Prostate Biopsy in Young Patients with Hematospermia Without an Indication for Biopsy Contributed to the Early Diagnosis of Prostate Sarcoma: A Case Report

Background: Prostate sarcoma is a rare group of prostate primary malignant tumors with a poor prognosis, and its early diagnosis is challenging. Here we report a case of early diagnosis of prostate sarcoma and summarize the clinical characteristics of this group of patients. Case presentation: We present a case of a 40-year-old male patient with prostate leiomyosarcoma having hematospermia as the initial symptom. His prostate-specic antigen was 2.97 ng/ml, magnetic resonance imaging showed a prostate nodule with possible bleeding at the lesion margins with Prostate Imaging Reporting and Data System (PI-RADS) category 2. According to the guidelines, prostate biopsy was not recommended, but we learned from our previous experience and still recommended him for prostate biopsy. With his consent, a combined prostate biopsy was performed, and he received an early diagnosis of prostate leiomyosarcoma 19 days after the initial symptom of hematospermia. Reviewing previous cases of prostate sarcoma patients at our medical center, we found that the best time for diagnosis and treatment were generally missed. Conclusions: Combination with magnetic resonance imaging is contributive to the early diagnoses of prostate sarcoma. Therefore, when young patients present with repeated hematospermia, even if they have normal prostate-specic antigen, it is important to be alert to the possibility of prostate sarcoma, and multiparametric magnetic resonance imaging rather than ultrasound is recommended, and if MRI reveals prostate lesions, it is recommended to be biopsied regardless of PI-RADS categories, and a combined biopsy is recommended.


Introduction
Prostate sarcoma is a rare type of prostate primary malignant tumors with a rapid progression and poor prognosis (1).
Early diagnosis and early treatment of prostate sarcoma improve the prognosis of patients, however, early diagnosis is challenging (2). The di culty in early diagnosis is mainly due to the rareness of prostate sarcoma and the fact that it tends to occur in young men, which is very different from prostate cancer. When these young patients show symptoms such as dysuria, frequent urination, urgent urination, painful urination, and hematuria, an ultrasound examination is generally recommended. However, an early-stage prostate sarcoma can be insigni cant on ultrasound and can be misdiagnosed as seminal vesiculitis or prostatitis. Later when the patients' symptoms worsen, they will go back to the hospital for further examination, and by then the best time for treatment is often missed.
Prostate Imaging Reporting and Data System (PI-RADS) is an analysis system for multiparametric magnetic resonance imaging (mpMRI) results of prostate cancer (3). Only 3% of PI-RADS categories 1-2 lesions are diagnosed as clinically signi cant prostate cancer (csPCa) by systematic biopsy(4), and therefore prostate biopsy is not recommended for PI-RADS categories 1-2 according to the guidelines, unless other clinical risk factors are considered (5,6). Instead, in our case report, the patient with PRADS category 2 and normal PSA level was found to have prostate leiomyosarcoma.
We believe that at least MRI should be performed in patients with repeated hematospermia instead of ultrasound even if they had normal PSA level to detect an early-stage prostate sarcoma, and if there are any suspicious ndings, regardless of PI-RADS categories, prostate biopsy should be performed.

