Spindle cell embryonal rhabdomyosarcoma of the prostate in an adult patient: a case report and review of the literature

Abstract

Rhabdomyosarcoma of the prostate is a rare mesenchymal tumor that originates from undifferentiated mesenchymal cells. Spindle cell rhabdomyosarcoma is a variant of embryonal rhabdomyosarcoma. The vast majority of these two pathological types occur in children, with only a few adult cases reported to date, and both are associated with poor clinical outcomes. We herein report a case involving a man in his early 40s with spindle cell embryonal rhabdomyosarcoma of the prostate. His chief complaint was difficult urination. The diagnosis was confirmed by puncture biopsy of the prostate, and pelvic lymph node metastasis was already present at the time of diagnosis. The patient underwent three courses of chemotherapy. However, his response to the treatment was very poor, and he died of the disease 4 months after diagnosis.

Introduction

Embryonal rhabdomyosarcoma (ERMS) is the predominant subtype of RMS. It is rare in adults and has a worse prognosis in adults than in children. ¹ Spindle cell RMS (SpRMS) accounts for only 5% to 10% of all cases of RMS. ² Although SpRMS was historically considered a subtype of ERMS, it was defined as a stand-alone entity in the 2013 World Health Organization classification. ³ Later, in the 2020 World Health Organization classification, SpRMS was further divided into three subtypes: congenital, myoblast determination protein 1 (MyoD1) mutant, and intraosseous. ⁴ SpRMS that lacks these molecular alterations is classified as spindle cell ERMS.^5–7 Childhood SpRMS most commonly occurs in paratesticular sites and has a better prognosis than several other subtypes. ⁸ Adult SpRMS was originally reported by Rubin et al. ⁹ Unlike SpRMS in children, SpRMS in adults most commonly occurs in the head and neck; additionally, it has a significantly poorer prognosis than in children, with recurrence and metastasis rates as high as 50%.^8,10 The prostate is considered an unfavorable site for RMS. ¹¹ Prostate ERMS accounts for less than 1% of all prostate malignancies. ¹ Prostate SpRMS has been reported in only a small number of adults. Given the rarity and aggressiveness of this pathologic type, early diagnosis and intervention are crucial for prolonging patient survival.

Case report

A man in his early 40s presented to our hospital with a 2-month history of dysuria and no other relevant medical history. Pre-admission prostate magnetic resonance imaging revealed a mass in the prostate, and its features indicated a high likelihood of sarcoma. After admission, the patient’s prostate-specific antigen concentration was 1.39 ng/mL. Digital rectal examination revealed that the prostate was unevenly enlarged, had a firm texture, and contained palpable nodules on the surface. Pelvic magnetic resonance imaging showed a huge irregular tumor in the prostate measuring approximately 10.5 × 12.4 × 12.5 cm, with clear borders and uneven signals. The tumor showed low signal intensity on T1-weighted imaging and equal/high signal intensity on T2-weighted imaging. Areas of low signal intensity were seen at the edge of the lesion, and nonenhanced necrotic foci were present within these areas. Adjacent tissues such as the bilateral seminal vesicles, bladder, rectum, and bilateral obturator muscles were invaded, and multiple lymph node metastases were present in the left pelvic region (Figure 1). The patient underwent positron emission tomography/computed tomography, but no signs of distant metastasis or bone metastasis were detected (Figure 2). We then performed an ultrasound-guided transperineal prostate biopsy. Microscopic examination showed that the tumor was composed of small, round to spindle-shaped tumor cells with moderate eosinophilic cytoplasm and elongated, deeply stained elliptical to spindle-shaped nuclei. Some of the nuclei contained distinct nucleoli and clearly exhibited nuclear abnormalities characterized by moderate nuclear pleomorphism. Scattered rhabdomyoblasts with eccentric nuclei and areas of necrosis indicating non-viable tumor cells were also present (Figure 3). Immunohistochemistry showed negativity for epithelial membrane antigen, cytokeratin, S-100 protein, and calcium-binding protein (caldesmon) and positivity for vimentin and desmin. Myogenin, MyoD1, anti-smooth muscle antibody, and CD34 showed focal positive expression. The Ki-67 positivity index was >70% (Figure 3). The patient was finally diagnosed with prostate spindle cell ERMS, stage T3N1M0. Because radical surgery was not possible, the patient underwent chemotherapy approximately 2 weeks later, receiving iso-cyclophosphamide for injection +etoposide for injection (IE regimen). The day after the end of chemotherapy, he was found to have low-level colonic obstruction. Under enteroscopy, the rectum was seen to be externally compressed and narrowed approximately 3 to 15 cm from the anus. He then underwent endoscopic intestinal stenting to relieve the obstruction. After the stenting failed, he underwent transanal placement of a decompression tube. Considering that the tumor had severely compressed the rectum and conservative treatment was ineffective, colostomy was performed. Intraoperative examination of the abdominal cavity revealed adhesions of the omentum to the transverse colon, the omentum to the abdominal wall, and the omentum to the small intestine. In the upper rectum, the tumor was compressing the bowel wall and the proximal bowel was dilated. After discharge, the patient underwent two additional courses of chemotherapy at a local hospital, but the outcome was unsatisfactory and he died 4 months after diagnosis.

