Janani Arunachalam, 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.