uniqueness of non-HPV SCC, the current guideline for the treatment is the same regardless of HPV involvement.[3] Future studies are warranted for a better understanding of the molecular pathogenesis and more efficient and targeted treatment modalities for non-HPV SCC.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.