Gross hematuria secondary to vesicular varices: an unusual long-term sequela of inferior vena cava ligation and resection case report

Abstract

Extragonadal germ cell tumor may present with gross hematuria, resultant from the primary tumor, direct invasion, or metastatic involvement. This report describes gross hematuria occurring as a long-term sequela of EGGCT management. The patient in question had a documented history of an EGGCT, underwent chemotherapy with RPLND and resection of the IVC. Six years post-surgery, the patient exhibited gross hematuria. CT imaging demonstrated dilation of the vesical venous plexus with cystoscopic examination confirming prominent submucosal veins near the bladder neck. Gross hematuria is attributed to the spontaneous rupture of these veins, with spontaneous resolution.

1. Background

Hematuria, whether gross or microscopic, represents a prevalent chief complaint among urologic patients. The differential diagnosis encompasses numerous benign conditions, including genitourinary infections, inflammation, trauma, and hematologic disorders. Nonetheless, it is imperative that hematuria is thoroughly evaluated, as it can indicate a potential genitourinary malignancy in up to 25 % of cases.¹ In patients presenting with microscopic hematuria, the occurrence of malignant etiologies is less frequent, with approximately 1 % attributable to genitourinary malignancy. Among the 8 % of individuals with gross hematuria for whom no identifiable cause is established, approximately 18 % may subsequently develop urologic malignancy.² Furthermore, gross hematuria may serve as a precipitating sign of cancer recurrence in patients with a prior history of genitourinary malignancy.

Numerous reports have highlighted hematuria as an atypical presenting symptom of GU malignancy.3, 4, 5 However, a comprehensive review of the literature has not revealed any documented instances of hematuria as a long-term sequela of treatment of such tumors. The subsequent case presentation will demonstrate an unusual mechanism of hematuria in a patient with a history of EGGCT.

2. Case report

A 49-year-old Caucasian male presented with recurrent episodes of gross hematuria, which he first observed approximately three months prior to this consultation. During a recent prior emergency visit for similar symptoms, he underwent a non-contrast computed tomography (CT) scan that identified perivesicular fat stranding (Fig. 1, Fig. 2) and a non-obstructing stone in the left kidney. He received treatment for cystitis with a course of antibiotics; however, he continued to experience episodes of gross hematuria. At the time of his urological evaluation, urinalysis indicated hematuria without any signs of a urinary tract infection. A comprehensive review of the patient's medical records revealed a history of recurrent epistaxis, lower extremity edema, and stasis dermatitis. The patient otherwise reported no additional bothersome lower urinary tract symptoms.

Fig. 1.

Coronal plane of CT abdomen pelvis with contrast where perivesicular collateralization is noted. The most dilated vessels located along the lateral left bladder are denoted with the arrow. Other smaller, less obvious vessels are seen near the left bladder neck and diffusely on the right external bladder.

Fig. 2.

Transverse plane of CT abdomen pelvis with contrast denoting perivesicular collateralization. Again, the most prominent vessels are denoted by the arrow. Smaller vessels are less appreciated in this view in comparison to Fig. 1.

Upon further review of the patient's medical history, a notable urologic background was identified. Six years prior, the patient presented to the emergency department with abdominal pain and constipation persisting for several months. An abdominal ultrasound conducted at that time revealed a 15 cm retroperitoneal mass that displaced the aorta from the vertebral column and encased both the aorta and the inferior vena cava (IVC). A CT-guided biopsy subsequently confirmed the diagnosis of a mixed germ cell tumor. Additionally, a scrotal ultrasound revealed bilateral microlithiasis in atrophied testes; however, no discrete testicular lesion indicative of malignancy was detected. Tumor markers, specifically alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG), were found to be elevated. Testicular biopsy was not performed. The patient underwent four cycles of chemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP). Follow-up imaging demonstrated the persistence of masses surrounding the great vessels, despite the normalization of tumor markers. Consequently, the patient underwent a retroperitoneal lymph node dissection (RPLND) accompanied by vena cava resection, which was executed at an external facility.

The patient has been under surveillance since undergoing RPLND and vena cava ligation for the assessment of potential recurrence of mixed germ cell tumor. This surveillance protocol involves biannual clinical examinations, scrotal ultrasonography, tumor marker evaluations, and annual abdominopelvic imaging. Over this period, the clinical examinations, particularly the scrotal assessments, have consistently yielded benign results. The only abnormal finding identified during the recent evaluation for hematuria is the presence of bilateral varicoceles, with the left side being more pronounced than the right. On further review of the recent abdominopelvic imaging, we identified an increase in venous collateralization, which had been inaccurately classified as perivesicular fat stranding.

