Olivia Steczko, MD

Background

Parotid gland malignancies are a rare subset of salivary gland tumors, comprising approximately 1–3% of all head and neck cancers. While distant metastases commonly involve the lungs, brain metastases are exceedingly rare and remain poorly characterized. Management typically includes stereotactic radiosurgery or whole-brain radiation. This study evaluates the incidence, clinicopathologic features, and survival outcomes of patients with parotid gland tumors and brain metastases using data from Surveillance, Epidemiology, and End Results (SEER) database.

Methods

SEER database (2010–2022) was queried for patients diagnosed with primary malignant neoplasms of the parotid gland (ICD-O-3 site code C07.9). Cases of brain metastases were identified using SEER metastatic site variables. Age-adjusted incidence rates (IR) per 100,000 population were calculated using SEER*Stat 8.4.5. Kaplan-Meier survival analyses were conducted using GraphPad Prism, and survival differences were assessed using the log-rank test.

Results

Among 12,951 patients diagnosed with parotid malignancy, 47 (0.36%) had brain metastases. The median age at diagnosis was 67 years, and 77.5% were male. The overall incidence rate (IR) of brain metastases was 0.00235 per 100,000 population, with a significantly higher rate observed in males compared to females (p < 0.0001). The most common histologic subtype associated with brain involvement was squamous cell carcinoma (SCC, n=10), followed by adenocarcinoma. Median overall survival (mOS) for patients with brain metastases was 2 months (hazard ratio [HR] 6.28; 95% CI: 2.71–14.55), compared to 131 months for those without brain involvement (p < 0.001). 1-year cancer-specific survival for patients with brain metastases was 38%. Among patients with parotid SCC and brain metastases, mOS was 3 months, compared to 39 months in those without brain involvement (HR 5.70; 95% CI: 1.09–29.68; p < 0.0001).

Conclusions

Brain metastases from parotid gland cancers, though rare, are associated with markedly poor outcomes. This highlights the importance of early neurologic assessment and brain imaging in high-risk patients, particularly with SCC histology. Prior studies have shown that TP53 mutations are common in parotid SCC, but their role in CNS spread remains unclear. Future research should explore molecular pathways underlying neurotropism in parotid cancers and investigate targeted systemic therapies with CNS penetration to improve outcomes.

Background

Parotid gland malignancies are a rare subset of salivary gland tumors, comprising approximately 1–3% of all head and neck cancers. While distant metastases commonly involve the lungs, brain metastases are exceedingly rare and remain poorly characterized. Management typically includes stereotactic radiosurgery or whole-brain radiation. This study evaluates the incidence, clinicopathologic features, and survival outcomes of patients with parotid gland tumors and brain metastases using data from Surveillance, Epidemiology, and End Results (SEER) database.

Methods

SEER database (2010–2022) was queried for patients diagnosed with primary malignant neoplasms of the parotid gland (ICD-O-3 site code C07.9). Cases of brain metastases were identified using SEER metastatic site variables. Age-adjusted incidence rates (IR) per 100,000 population were calculated using SEER*Stat 8.4.5. Kaplan-Meier survival analyses were conducted using GraphPad Prism, and survival differences were assessed using the log-rank test.

Results

Among 12,951 patients diagnosed with parotid malignancy, 47 (0.36%) had brain metastases. The median age at diagnosis was 67 years, and 77.5% were male. The overall incidence rate (IR) of brain metastases was 0.00235 per 100,000 population, with a significantly higher rate observed in males compared to females (p < 0.0001). The most common histologic subtype associated with brain involvement was squamous cell carcinoma (SCC, n=10), followed by adenocarcinoma. Median overall survival (mOS) for patients with brain metastases was 2 months (hazard ratio [HR] 6.28; 95% CI: 2.71–14.55), compared to 131 months for those without brain involvement (p < 0.001). 1-year cancer-specific survival for patients with brain metastases was 38%. Among patients with parotid SCC and brain metastases, mOS was 3 months, compared to 39 months in those without brain involvement (HR 5.70; 95% CI: 1.09–29.68; p < 0.0001).

Conclusions

Brain metastases from parotid gland cancers, though rare, are associated with markedly poor outcomes. This highlights the importance of early neurologic assessment and brain imaging in high-risk patients, particularly with SCC histology. Prior studies have shown that TP53 mutations are common in parotid SCC, but their role in CNS spread remains unclear. Future research should explore molecular pathways underlying neurotropism in parotid cancers and investigate targeted systemic therapies with CNS penetration to improve outcomes.

