From B to T: a Case of Concurrent B-Cell and T-Cell Lymphomas Successfully Palliated With Targeted Therapies

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Background

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type of non- Hodgkin lymphoma (NHL), comprising 30% of all NHL. Due to a decreased state of immunosurveillance resulting from the disease itself and its associated therapies, patients are at increased risk of developing a secondary malignancy. Multiple primary malignancies have been reported to occur in up to 15% of patients with DLBCL, retrospectively.

Herein, we review a case of a man with DLBCL who concomitantly developed ALK negative anaplastic large cell lymphoma (ALCL) distinctly of T-cell lineage who was successfully treated with palliative therapy for both diagnoses despite his advanced age and diagnosis associated with a poor prognosis with continued effect and sustained quality of life.

Case Report

An 88-year-old man presented with stage III DLBCL, diagnosed in 12/2018, was deemed not to be an aggressive therapy candidate. As such, he was treated with Rituximab monotherapy for 6 cycles, ending in 02/2019, with remarkably good effect. He remained in a PR with stable disease on serial PET/CTs until 09/2021, at which time he was noted to have Horner’s Syndrome in clinic. CT chest demonstrated a right apical lung mass, not previously seen on prior scans measuring 4.2 x 2.7 cm. Other sites of nodal disease remained stable on PET/CT.

Biopsy of the lesion revealed CD30+ ALK-negative ALCL with distinct T-cell marker positivity on immunohistochemistry and the absence of B-cell lineage markers. After discussion at our treatment planning conference, we decided to treat with brentuximab-vedotin (Bv) monotherapy for 6 cycles. End of treatment PET/CT demonstrated a PR with near resolution in background PET avidity at the lesion. His symptoms of Horner syndrome also improved.

Conclusion

A diagnosis of aggressive lymphoma increases the risk of developing a secondary malignancy and providers should remain vigilant of this. Elderly individuals in whom aggressive therapies may be precluded can still greatly benefit from palliative targeted therapy even in the setting of diseases historically associated with a poor prognosis.

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Background

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type of non- Hodgkin lymphoma (NHL), comprising 30% of all NHL. Due to a decreased state of immunosurveillance resulting from the disease itself and its associated therapies, patients are at increased risk of developing a secondary malignancy. Multiple primary malignancies have been reported to occur in up to 15% of patients with DLBCL, retrospectively.

Herein, we review a case of a man with DLBCL who concomitantly developed ALK negative anaplastic large cell lymphoma (ALCL) distinctly of T-cell lineage who was successfully treated with palliative therapy for both diagnoses despite his advanced age and diagnosis associated with a poor prognosis with continued effect and sustained quality of life.

Case Report

An 88-year-old man presented with stage III DLBCL, diagnosed in 12/2018, was deemed not to be an aggressive therapy candidate. As such, he was treated with Rituximab monotherapy for 6 cycles, ending in 02/2019, with remarkably good effect. He remained in a PR with stable disease on serial PET/CTs until 09/2021, at which time he was noted to have Horner’s Syndrome in clinic. CT chest demonstrated a right apical lung mass, not previously seen on prior scans measuring 4.2 x 2.7 cm. Other sites of nodal disease remained stable on PET/CT.

Biopsy of the lesion revealed CD30+ ALK-negative ALCL with distinct T-cell marker positivity on immunohistochemistry and the absence of B-cell lineage markers. After discussion at our treatment planning conference, we decided to treat with brentuximab-vedotin (Bv) monotherapy for 6 cycles. End of treatment PET/CT demonstrated a PR with near resolution in background PET avidity at the lesion. His symptoms of Horner syndrome also improved.

Conclusion

A diagnosis of aggressive lymphoma increases the risk of developing a secondary malignancy and providers should remain vigilant of this. Elderly individuals in whom aggressive therapies may be precluded can still greatly benefit from palliative targeted therapy even in the setting of diseases historically associated with a poor prognosis.

