*Contributed equally
Primary urethral carcinoma (PUC) has rarely been reported, notably with variant histology. The present case reports a 68-year-old male patient with a 3-month history of difficulty voiding urine accompanied by a burning sensation in the urinary tract and hematuria. Urethrography and computed tomography (CT) indicated a mass localized in the urethral bulb. A fine needle biopsy revealed the mass to be a malignant tumor of the urethra. Partial penectomy was eventually performed and postoperative histopathological examination confirmed that the lesion was PUC, with mixed characteristics of urothelial and squamous differentiation. The patient was postoperatively followed up and at 9 months, a repeat CT scan revealed local recurrence and metastases. The patient rejected further treatment and eventually succumbed to the disease three months later. The present case report demonstrates an example in which urothelial and squamous differentiation simultaneously exist in the pathological report. The clinical features, diagnosis and treatment status of PUC were also summarized and analyzed to improve the clinical understanding of this unique disease.
Primary urethral carcinoma (PUC) is an aggressive and infrequent carcinoma, accounting for ≤1% of malignant tumors of the genitourinary system (
The presence of tissue variations in the pathological reports is very important due to their prognostic and therapeutic significance (
A 68-year-old man who presented with the major complaint of an extra-urethral mass and difficulty voiding urine was treated at the Affiliated Hospital of Guizhou Medical University (Guiyang, China). A hard mass with poor mobility and an approximate size of 3x2 cm could be palpated in the overhanging part of the penis approximately 1.5 cm from the distal end of the penile bulb. The prostatic findings were normal and no enlarged lymph nodes were found by bilateral inguinal palpation. No abnormalities were found in the remaining laboratory tests except for hematuria, which was indicated by urine analysis.
The patient had undergone several imaging examinations. Urethrography indicated an apparent urethral stricture (
Microscopic findings (
Therefore, the patient was discharged. During the 3-month postoperative follow-up, no apparent abnormality was noted according to the laboratory or imaging examination. However, 9 months later, the patient returned to the hospital due to recurrent dysuria with hematuria and a re-examination of abdominal enhancement CT indicated that the enhancement of the anterior part of the cavernous body was decreased (
PUC is defined by the European Association of Urology as a tumor with its very first lesion located in the urethra (
As an invasive examination, diagnostic urinary cystoscopy and biopsy can initially evaluate urinary tract tumors based on the extent, location, and potential histology of the tumor (
Given the rarity and lack of level I evidence of primary urethral cancer, a limited number of prospective multi-agency studies have determined the optimal treatment for PUC. For several years, partial or radical penectomy for distal tumors and total penectomy with cystoprostatectomy for proximal tumors were the standard treatments for urethral cancer. A retrospective cohort study of 1,544 non-metastatic patients with PUC indicated that the overall 5-year survival rate of patients who received local treatment or radical surgery was considerably higher than that noted in patients who did not undergo surgery at the primary site (
Radiation therapy (RT) or chemotherapy are the two standard treatment options for the treatment of patients with PUC in addition to surgery. In localized PUC, the survival rate and recurrence rate of RT are worse than those of surgery. In addition, the patients experience a higher number of side effects, which limit the application of RT in genital protection therapy (
In recent years, with the deepening of our understanding of tumor immunology, systemic immunotherapy targeting immune checkpoint inhibition has been explored and applied in the field of urothelial cancer (
In general terms, different histological results are closely related to the presence of high-level and high-stage diseases (
Pathological diagnosis is primarily based on morphology and immunohistochemistry, but when there are boundary features and tissue artifacts or morphological overlap, it will hinder the best evaluation of morphology, so the presence of immunohistochemical biomarkers may help differentiate between UCSD and traditional urothelial carcinoma. According to Gaisa
Squamous differentiation has important diagnostic, prognostic, and therapeutic implications. This includes UCSDs or the new entities termed ‘PUCs’. Ignoring this particular subtype may lead to an increased risk of clinical understaging and occult metastatic disease. However, the present case report has inherent limitations, such as the inability to generalize the findings reported, the inability to determine causality, and the risk of overinterpretation. In addition, since the Department of Pathology of our hospital did not report the lymphatic vessel, vein, or perineural invasion of the tumor, unfortunately, the specific mode of tumor invasion could not be elucidated. Despite these drawbacks, in future studies, individualized, risk-based, sex-specific treatment strategies for PUC are anticipated to be developed, based on the following important risk factors: Tumor location, clinical and pathological tumor stage, and histological classification. Furthermore, additional similar cases and potential molecular determinants will be of great significance for subsequent investigations since UCSD in PUC appears to be generally underrecognized and underreported.
In conclusion, the present study recommends that additional caution should be paid in patients with pathological findings suggestive of UCSD in PUC.
Not applicable.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
KT contributed to the concept and design of the case report. KT, ML, and SX participated in the surgery. ML produced the first draft of the article. SX and JH obtained the raw data of the patient, such as laboratory and imaging examinations and preliminary examination results, and participated in the diagnosis and treatment of the patient. YM and KC collected the postoperative pathological results and advised on patient treatment. KT, BC, and WZ critically revised the manuscript with regard to the content. All authors confirm the authenticity of the data and have read and approved the final manuscript.
Not applicable.
Written informed consent was obtained from the daughter of the patient for publication of this case report and of the accompanying images.
The authors declare that they have no competing interests.
Imaging examination and gross specimens of urethral tumors. (A) Retrograde urethrogram demonstrated urethral strictures of the bulbar urethra and the uneven wall of the urethra. (B) A lower abdominal CT examination indicated that the tumor was located in the urinary bulb and its dimensions were approximately 4.0x2.0x2.0 cm. The tumor indicated apparent inhomogeneous enhancement. (C) Partial penectomy of the urethral tumor. (D) The mass following partial penectomy. (E) Re-examination of abdominal enhancement CT demonstrated uneven enhancement of the anterior part of the corpus cavernosum of the penis. (F) Enlarged left inguinal lymph nodes with apparent enhancement. CT, computed tomography.
Histopathological examination of the resected specimen. (A) H&E staining of tumor sections indicated infiltrative growth of cancer nests in the stroma. Certain cells had rich cytoplasm and were slightly eosinophilic with large and deep stained nuclei and paving stone-like changes. The differentiation of the squamous epithelium and the proliferation of the surrounding fibrous tissue was also noted (original magnification, x200). Immunohistochemical staining of the tumor cells revealed positive expression for (B) CK5/6 (original magnification, x40), (C) P40, (original magnification, x100), and nuclear focal and weak positivity for (D) GATA-3 (original magnification, x40). H&E, hematoxylin and eosin; CK5/6, cytokeratin 5/6; GATA-3, GATA-3, GATA binding protein 3.