Shiven Patel, MD

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.

A 70-year-old veteran followed in clinic for metastatic castration-resistant prostate cancer (mCRPC) was found to have a new left axillary lymph node conglomerate on routine imaging, despite stable PSA on Enzalutamide therapy. Biopsy of the axillary mass showed metastatic neuroendocrine carcinoma, with a differential diagnosis of small cell carcinoma of unknown primary vs. Merkel Cell Carcinoma (MCC). Given his prostate cancer diagnosis and the rarity of MCC, small cell differentiation of prostate cancer was initially favored. However, the patient appeared well and subsequent PET/CT only showed two subcutaneous hypermetabolic lesions. These findings would be unusual with small cell differentiation of prostate cancer. A second biopsy of a subcutaneous lesion was most consistent with MCC, confirming our diagnosis.

At time of diagnosis, staging MRI Brain revealed 3 parenchymal brain lesions, presumed to be metastatic MCC. As per a landmark trial by Nghiem et al, the patient was started on Pembrolizumab 2 mg/kg every three weeks for treatment of metastatic MCC. Brain lesions were locally treated with stereotactic radiosurgery (SRS).

Although his mCRPC was under good control with Enzalutamide, this drug is associated with increased risk of seizures in clinical trial and is not recommended for those with predisposing seizure risk. In light of MCC brain metastases, we decided to switch mCRPC therapy to Darolutamide, an androgen receptor antagonist that has lower penetration of the blood-brain barrier and less incidence of seizures. He tolerated the combination of Darolutamide with Pembrolizumab well, with only a grade 1 acneiform rash.

After just 1 cycle of Pembrolizumab, the patient’s clinically-evident MCC drastically regressed. After 8 months of treatment, his MCC continues to respond clinically and radiographically. This case emphasizes the importance of not relying on “Occam’s razor” – that one should assume a single diagnosis for multiple findings. The simplest explanation of the patient’s left axillary mass biopsy would have been small cell differentiation of prostate cancer; however, this has proved to be a synchronous MCC, which portends a much more favorable prognosis with immunotherapy treatment. We also demonstrate a successful approach to concurrent treatment of metastatic MCC and mCRPC.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

INTRODUCTION: Methylene blue (MB) has recently gained traction as an adjunctive therapy in the management of vasoplegia. Due to risk of inducing oxidative hemolysis its use should be avoided in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Although rare, drug induced oxidative hemolysis can still occur in patients without G6PD deficiency. In this report, we describe a case of severe oxidative hemolysis in a G6PD sufficient adult following administration of a large dose of MB.

CASE REPORT: A 78-year-old male with a history of coronary artery disease was admitted for coronary artery bypass graft surgery. Patient underwent surgery without any major complications. Post operatively however he developed severe shock refractory to multiple vasopressors and inotropes. A presumptive diagnosis of vasoplegia was made for which the patient was given multiple boluses of MB. Hemodynamics improved thus the patient was started on a MB infusion. Approximately 24 hours later the patient was noted to have an acute drop in his hemoglobin from 9.9 to 8.0 g/dl. He was transfused multiple units of blood with only transient improvements in his hemoglobin. Physical exam and imaging revealed no evidence of bleeding. Additional workup was notable for an LDH of 7222 U/L and an elevated bilirubin raising concern for hemolytic anemia.

Review of his peripheral smear was notable for the presence of numerous bite cells. A diagnosis of oxidative hemolytic anemia secondary to MB administration was made. MB infusion was discontinued and within 48 hours the patient’s LDH normalized and hemoglobin had stabilized. A quantitative G6PD test ordered during the acute hemolytic period and was reported as normal. Due to the possibility of a falsely normal result in the setting of active hemolysis, G6PD testing was repeated two months following discharge and was also normal.

CONCLUSIONS: Methylene blue can be a lifesaving medication in the setting of severe vasoplegia. However, clinicians should be aware of the possibility of inducing severe oxidative hemolytic anemia even in G6PD sufficient patients when giving this agent in large doses. Management of oxidative hemolysis secondary to MB is supportive care with prompt discontinuation resulting in resolution of hemolysis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive malignancy of predominantly B-cell origins. Where tolerated, strong sensitivity is seen with induction regimens containing high-dose methotrexate and rituximab. However, little is known regarding ideal therapy for T-cell variants, especially anaplastic large cell lymphoma.

CASE REPORT: A 20-year-old male with no past medical history developed progressive positional headaches, nausea, and dizziness over several months. Between several hospital visits, he was found to have enhancing lesions of his right caudate, left cerebellum, and right frontal lobe. A lumbar puncture demonstrated pleocytosis (152 WBC, 97% lymphocytes) and a small population of atypical CD5- T-cells on flow cytometry. Preliminary biopsy of the right caudate lesion was inconclusive, significant only for demyelination and a subset of LGL-like T-cells expressing CD3 and TIA-1. Neurology was consulted and he was given high-dose methylprednisolone with significant improvement in his symptoms. However, several months later he returned to the emergency department with new headaches, vomiting, and bilateral nystagmus. A repeat brian MRI showed lesion progression and evidence of hydrocephalus. He received hypertonic saline prior to external ventricular drain placement. Once stabilized, he underwent an uncomplicated left retrosigmoid craniotomy with resection of his cerebellar lesion. Histopathology demonstrated strong CD30 and ALK1 expression, with atypical mature T-cells on flow cytometry (CD4+, CD8+, CD5-). PET/CT imaging, bone marrow biopsy, and an ophthalmologic slit lamp exam were without evidence of systemic disease. He was given a diagnosis of PCNSL of T-cell origin (ALK+ anaplastic large cell subtype) and discharged on a dexamethasone taper. After surgical recovery he was started on induction chemotherapy with high-dose methotrexate, procarbazine, and vincristine (MPV). Interval MR imaging demonstrated marked decrease in the size of his intracranial lesions. He was subsequently transitioned to consolidation with HiDAC with the intent to undergo autologous hematopoietic cell transplant.

CONCLUSIONS: Incidence of ALK-positive anaplastic large cell PCNSL is extremely rare, and thus consensus data regarding optimal treatment is lacking. For younger patients with good functional status and renal clearance, induction therapy containing high-dose methotrexate (i.e. MPV) can provide an effective bridge to consolidation and autologous hematopoietic cell transplant.