Figure 1.

Pelvic magnetic resonance imaging showed a large irregular soft tissue mass in the prostate gland. The mass exhibited (a) low signal intensity in T1-weighted imaging and (b) equal/high signal intensity in T2-weighted imaging.

Figure 2.

Positron emission tomography/computed tomography showed (a) a large soft tissue mass in the pelvis, with inhomogeneous density and significantly increased radioactivity uptake, and (b) enlarged lymph node shadows in the left pelvic wall, also with increased radiation uptake. No metastases to other sites were found.

Figure 3.

Small, round to spindle-shaped tumor cells were arranged in fascicles to form bands of cells, and scattered rhabdomyoblasts were seen. The cytoplasm was abundant and eosinophilic. The nuclei were long, darkly stained, and eccentrically arranged and had moderate pleomorphism. (a) Hematoxylin and eosin staining, ×100 and (b, c) Hematoxylin and eosin staining, ×200.

Written informed consent was obtained from the patient’s family for publication of this case report. Before death, the patient was reassured that all of his information would be deidentified. Because this is a case report that does not involve animal or human studies, approval by an ethics committee or institutional review board was not required. The reporting of this case complies with the CARE guidelines. ¹²

Discussion

Spindle cell ERMS of the prostate is rare. The most common sites of this tumor are the extremities, head and neck, paratesticular region, and abdomen. ⁶ Histologic diagnosis of spindle cell ERMS is usually based on the presence of spindle-shaped tumor cells arranged in fascicles, with moderately eosinophilic cytoplasm, long and dark-stained nuclei, many mitotic divisions, and some visible distinct nucleoli with moderate nuclear pleomorphism. Scattered large rhabdomyoblasts with eccentric nuclei are also seen. These findings may be accompanied by areas of tumor cell necrosis.^2,7,9 Immunohistochemically, ERMS typically expresses skeletal muscle markers such as desmin, myogenin, MyoD1, and myoglobin.^7,13,14 We recommend early prostate puncture biopsy in suspicious cases to avoid delay in diagnosis and treatment. In our case, the diagnosis of RMS was confirmed by immunohistochemistry.

Spindle cell ERMS usually has nonspecific symptoms and grows rapidly. It can invade adjacent tissues in a short time. This tumor is usually characterized by a normal serum prostate-specific antigen concentration and symptoms of lower urinary tract obstruction such as dysuria, frequency, and urgency.^7,15 When the rectum is compressed, defecation difficulties or even intestinal obstruction symptoms may develop.^15–17 As a result, the disease usually diagnosed at an advanced stage. Approximately 25% of patients present with distant metastases at the time of diagnosis. ¹⁵ The lung, liver, and bone are the main sites of metastasis.^15,16 An age of ≥10 years, nodal involvement, tumors in unfavorable sites, and large tumors (>5 cm) are risk factors for a poor prognosis. ¹¹ Our patient had all of these risk factors; thus, his poor prognosis was not unexpected.

