Benign Prostatic Hyperplasia in a 13-Year-Old Boy

to help understand the pathogenesis of childhood BPH.


Introduction
Benign prostatic hyperplasia (BPH) is a recognized pathology in aging males. It is extremely uncommon in men below 50 years of age. Rare reports have come out in the pediatric population. The literature review reveals about nine reported cases ( Table 1). The rarity of the cases poses a significant challenge in understanding the pathogenesis and treatment in the pediatric population. Our patient was a 13-year-old male who had intermittent gross hematuria and recurrent acute urine retention for 2 years and was finally treated for BPH through open suprapubic prostatectomy.

Case presentation
A 13-year-old patient presented with a 2-year history of intermittent hematuria and recurrent acute urine retention. He was initially evaluated in our facility in December 2018 and discussed in a multidisciplinary meeting. He had no history of urethral instrumentation or pelvic or perineal trauma. He did not have any neurological abnormality, constipation, or kidney stones. There was no prior treatment with hormonal therapy, nor was there a history of prostate gland disease in his family. His antenatal period was normal, with no history of his mother using human chorionic gonadotropin-like hormone supplements. At 11 years, he underwent scrotal orchidopexy for the right undescended testis. He had bilaterally palpable scrotal testes with a well-developed circumcised penis. There were no palpable nodules in the prostate. The prostate-specific antigen (PSA) measurements were all below 0.3ng/mL. The contrast-enhanced computed tomography (CECT) scan performed at the initial presentation demonstrated a prostatic mass of 62 g with other abdominal viscera normal ( Figure 1, A and B). A multidisciplinary meeting decided to offer him transurethral resection of the prostate (TURP) and tumor biopsy. However, a pediatric resectoscope was lacking. Eleven months later, the parents sought treatment from a different facility. The patient was diagnosed with a bladder mass followed by an unsuccessful attempt at open excision of the tumor. The surgery was abandoned after realizing that the tumor was not a urinary bladder tumor ( Figure 2A). However, the patient underwent incisional biopsies ( Figure 2B).

BENIGN PROSTATIC HYPERPLASIA IN A BOY
He was sent back to our facility for further assessment and treatment. Magnetic resonance imaging (MRI) showed an enlarged solid prostatic mass (189 g) with multiple cystic locules, an intact capsule, and a concentric regular bladder wall thickening (Figure 3). His follow-up became irregular with the emergence of the COVID-19 pandemic and the subsequent travel restrictions.
He was eventually admitted through the emergency department to our facility 1 year later, as an emergency with sepsis. A repeat MRI showed an interval increase in the size of prostatic mass to 291 g and the development of a pelvic abscess (Figure 4)  There was no lymph node enlargement or any pelvic or abdominal metastases on imaging. The abscess underwent drainage percutaneously, and he received culture-directed antibiotics. The patient underwent fresh transrectal prostatic biopsies, with a reevaluation of the initial ones. A repeat multidisciplinary tumor board discussion opted for open suprapubic prostatectomy. Intraoperatively, the enucleated prostatic tissue mass was 258 g ( Figure 5). The histological examination of the specimen from open suprapubic prostatectomy revealed a benign prostatic enlargement ( Figure 6). Post-operatively, the patient developed a delay in urinary bladder healing, which was managed OLUOCH ET AL. conservatively through a long stay percutaneous drain and an indwelling urethral catheter. He was discharged from the hospital on the 28th day post-operatively, fully ambulant, and without a urethral catheter or percutaneous drain. His follow-up at our clinic has been uneventful. At 1-year post-operative, he has no lower urinary tract symptoms (LUTS), gained significant weight, and resumed schooling. His total PSA level is 0.201 ng/mL, and total testosterone is 28.47mmol/L. We intend to offer him long-term followup at our urology clinic to monitor complications such as urethral stricture, erectile dysfunction, and retrograde ejaculation and to document his progress and adulthood.

