Comprehensive genomic profiling of primary bladder mucinous adenocarcinoma, a rare genitourinary cancer: A case report

Abstract

Primary bladder mucinous adenocarcinoma is a rare genitourinary cancer. Here, we present the case of a 75-year-old woman where pathological and imaging findings led to the diagnosis of primary bladder mucinous adenocarcinoma. She underwent treatment with paclitaxel–ifosfamide–cisplatin (TIP). After two cycles of TIP therapy, FoundationOne CDx, a comprehensive genomic profiling test, was performed, revealing variants in ATM , SMAD4 , BRD4 , and NOTCH3 . These genomic profiling test results may lead to the development of novel therapeutic agents for primary bladder mucinous adenocarcinoma.

Highlights

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Primary bladder mucinous adenocarcinoma (PBA) is a rare genitourinary cancer.
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Reports on the genomic analysis of (PBA) are scarce.
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Comprehensive genomic profiling test of (PBA) revealed gene variants which may lead to development of novel therapy.

1 Introduction

Primary bladder adenocarcinoma (PBA), particularly the mucinous subtype, is rare, accounting for less than 2 % of all bladder malignancies. ^, An effective chemotherapy regimen has not been established and the most effective treatment is surgical resection, but the prognosis is generally poor. Although chemotherapy regimens combining 5-fluorouracil (5-FU) and cisplatin as well as regimens using folinic acid, fluorouracil, and oxaliplatin (FOLFOX) have been reported as effective, few reports have high levels of evidence. Recently, comprehensive genomic profiling tests have become available for use in clinical practice, and they are the tests of choice to determine the treatment plan for rare cancers. ^,

In this study, we report the results of FoundationOne CDx tests for primary bladder mucinous adenocarcinoma.

2 Case presentation

We report the case of a 75-year-old woman who was referred to our hospital. She had visited her previous urologist with a chief complaint of frequent urination and urinary incontinence. A broad-base tumor of the bladder with bilateral ureteral obstruction was identified, and left nephrostomy was performed. Transurethral resection of the bladder tumor was performed as a standby procedure, but complete resection was difficult, and only partial tumor resection was achieved. The patient was pathologically diagnosed with primary bladder mucinous adenocarcinoma ( Fig. 1 ) and referred to our hospital. Magnetic resonance imaging revealed an extensive mass bulge from the posterior wall of the bladder into the lumen, leading to the suspicion of extravesical extension and invasion into the uterus ( Fig. 2 A and B). Since the lesion was predominantly located in the bladder on imaging tests including cystoscopy, this tumor was considered as originating from the bladder. An ¹⁸ F-fluorodeoxyglucose-positron emission tomography/computed tomography scan showed multiple lymph node metastases in the para-aortic and internal iliac lymph nodes ( Fig. 2 C and D). Collectively, these findings led to the diagnosis of primary bladder mucinous adenocarcinoma (cT4N1M0). Because this cancer type is extremely rare and there is no established chemotherapy regimen, we selected the paclitaxel–ifosfamide–cisplatin (TIP) regimen for PBA reported by Galsky et al.. After the first cycle, the patient was diagnosed with stable disease (SD) and remained within the SD range after the second cycle, but lymph node metastases showed an increasing trend. Therefore, FoundationOne CDx was performed in parallel with the preparation for the third cycle of TIP. However, the patient was hospitalized for general malaise and abdominal distension before the third cycle could commence, and imaging showed disease progression, including peritoneal dissemination. The FoundationOne CDx tests detected pathogenic variants in several genes, including ATM , SMAD4 , BRD4 , and NOTCH3 ( Table 1 ), but due to the patient’s poor condition, these findings did not result in the initiation of any treatments that were expected to be effective. Later, the patient was provided with best supportive care and she subsequently died.