Considering the above-mentioned information and the necessity for hematuria evaluation, we conducted a cystoscopy on the patient. No concerning urologic findings were noted, although the flexible cystoscopy revealed dilated and prominent submucosal veins located near the bladder neck, consistent with the increased venous collateralization noted in the CT imaging. Ultimately, the analysis of urine cytology did not indicate any concerning findings, as well.

3. Discussion

Although germ cell tumors primarily develop within the testis, it is noteworthy that approximately 5 % of these tumors arise extragonadally.⁶ EGGCT, while less prevalent, exhibit an incidence rate ranging from 1.8 to 3.4 cases per million individuals.⁷ These tumors predominantly manifest in the mediastinum, retroperitoneum, and brain, though there have also been documented cases in genitourinary organs, such as the bladder, prostate, and kidneys.⁸

Our patient initially presented at the age of 43 with a 15 cm retroperitoneal mass, without an identifiable testicular mass. A CT-guided biopsy confirmed the diagnosis of a mixed germ cell tumor. The patient underwent chemotherapy, followed by a retroperitoneal lymph node dissection (RPLND) and inferior vena cava (IVC) resection. Currently, the patient is in active surveillance, which includes regular testicular ultrasounds and CT scans, all of which have yielded negative results to date. Notably, there are documented cases of EGGCT occurring in significant genitourinary (GU) organs, such as the seminal vesicles and kidneys that can lead to symptomatic bleeding.⁴ Furthermore, published literature indicates instances of testicular tumors that present with gross hematuria.^3,5 A patient with a historical diagnosis of malignancy presents a heightened concern for a malignant etiology of gross hematuria. Fortunately for our case patient, the subsequent workup was free of malignancy, instead revealing abnormal vascular formations. Specifically, vesicular collateral vascularization (venous plexus hypertension) was observed, primarily focused in the submucosal region. This abnormal vascularization is hypothesized to be the underlying cause of our patient's hematuria, as collateral vascularization in these areas is more susceptible to rupture.

Despite undergoing chemotherapy, the presence of residual masses adjacent to the aorta and inferior vena cava necessitated surgical intervention for their removal. In cases where the masses cannot be separated from the vessels, vascular intervention is not uncommon and occurs in approximately 6 % of patients with residual retroperitoneal tumor.^9,10 Furthermore, research conducted by Quinones-Baldrich et al. highlights that approximately 81 % of patients presenting with retroperitoneal tumors and suspected involvement of the inferior vena cava undergo some form of surgical resection of the IVC.¹¹ While management strategies following IVC resection, whether involving reconstruction or not, remain a topic of debate, it is imperative to acknowledge the significant role that vascular intervention may play in addressing potential downstream urological complications that may require further assessment or intervention.

Following the resection of the IVC, vascular collateralization begins if it had not already done so because of malignant obstruction. In instances of chronic obstruction of the vena cava, the establishment of vascular collateralization is essential for preserving venous drainage.

Our patient developed considerable collateral vascularization, as evidenced by the presence of bilateral varicoceles and pronounced lower extremity edema. Despite the inherent complexity and variability within pelvic venous anatomy, collateralization generally occurs through several well-documented pathways. These pathways include the deep pathway, consisting of the lumbar and sacral veins as well as the vertebral venous plexus; the superficial pathway, comprised of the circumflex and epigastric vessels; and the intermediate pathway, featuring the gonadal veins alongside the ovarian and uterine plexuses. Furthermore, there exist portosystemic pathways and various iliofemoral collateral pathways.¹² In this specific patient, significant perivesical vascularization was identified on computed tomography imaging and was visually apparent during cystoscopy. A review of the common collateral pathways does not specifically reference perivesical collateralization; however, it may be categorized under the intermediate pathway as outlined by Zurcher et al. Additionally, collateralization of bladder vessels is infrequent, even among patients with portal hypertension, a condition with well-recognized collateralization pathways. Although there have been reports of hematuria in patients with portal hypertension, the precipitating factors in those cases differ from those observed in the current patient.^13,14 The etiology of this patient's hematuria is relatively uncommon; however, similar cases have been documented that involve various pathological mechanisms. Considering the patient's history of an extragonadal germ cell tumor and the long-term sequelae associated with its management, the manifestation of hematuria is particularly noteworthy, rendering this case unique.

Thus far, the patient has not exhibited any episodes of intractable hematuria or recurrence of a mixed germ cell tumor. The patient will continue to conduct regular self-examinations and undergo scrotal ultrasounds to facilitate ongoing surveillance. With respect to the hematuria, no additional surveillance is required at this time following a negative evaluation. We have devised a plan to pursue chemical or surgical cauterization should there be any indication of intractable hematuria. Alternative options may include super selective embolization.

CRediT authorship contribution statement

Dillon J. Prokop: Writing – review & editing, Writing – original draft. Sumit Saini: Writing – review & editing, Investigation, Conceptualization. Goutham Vemana: Writing – review & editing, Supervision, Investigation.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.