Background

Parotid gland malignancies are a rare subset of salivary gland tumors, comprising approximately 1–3% of all head and neck cancers. While distant metastases commonly involve the lungs, brain metastases are exceedingly rare and remain poorly characterized. Management typically includes stereotactic radiosurgery or whole-brain radiation. This study evaluates the incidence, clinicopathologic features, and survival outcomes of patients with parotid gland tumors and brain metastases using data from Surveillance, Epidemiology, and End Results (SEER) database.

Methods

SEER database (2010–2022) was queried for patients diagnosed with primary malignant neoplasms of the parotid gland (ICD-O-3 site code C07.9). Cases of brain metastases were identified using SEER metastatic site variables. Age-adjusted incidence rates (IR) per 100,000 population were calculated using SEER*Stat 8.4.5. Kaplan-Meier survival analyses were conducted using GraphPad Prism, and survival differences were assessed using the log-rank test.

Results

Among 12,951 patients diagnosed with parotid malignancy, 47 (0.36%) had brain metastases. The median age at diagnosis was 67 years, and 77.5% were male. The overall incidence rate (IR) of brain metastases was 0.00235 per 100,000 population, with a significantly higher rate observed in males compared to females (p < 0.0001). The most common histologic subtype associated with brain involvement was squamous cell carcinoma (SCC, n=10), followed by adenocarcinoma. Median overall survival (mOS) for patients with brain metastases was 2 months (hazard ratio [HR] 6.28; 95% CI: 2.71–14.55), compared to 131 months for those without brain involvement (p < 0.001). 1-year cancer-specific survival for patients with brain metastases was 38%. Among patients with parotid SCC and brain metastases, mOS was 3 months, compared to 39 months in those without brain involvement (HR 5.70; 95% CI: 1.09–29.68; p < 0.0001).

Conclusions

Brain metastases from parotid gland cancers, though rare, are associated with markedly poor outcomes. This highlights the importance of early neurologic assessment and brain imaging in high-risk patients, particularly with SCC histology. Prior studies have shown that TP53 mutations are common in parotid SCC, but their role in CNS spread remains unclear. Future research should explore molecular pathways underlying neurotropism in parotid cancers and investigate targeted systemic therapies with CNS penetration to improve outcomes.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Case Presentation

A 75-year-old man with chronic kidney disease, hypertension and diabetes mellitus presented with acute kidney injury (creatinine 5.2 from baseline 4.2) and a two-week history of increased urinary frequency. Labs revealed high anion gap metabolic acidosis, proteinuria, hematuria, pyuria, and acute on chronic anemia. He was diagnosed with kappa light chain nephropathy and multiple myeloma with 32% plasma cells on bone marrow biopsy. He began treatment with bortezomib, cyclophosphamide, and dexamethasone (Cy- BorD). Three days after cyclophosphamide and five days after bortezomib, the patient developed persistent hypotension with systolic BP in the 50s, unresponsive to fluids and Trendelenburg position. Due to end-stage renal disease with anuria, fluid resuscitation was limited. He required norepinephrine and was transferred to the ICU. Given instability, hemodialysis was deferred, and continuous renal replacement therapy was initiated. Shock evaluation included a CT abdomen showing enteritis versus ileus; however, infectious workup was negative. Cardiogenic shock was ruled out with a serial echocardiogram showing normal ejection fractions of 59-67% without significant valvular disease. The workup for adrenal insufficiency was negative. After the exclusion of other potential causes of shock, severe refractory hypotension was attributed to bortezomib toxicity.Hypotension is a known adverse effect of bortezomib. Orthostatic hypotension may occur in 8 to 9% of patients, and rarely, patients may experience heart failure, conduction disorders and arrhythmias, or cardiogenic shock. The pathologic mechanism of this toxicity is still poorly understood. Proposed mechanisms include direct endothelial toxicity as evidenced by thrombotic microangiopathy or impairment of sympathetic and parasympathetic nerve fibres. Most commonly, patients experience neurotoxicity, which may manifest as autonomic dysfunction or peripheral neuropathy. Cardiovascular complications are typically reversible. Our patient’s cardiac function remained within normal limits; therefore, his persistent hypotension was felt to be the result of direct toxicity from bortezomib rather than cardiogenic shock. Ultimately, blood pressure did improve, and vasopressors were discontinued. However, he continued to have orthostatic hypotension and continued to require supportive fludrocortisone, midodrine, and pyridostigmine. Goals of care have been discussed, and he wished to continue pursuing restorative care, with a plan for transition to carfilzomib versus daratumumab outpatient.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.