Benign Mimickers of Urinary Bladder Cancer: a Case Series

Abstract

Bladder cancer is one of the leading malignancies in the world associated with significant morbidity and mortality. However, several benign lesions of the bladder can mimic urothelial carcinoma clinically and radiologically owing to overlapping signs and symptoms. Thus, rendering a correct diagnosis is imperative as it will have a significant impact on the management of patients. We present an amalgamation of five cases having a high suspicion of urothelial malignancy, which were subsequently diagnosed as benign entities with better prognosis and thus warranted a different therapeutic approach.

Introduction

Bladder cancer is one of the most common urological malignancies. It is the seventh most common cancer in the world [1]. It is a disease of significant morbidity and mortality. Specimens from bladder are commonly encountered by a pathologist, and due to a significant therapeutic implication, emphasis is usually laid on neoplasms. Many non-neoplastic lesions of the bladder could potentially be confused for bladder cancer as these have similar presentations to cancer, as far as clinical manifestations and radiological features are concerned.

We present a series of five cases where the patients presented with clinical features of bladder cancer. Radiology and cystoscopy hinted at a possible malignancy for which the patients underwent further biopsies, which on histology turned out to be benign lesions.

Case 1

An 84-year-old man presented with low-grade fever and increased urinary frequency with poor flow for 1 month. He had no dysuria or hematuria. Digital rectal examination showed grade III benign non-tender prostate gland. Given the age at presentation, obstructive uropathy was suspected. The total leucocyte count was 13,300/mcl and a PSA level of 34.91 ng/ml. Ultrasonography (USG) was done which revealed a large prostate (103 g) with hypoechoic areas suggestive of abscess and a thick walled bladder. A provisional diagnosis of prostatic abscess was rendered. MRI and CECT were done for confirmation which showed an enhancing lesion at the dome of the bladder (Fig. 1a). Bladder mass FNA was done which showed only blood and was unsatisfactory for comment. A partial cystectomy was planned since cystoscopy and biopsy were deemed difficult due to elongated prostatic urethra, a large prostate, and location of the mass.

Fig. 1.

a–c Axial T2W MR image showing a well-defined heterogeneous signal intensity lesion is noted arising from the anterior wall of the urinary bladder and projecting into the lumen (a). Photomicrograph showing large channels lined by endothelial cells (HE × 200) (b). Photomicrograph showing amorphous deposits of extracellular eosinophillic material (× 200) (c). Stain for methyl violet highlighting the amyloid deposits (d)

On gross examination of the specimen, external surface was smooth and congested. Mucosal aspect had a dome-shaped elevation measuring 5.5 × 4 cm. Cut surface of the lesion was spongy with blood clots. Microscopic examination showed large, variably sized cystically dilated vessels with thickened walls, lined by a single layer of endothelium infiltrating the bladder muscle (Fig. 1b). A diagnosis of cavernous hemangioma of the bladder was made.

Case 2

A 43-year-old man presented with complaints of recurrent hematuria and mild dysuria for 18 months. Abdominal USG showed thickened urinary bladder wall, possibly neoplastic which was followed by cystoscopy and bladder biopsy. The biopsy showed hemorrhagic cystitis. The patient was treated symptomatically, but he continued to have symptoms. The patient was reevaluated at our hospital where a repeat biopsy was carried out. On histopathology, the biopsy showed masses of acellular, eosinophilic proteinaceous material in the lamina propria (Fig. 1c) which stained positive for methyl violet (Fig. 1d) and Congo red. A diagnosis of urinary bladder amyloidosis was made.

Case 3

A 35-year-old female presented with complaints of lower urinary symptoms in the perimenstrual periods for 2 years. There were no complaints of hematuria. She had undergone two cesarean deliveries, the last being 3 years back. Urine cytology was negative for malignant cells. USG of the pelvis showed a 4-mm hypoechoic lesion near the right vesico-ureteric junction. Cystoscopy demonstrated a bluish 2 × 2 cm polypoidal mass on the posterior wall of the bladder. This was followed by biopsy of the lesion which revealed thickened transitional cell mucosa along with some papillary structures with rare mitosis. A diagnosis of papillary urothelial neoplasm of low malignant potential was given. She underwent a trans-urethral resection of bladder tumor [TURBT]. Histopathological evaluation of the sections from the bladder tumor showed mild loss of polarity of the urothelial lining and loss of umbrella cells. At some foci in the subepithelium, endometrial type of glands and stroma were appreciated. The deep muscle included in the biopsy also showed endometrial foci (Fig. 2 a and b). A diagnosis of endometriosis of urinary bladder was given.