The MyoD1 pathogenic variant (mainly referred to as the MyoD1 p.L122R mutation) is a characteristic pathogenic variant in SpRMS, but it also occasionally occurs in ERMS. This variant is associated with a poor prognosis.^10,18–20 The largest cohort study of patients with MyoD1 pathogenic variant RMS to date included 30 patients, more than half of whom developed local recurrence and distant metastases after treatment. The results suggest that the MyoD1 pathogenic variant is a manifestation of a highly aggressive tumor regardless of age and phenotype at the time of diagnosis. The mortality rate remains high despite treatment with multiple modalities. However, the clinical significance remains uncertain because tumors without this pathogenic variant exhibit the same aggressiveness and poor prognosis.^18–21 Therefore, detecting the MyoD1 pathogenic variant in SpRMS not only helps to achieve the diagnosis but also has a certain predictive effect on the prognosis. Our patient did not undergo genetic testing, and whether he had the MyoD1 pathogenic variant is unclear. Therefore, we classified his tumor as spindle cell ERMS.

Compared with other types of sarcomas, RMS has a higher propensity for regional lymph node metastasis, which occurs in up to 36% of cases.^22,23 Therefore, the presence of lymph node involvement is an important factor in evaluating the prognosis and therapeutic options for patients with RMS. The expression of Ki-67 has been demonstrated to be closely associated with the prognosis and clinical behaviors of soft tissue sarcomas and can thus help to identify patients at high risk of having an aggressive phenotype.^24,25 The prognostic value of Ki-67 in RMS remains unclear, and few relevant studies have been performed. Soffer et al. ²⁶ were the first to study the correlation between Ki-67 expression and imaging manifestations in RMS. They found that the Ki-67 value was correlated with the tumor size and lymph node metastasis. They concluded that the combination of Ki-67 expression and tumor size can be used as a predictor of lymph node spread, and the combination of Ki-67 expression of ≥60% and tumor size of ≥50 mm can usually predict the presence of lymph node metastasis. ²⁶ Our patient had very typical clinical symptoms and had not yet developed distant metastasis at the time of diagnosis; however, his Ki-67 positive index was >70%. The primary tumor was >10 cm in size and accompanied by regional lymph node metastasis. The patient had a very poor prognosis, surviving only 4 months after diagnosis. This outcome is consistent with the findings of the above-mentioned study. ²⁶

The standard treatment for prostate ERMS in adults remains to be defined. Radical surgery should be performed as early as possible for patients with limited disease, and radiotherapy and chemotherapy are important adjuvant treatments for patients with high-risk and advanced disease. ²⁷ The combination of vincristine, actinomycin D, and cyclophosphamide (VAC regimen) is still considered the standard chemotherapeutic regimen for ERMS. ²⁸ Sohn et al. ²⁹ reviewed the clinical outcomes of 20 adults with prostate sarcoma who underwent various modes of treatment, and their findings suggest that combination therapy offers a survival advantage over surgery or chemotherapy alone. In some cases, the combination of radiotherapy and chemotherapy resulted in progression-free survival of about 1 year (up to 49 months).^15,30,31 However, in a report by Johnson et al., ³² the patient barely responded to three cycles of VAC chemotherapy, radical surgery, and three palliative radiotherapy sessions and died 6 months after diagnosis. Our patient received one course of chemotherapy with the IE regimen followed by two courses of chemotherapy with other regimens, but he responded poorly to treatment regardless of the chemotherapy regimen. His tumor-specific survival was only 4 months, reflecting the highly aggressive nature of this pathologic type.

Conclusions

Prostatic RMS in men is rare and has a poor prognosis. Consideration of this rare differential diagnosis is crucial to avoid delaying appropriate treatment. If the morphology suggests SpRMS, patients should ideally undergo genetic testing for more precisely targeted medical treatment and prognostic assessment. Our study was limited by the lack of genetic testing of the patient’s tumor; nevertheless, this is a unique report of a rare prostatic spindle cell ERMS in an adult that exhibited an invasive clinical course.