Metastatic cardiac tumor resulting in cardiogenic shock from muscle-invasive urothelial carcinoma of the bladder: a case report

Abstract

Muscle-invasive bladder cancer (MIBC) with cardiac metastasis typically carries a very poor prognosis. A Black woman in her 70s developed high-grade urothelial carcinoma with squamous differentiation invading the bladder muscle. Despite chemotherapy, radiation, and nephrostomy, the disease progressed. Six months after diagnosis, imaging revealed metastases to the heart and liver with biopsy showing a rare p63-positive, CK7-negative phenotype. Following a single dose of pembrolizumab, she died within three weeks, likely from cardiogenic shock. In CK7-negative variant urothelial carcinoma, early cardiac imaging and expanded immunohistochemical panels may improve detection of atypical metastases.

1. Background

Muscle-invasive bladder cancer (MIBC) invades the muscularis propria and frequently metastasizes. The standard treatment is radical cystectomy with bilateral pelvic lymph node dissection, while trimodal therapy (maximal TURBT plus concurrent chemoradiation) may be offered to patients seeking bladder preservation or those unfit for surgery.¹ Cardiac metastasis from MIBC, though rare, is associated with severe complications, including complete atrioventricular block, myocardial rupture, and cardiac tamponade, each contributing to significant morbidity and mortality in affected individuals.2, 3, 4, 5, 6, 7 Urothelial-derived cardiac metastases are very uncommon—only about thirty cases have been reported since 1934. Among these, most cases occurred in men, and were diagnosed postmortem.^2,3 This case illustrates the rare but severe nature of MIBC with cardiac metastasis, demonstrating CK7 negativity, contrasting from recent reports that highlight CK7 positivity as highly sensitive for cardiac metastatis. We aim to highlight the diagnostic and management challenges of this atypical phenotype and discuss the clinical implications and potential future strategies for treating this exceptionally rare presentation.

2. Case report

2.1. Initial presentation and diagnosis

A Black female in her 70s with Chronic Kidney Disease Stage IIIa (CKD IIIa), Type 2 Diabetes Mellitus (T2DM), Chronic Obstructive Pulmonary Disease (COPD), and a smoking history presented with dull abdominal and back pain, unexplained weight loss, difficulty urinating, and hematuria. An ultrasound initially showed a left adnexal mass with mild left hydronephrosis, and follow-up CT scan confirmed an 8 cm hyperdense obstructing bladder mass with bladder wall thickening and left-sided hydronephrosis. Bimanual exam revealed a firm, but not fixed mass.

2.2. Surgical and medical management

The patient underwent cystoscopy to evacuate symptomatic retained clots, followed by TURBT for diagnostic tissue sampling, which revealed a 6.5 cm solid, densely cellular tumor involving the left bladder floor and lateral wall while vaginoscopy showed no evidence of tumor invasion. Histopathology was consistent with invasive high-grade urothelial carcinoma demonstrating squamous differentiation and detrusor invasion. She was admitted for left percutaneous nephrostomy (PCN) tube placement to relieve the hydronephrosis. MRI one month later showed tumor progression of locally advanced T4 bladder cancer involving multiple surrounding structures and she was started on chemotherapy with cisplatin and gemcitabine. She developed neutropenia, and despite altering her regimen to carboplatin, she continued to have hematologic side-effects and subsequently began chemoradiation treatments with gemcitabine. Despite a left PCN tube to relieve her obstructive uropathy, and continuation of chemotherapy and radiation therapy, her condition progressively deteriorated over the following five months, marked by steadily worsening renal function.

2.3. Onset of cardiac symptoms and imaging

Six months after the original bladder cancer diagnosis, the patient presented to the ED with new onset chest pain. She was subsequently hospitalized and found to have severe anemia and mildly elevated troponin, and underwent a Transthoracic Echocardiogram (TTE), which revealed decreased cardiac function and an abnormal mass within the right ventricle (RV). Shown in Fig. 1, a CT positron emission tomography (PET) scan revealed hypermetabolic lesions in the liver and hilar lymph nodes, along with a markedly hypermetabolic contour of the anterior right ventricle, findings strongly suggestive of metastatic spread in the context of her known bladder cancer. The patient subsequently underwent an interventional radiology–guided liver biopsy, which confirmed metastatic urothelial carcinoma with focal squamous differentiation. A repeat TTE revealed a new effusion, smaller RV cavity, and lower LV stroke volume.

Fig. 1.

legend: PET/CT images depicting a right ventricular lesion with maximum standardized uptake value (SUVmax) of 20.9, consistent with metastatic disease in the setting of known bladder cancer. Adjacent suprahilar lymph nodes show moderate uptake (SUVmax up to 4.1), two ill-defined pulmonary nodules are also present: a 7 × 5 mm lesion in the anteromedial right upper lobe (SUVmax 5.6), and a 6 mm nodule at the right lung apex (SUVmax 1.9).

2.4. Final course and outcome

Given her documented distant metastases, she was initiated on pembrolizumab for palliative immunotherapy but only received one cycle. Three weeks from initial cardiac symptom onset, the patient died, likely from cardiogenic shock secondary to cardiac metastases and interval development of pericardial effusion.