Discussion
BPH is a histologically confirmed noncancerous growth of prostatic tissue. Population-based studies show that it develops after the fourth decade of life, with an agedependent prevalence reaching up to 60% in older men over 50 years (1,2). Pediatric prostatic tumors are sporadic, with only a few cases of rhabdomyosarcoma and BPH reported in the literature (3,4). The pathogenesis of BPH is wide-ranging. Some postulated causes in adults include testosterone, dihydrotestosterone (DHT), increased prostatic stem cells with aging, and prostatic stromal-epithelial interaction (5,6). The testes produce testosterone which is converted into DHT by 5-alpha-reductase type 2 within the prostate stromal cells. DHT accounts for about 90% of prostatic androgens and has autocrine, paracrine, and endocrine effects on prostatic tissue and adjacent cells, hence influencing cellular proliferation and cell death. Growth factors, such as FGF, EGF, TGFbeta, and so on, also impact the growth of the prostatic cells (7). BPH eventually develops due to the loss of control of cell proliferation and cell apoptosis, causing an imbalance in favor of cell proliferation (5). There is a scarcity of data describing the development of BPH in the pediatric age group. Two cases of BPH in childhood had an etiological link. In one case, there was gonadotropin supplementation for cryptorchidism. In the other, a human chorionic gonadotropin-containing drug was used during pregnancy. In the other cases, no risk factors were established (4,8). Our patient did not have any endocrinologic abnormality, had no history of hormonal drug use, or any other potential contributor. Childhood cases like ours without any associated etiology suggest that other etiologic causes are involved. Thus, more information is required. BPH leads to a progressive increase in urethral resistance. The presentation is with LUTS, which encompass storage, voiding, and/or post-micturition symptoms. The urinary bladder responds by compensatory hypertrophy and increased deposition of interstitial collagen, resulting in increased urinary bladder weight. Initially, the enormous bladder bulk is adequate for maintaining good detrusor muscle contractility and voiding, but with persistent obstruction, the bladder decompensates with consequent incomplete bladder emptying and development of complications. The complications include bladder stones, urinary tract infections, urinary retention, and renal insufficiency (9). Our patient had recurrent acute urinary retentions with intermittent hematuria. A palpable mass on digital rectal BENIGN PROSTATIC HYPERPLASIA IN A BOY examination should trigger a clinician to consider a prostatic rhabdomyosarcoma besides a rarer BPH. Imaging evaluation includes ultrasonography, CECT scanning, and MRI (8). Rhabdomyosarcoma is an aggressive tumor leading to early metastasis. Our patient had neither metastases nor lymph node involvement. The initial histopathology reported a spindle cell tumor likely to be a prostatic leiomyosarcoma. As the patient lacked any features of a malignancy, a repeat transrectal biopsy was performed. A team of pathologists reevaluated the specimens and confirmed BPH. Suprapubic open simple prostatectomy was performed. Pre-operative histological diagnosis of BPH precluded the patient from undergoing a more aggressive radical prostatectomy. Treatment of BPH in adults is well established, with international guidelines. The adult guidelines recommend surgery in case of severe LUTS, high pressure chronic urinary retention, persistent gross hematuria, and recurrent urinary tract infections. Without those mentioned above, medical therapy with 5-alpha reductase inhibitors, alpha-blockers, antimuscarinic, and/or phosphodiesterase type 5 inhibitors are used (10). There is no study on the use of these drugs in pediatrics. Simple open prostatectomy is a preferred treatment for a prostate gland of more than 80 g. The scarcity of pediatric cases causes a challenge in developing consensus on the management. The experiences gained from treating adults are used to guide pediatric treatment options. In the published literature, open prostatectomy was performed in most BPH cases in the pediatric age group. TURP was performedon a 10year-old boy with a prostate of 33 g. The author, however, dissuaded urologists from performing TURP in pediatric patients due to quick regrowth (11). Longer post-operative follow-up is required to monitor surgery complications such as urethral stricture, retrograde ejaculation, and erectile dysfunction and to document post-childhood life and progress. Recommended follow-up involves taking history using validated questionnaires such as International Prostate Symptom Score, targeted physical examination, for example, digital rectal examination, PSA level, post-void residual volume, and free uroflowmetry as per the adult practice (12).

Conclusion
BPH is an infrequent disease entity in childhood. Urologists should, however, always be aware of its possibility while evaluating boys with acute urinary retention and prostatic masses. Radiological and histological evaluation is essential in patients who present with LUTS and a suspicious prostate on rectal examination. Optimal urosurgical management in pediatric patients is currently unknown. The practicing urologists may have to borrow from adult management guidelines.

Ethical consideration
Informed consent for publication was obtained from both the patient and the father. This review also underwent ethical approval from the Institutional Review Board with a review, Ref: KNH-ERC/01/PUB/2.

Author contributions
All other authors contributed equally in the conceptualization and writing of the first draft to reviewing and editing the original draft.