Case Presentation
A 40-year-old male presented to our urology department with hematospermia. He had continuous hematospermia after several sexual intercourses for the last one month. The hematospermia symptom was not accompanied by painful ejaculation, painful discomfort in the genitals, hematuria, scrotal enlargement, bleeding from other parts of the body, skin petechiae, hot ashes or night sweats. He had chronic symptoms of frequent urination and urgent urination and he was diagnosed with benign prostatic hyperplasia 8 years ago and did not take treatment. His vital signs were stable. A slightly enlarged prostate with a shallow central sulcus and a tougher texture were revealed in the rectal examination, no nodules were found, no pressure pain and the rest of the physical examination was unremarkable. He underwent a PSA and MRI examination. The results showed that TPSA was 2.97 ng/ml, FPSA was 0.249 ng/ml, F/T was 0.08. A nodule was present on the left peripheral side of the prostate, with possible bleeding at the margins of the lesion; besides, the prostate was mildly enlarged, volume 50*40*43 mm, and PI-RADS assessment category was 2, meaning the presence of clinically signi cant prostate cancer is unlikely ( Fig. 1A-L). According to the guidelines(6), prostate biopsy is not recommended, but we learned from our previous experience and still recommended him for prostate biopsy. With the patient's consent, he underwent a combined biopsy (Fig. 2). Immunohistochemical results showed CK ( Based on the pathological ndings and the MRI results, the diagnosis of prostate leiomyosarcoma could be con rmed. The patient underwent a further PET/CT examination to clarify the tumor's metastasis. The PET/CT whole-body imaging results showed a low-density mass in the left outer zone of the prostate, measuring approximately 3.0*2.7 cm, with PET showing a heterogeneous increase in radioactive uptake and a SUV max value of 6.6, which was consistent with the characteristics of leiomyosarcoma. In addition, the punctate dense shadow was seen in the prostate. The prostate was enlarged with calci cation. No abnormalities were detected in the bladder, bilateral seminal vesicles, or rectum, and no distant metastases were detected (Fig. 1M).
He was subsequently treated with robotic-assisted laparoscopic prostatectomy. After surgery, his condition was stable and he had no adverse reactions. After 7 days of observation, he felt well and was discharged from the hospital. Postoperative pathological ndings were consistent with biopsy results (Fig. 3). Postoperative pathology showed no tumor involvement was found in the prostate basal and apical margins, which indicated that he might have a better prognosis. Three months after surgery, the patient's follow-up MRI results showed no recurrence or metastasis. His medical timeline is present in Fig. 4A.
From 2012 to the present, we have admitted ve patients with prostate sarcoma, three with leiomyosarcoma and two with rhabdomyosarcoma (Table 1). We found that PSA were normal in all ve patients. And their age distribution is wide, ranging from 26 to 80, with a median age of 40. Their duration from initial symptoms to diagnosis differ from 19 days to over 1 year. With the exception of the case we reported, other 4 prostate sarcoma patients all died of distant metastases, with overall survival range from 3 months to 7 months. We summarized their treatment process and found that most prostate sarcoma patients were missed at their rst visits (Fig. 4).
Patient PT001 is the patient described in the text, other 4 are previous patients at our medical center. Abbreviation: PSA, prostate-speci c antigen; US, ultrasound; MRI, magnetic resonance imaging; TRUS, transrectal ultrasound-guided prostate biopsy.

Discussion
Prostate sarcoma is very rare, with an incidence of less than 0.1% of prostate malignancies(1). It has a poor prognosis and relies primarily on surgical treatment. Generally, prostate sarcomas extend beyond the prostate and invade adjacent structures (7). Patients who do not have invasive cut margins, basement membrane invasion, prostate apex involvement, or distant metastases tend to have a better prognosis(8, 9). The tumor of the patient reported above did not break through the basement membrane and we believe that he would have a better prognosis. Therefore, early diagnosis of the disease and prompt surgical treatment will greatly improve the prognosis. Our case of a patient whose diagnosis was con rmed by early biopsy beyond the guidelines provides a precedent for future clinical work. Prostate biopsy is recommended for the early detection of prostate sarcoma in young patients with recurrent haemospermia, even if their PSA is not high and with PI-RADS categories 1-2, and a combined biopsy is recommended for its high diagnostic accuracy compared with targeted biopsy alone or systematic biopsy alone(10).
Referring to all 5 patients with prostate sarcoma at our medical center from 2012 to the present, we found that the duration between their initial symptoms and diagnoses varied, mainly because patients visited the hospital for symptoms such as dysuria, hematuria and hematospermia, they underwent ultrasound but ultrasound did not reveal the possibility of an earlystage prostate sarcoma, so they were considered to have seminal vesiculitis or prostatitis and were treated accordingly. As the tumor progressed, symptoms would worsen, and the patient would come for further examination. However, it was the general situation that the prostate sarcoma has extended beyond prostate or has even formed distant metastasis (7).
Therefore, a detection method combined with MRI is necessary to improve patients' prognoses, and MRI rather than ultrasound is recommended for young patients with repeated hematispermia and normal PSA. Besides, we found that PSA was di cult to have positive ndings, even in patients who have developed invasion and metastasis to adjacent organs (Table 1), which is consistent with the previous ndings (7). Their overall survival was relatively short compared to other reported patients (8, 11), mainly because these patients had metastatic tumor at the time of diagnosis and subsequently had positive surgical margins, which indicated poor prognoses.