3. Discussion

This report of a black female in her 70s with cardiac metastasis from primary muscle-invasive urothelial carcinoma is unique for several reasons. First, it contributes to further the understanding of the course that cardiac metastasis takes in the female population. A recent review noted a striking predominance of cardiac metastases in male patients, with most cases identified only at autopsy.³ Second, the absence of CK7 expression in our patient—a marker commonly positive in urothelial carcinoma—contrasts with prior reports in which CK7 along with AE1/AE3 demonstrated 100 % immunohistochemical sensitivity in cardiac metastases from urothelial carcinoma.³ In our patient's case, tumor cells from liver biopsy were positive for p63 and negative for CK7 while AE1/AE3 testing was not performed. The absence of CK7 expression in our patient underscores the necessity for further validation of CK7 and other potential biomarkers in detecting metastatic spread. Our findings emphasize the importance of maintaining a high index of suspicion for metastasis, even in the absence of expected immunohistochemical markers. Although p63 positivity has been documented in previous urothelial cardiac metastasis cases, its detection is non-specific and should be interpreted in the context of a broader immunohistochemical panel rather than in isolation. Despite the immunohistochemical marker discrepancies observed in this case, the potential of molecular markers to enhance the screening and diagnosis of metastatic cancers originating from muscle-invasive bladder cancer (MIBC) remains significant.

3.1. Mechanistic insights into the rarity of cardiac metastasis in urothelial carcinoma

While rare, secondary cardiac metastasis from UCC is particularly challenging due to the heart's unique environment, attributed to its unique lymphatic system and high-pressure environment, making tumor adherence and colonization difficult.8, 9, 10, 11 In this specific case, the likely route of cardiac metastasis was hematogenous spread, given the endocardial involvement as suggested by the location of the RV mass seen on echocardiogram and the location of altered SUV seen on PET scan. Given that lymphatic drainage occurs from the endocardium outwards to the epicardium, endocardial metastases are more commonly linked to hematogenous spread, while myocardial and epicardial metastases may arise from retrograde lymphatic flow.¹² UCC typically metastasizes via lymphatic or hematogenous routes to sites such as lymph nodes, liver, lungs, bones, and peritoneum.8, 9, 10, 11^,13, 14, 15 Several molecular factors likely contributed to the metastatic pathway observed in this patient with UCC. Epithelial-mesenchymal transition (EMT), a process that enhances tumor cell mobility and invasiveness, plays a critical role in the spread of cancer. Additionally, the loss of p63 function, a key driver of increased metastatic potential, further facilitates the spread of cancer to distant organs. These molecular alterations, including the downregulation of cadherin CDH-1, likely preceded the formation of cardiac tumor implants.⁹

3.2. Cardiac metastasis from urothelial carcinoma: disease course and poor prognosis

Cardiac metastases from muscle-invasive bladder cancer (MIBC) are challenging to diagnose due to their rarity and nonspecific presentation.¹⁰ Patients often remain asymptomatic or exhibit generalized symptoms such as fatigue, weight loss, or dyspnea, leading to delayed or missed diagnoses, frequently identified only at autopsy. When symptoms do manifest, they often mimic more common cardiac conditions, further complicating detection. Given the low incidence of cardiac involvement in urothelial carcinoma, clinicians may not readily suspect metastatic spread to the heart. Implementing early screening with echocardiography in high-risk MIBC patients could enhance early detection and improve outcomes.

In their literature review encompassing 30 patient case studies, De Araujo Souza et al. (2023) reported a mean survival duration of 60.69 days following the diagnosis of cardiac metastasis in male patients (77.78 % of the study population).³ Similar to this case, other cases have also shown a delay between diagnosis and treatment of UCC, where patients showed delayed onset of cardiac symptoms, and the diagnosis of heart metastasis is made.

3.3. Histologic variants of urothelial carcinoma

Despite an initially asymptomatic period, the abrupt clinical decline with the appearance of cardiac metastases reflects an advanced and aggressive disease course. Urothelial carcinoma with squamous differentiation presents in approximately 20 % of cases and tends to present at higher stage, exhibits poorer chemotherapy response, and carries significantly worse survival and shorter metastasis-free interval (median ∼3 months) compared to pure urothelial carcinoma (median ∼12 months).^16,17 Accordingly, in cases of urothelial carcinoma with squamous differentiation, early metastatic spread is possible and should trigger heightened clinical suspicion. Future research may consider tailored management strategies based on specific histologic variants of urothelial carcinoma.

4. Conclusion

This case underscores that cardiac metastasis from muscle-invasive urothelial carcinoma, even in the absence of common markers like CK7, represents an exceptionally rare but devastating manifestation, often associated with rapid clinical decline and poor prognosis. Urothelial carcinoma exhibiting squamous differentiation correlates with more advanced stage at presentation and shorter cancer-specific survival and recurrence-free intervals. Variant histology also increases early recurrence risk and may confer relative resistance to standard therapies. Thus, clinicians managing bladder cancer with squamous or other variant histology should maintain a high index of suspicion for early and even unusual site metastases, including to the heart, particularly when patients develop new cardiac or nonspecific systemic symptoms within months of diagnosis. Routine surveillance strategies in MIBC could incorporate early baseline cardiac imaging (e.g. TTE) and advanced modalities, especially in patients with high-risk histologic variants, to allow for timely detection of occult metastases.

CRediT authorship contribution statement

Logan Wesemann: Writing – review & editing, Writing – original draft, Visualization, Conceptualization. Brian Thomas: Writing – review & editing, Writing – original draft, Supervision, Conceptualization. Daniel Kim: Supervision, Conceptualization. Zachariah Taylor: Writing – review & editing, Writing – original draft, Supervision, Conceptualization. Matthew McCoo: Writing – review & editing, Conceptualization. Gregory C. McMahon: Supervision.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.