Fig. 2.

a–d Photomicrograph showing endometrial glands surrounded by stromal cells (a) and hemosiderin laden macrophages (b) (HE × 100 and HE × 200). Photomicrograph showing necrotic material with entrapped fungal organisms which are slender and aseptate (HE × 100) (c). GMS stain highlighting the fungal organisms (d)

Case 4

A 65-year-old man with a history of diabetes mellitus underwent renal transplant 5 months back. He was on immunosuppressive medications. The patient presented with severe urgency, frequency, and nocturia. Urinalysis showed hematuria and sterile pyuria. The urine culture was negative for bacterial growth but showed growth of fungal species. A cystoscopy was done to rule out other causes of hematuria, and it revealed a slightly friable, gray-brown mass measuring 0.8 × 0.6 cm in the posterior wall of the bladder. The biopsy of the lesion showed long, slender, septate fungal hyphae with acute angle branching which stained by Gomori silver methenamine. The background was necrotic. A diagnosis of bladder aspergillosis was rendered (Fig. 2 c and d).

Case 5

A 47-year-old woman presented with two episodes of painless hematuria within a month. The second episode was associated with postvoiding syncope and palpitations. Urine cytology for malignant cells was negative. USG showed a mass on the right lateral wall of the bladder measuring 1.8 × 1.5 cm. Cystoscopy revealed a smooth, well-vascularized mass on the right lateral wall of the bladder. Being suspicious for malignancy, the patient underwent TURBT. However, during surgery, her blood pressure spiked up to 230/112 mmHg and pulse rate dropped to 43/min. The patient was managed by antihypertensives. Postoperative recovery was uneventful.

Histological examination showed presence of polygonal cells arranged in zellballen pattern, separated by vascularized fibrous septa. The cells had centrally located nuclei with clumped chromatin and moderately fine granular cytoplasm. The cells on immunohistochemistry were positive for synaptophysin and chromogranin (Fig. 3 a, b, and c). These features were consistent with a diagnosis of paraganglioma.

Fig. 3.

a–c Photomicrograph showing tumor arranged in nests separated by stellate cells (HE × 100) (a). IHC for synaptophsyin (b) and chromogranin (c) showing positive staining (IHC × 100)

Discussion

Hemangioma of the urinary bladder is rare, with less than 100 cases reported in the literature [2]. They have a male preponderance, and the age at presentation ranges from 19 to 85 years [1].The most common presenting complaint is recurrent hematuria, others being suprapubic pain due to vesical irritation and urinary retention [2]. Our patient presented with voiding difficulties with increased frequency of micturition. There is a predilection for posterior and lateral walls. The tumor is usually single and small (< 3 cm) [2].Due to the usual presentation of recurrent painless hematuria with solitary tumor in the bladder wall, carcinoma of the bladder is generally suspected, especially in elderly patients; this entity needs to be ruled out.

Amyloidosis is a disorder of protein metabolism characterized by extracellular deposition of abnormal protein fibrils [3]. It may either be localized or systematic in distribution. Amyloidosis of the genitourinary tract is a rare entity, and isolated primary amyloidosis of the urinary bladder is even more uncommon with only about 200 cases reported in the literature [3]. Almost all patients present with painless hematuria. Amyloidosis may masquerade as urothelial carcinoma on cystoscopy and radiology [3]. Therefore, histopathological studies are imperative to arrive at the correct diagnosis.

Urinary tract is involved by endometriosis in 0.3–12% cases, out of which urinary bladder is a common site [4]. It can be primary or secondary. The former occurs spontaneously as a form of generalized pelvic disease. The secondary form usually occurs following operative procedures and is iatrogenic [5].

Migratory, metaplastic, and embryonal theories have been proposed to explain the underlying pathogenesis [5].In most of the cases, the symptoms include increased urgency and dysuria in the perimenstrual period. Cyclical hematuria occurs in 20% of the cases, which is pathognomonic for this entity [4, 5].

Aspergillus are a group saprophytic fungi which may infect the immunocompromised patients; however, infections in immunocompetent individuals have been reported [6]. Localized disease is much more uncommon than disseminated involvement; in the urinary tract, kidney is the most commonly involved, with few reports of bladder involvement. The most commonly involved organ being the lung, pulmonary symptoms are the most common. Bibler et al. reviewed 11 patients with aspergillomas of the renal system. Ten of these had an underlying disease that predisposed to the fungal infection. In immunocompromised patients, varying manifestations in the form of aspergillus, bezoars, ureteric obstruction, ureteric colic, renal failure, sepsis, or disseminated aspergillosis have been reported [7]. Our patient’s symptoms were unique, which he presented with hematuria and irritative voiding symptoms which prompted the need for cystoscopy and biopsy which later turned out to be fungal infection.

Paraganglioma of the urinary bladder are thought to arise from chromaffin cell rests in the bladder. These are uncommon in the bladder, accounting for 0.05% of all bladder tumors [8]. These may be functional or non-functional. In functional tumors, symptoms are due to excessive release of catecholamines leading to hypertensive crises. Post voiding palpitations and syncope are also common as in our patient [8, 9]. Hematuria is present in about 60% of patients [10]. CT and MRI are useful to localize the tumor and detect metastasis if any.

Conclusion

This case series emphasizes the accurate histological examination of the benign lesions of urinary bladder for final diagnosis. A good command of these lesions will help diagnose benign mimickers from malignant neoplasms and help guide the urologist to choose appropriate therapy and follow-up for the patient.