Background

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive type of non- Hodgkin lymphoma (NHL), comprising 30% of all NHL. Due to a decreased state of immunosurveillance resulting from the disease itself and its associated therapies, patients are at increased risk of developing a secondary malignancy. Multiple primary malignancies have been reported to occur in up to 15% of patients with DLBCL, retrospectively.

Herein, we review a case of a man with DLBCL who concomitantly developed ALK negative anaplastic large cell lymphoma (ALCL) distinctly of T-cell lineage who was successfully treated with palliative therapy for both diagnoses despite his advanced age and diagnosis associated with a poor prognosis with continued effect and sustained quality of life.

Case Report

An 88-year-old man presented with stage III DLBCL, diagnosed in 12/2018, was deemed not to be an aggressive therapy candidate. As such, he was treated with Rituximab monotherapy for 6 cycles, ending in 02/2019, with remarkably good effect. He remained in a PR with stable disease on serial PET/CTs until 09/2021, at which time he was noted to have Horner’s Syndrome in clinic. CT chest demonstrated a right apical lung mass, not previously seen on prior scans measuring 4.2 x 2.7 cm. Other sites of nodal disease remained stable on PET/CT.

Biopsy of the lesion revealed CD30+ ALK-negative ALCL with distinct T-cell marker positivity on immunohistochemistry and the absence of B-cell lineage markers. After discussion at our treatment planning conference, we decided to treat with brentuximab-vedotin (Bv) monotherapy for 6 cycles. End of treatment PET/CT demonstrated a PR with near resolution in background PET avidity at the lesion. His symptoms of Horner syndrome also improved.

Conclusion

A diagnosis of aggressive lymphoma increases the risk of developing a secondary malignancy and providers should remain vigilant of this. Elderly individuals in whom aggressive therapies may be precluded can still greatly benefit from palliative targeted therapy even in the setting of diseases historically associated with a poor prognosis.

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Not Just Castleman Disease: an Elusive Diagnosis of TAFRO Syndrome

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Introduction

Idiopathic multicentric Castleman disease (iMCD) cases with thrombocytopenia (T), anasarca (A), Fever (F), reticulin fibrosis (R), and organomegaly (O) are considered a subtype of iMCS called TAFRO syndrome. It is a rare syndrome characterized by an acute clinical course and a poor prognosis. The optimal management of TAFRO syndrome is unclear. Treatment is predicated on case reports, which have used an assortment of agents including corticosteroids, cyclosporin, rituximab, and/or anti-IL-6 therapies such as tocilizumab or siltuximab.

Case Report 

A 73-year-old Japanese man recently diagnosed with iMCD but not currently on treatment presented with a 3-week history of worsening lower extremity edema and abdominal distension. On exam, he had anasarca and was also found to be anuric. Diagnostic testing was notable for hemoglobin 10.9 g/dL, platelets 42 K/uL, potassium 5.7 mmol/L, creatinine 3.7, albumin 2.4 g/dL, troponin 0.1, BNP 805, and Echocardiogram demonstrating an ejection fraction of 40% to 50%. Imaging revealed pleural effusion, splenomegaly and large volume ascites while paracentesis confirmed transudative ascitic fluid. He failed a trial of IV diuresis and was started on dialysis for refractory hyperkalemia. Upon review, his prior bone marrow had mild reticulin fibrosis, and additional lab testing showed an elevated hs-CRP 101 mg/dL and IL-6 of 4.8 pg/mL. His presentation fit multiple criteria for TAFRO including thrombocytopenia, anasarca, fibrosis in bone marrow, renal failure and organomegaly. He was started on weekly rituximab for 4 doses, as well as daily dexamethasone 40 mg for 4 days followed by a planned 6-week prednisone taper. Within a week his urine output began to improve, creatinine improved to 2 and he no longer needed dialysis.
Despite improvement in his renal function, he had progressive anasarca, fatigue and appetite loss over the next three weeks. He was given one dose of siltuximab as salvage therapy, but due to worsening quality of life, he transitioned to comfort care shortly thereafter with eventual demise.

Discussion

Determination of iMCD-TAFRO syndrome requires high clinical suspicion from clinicians to enable early treatment. This case report illustrates the need for early recognition and aggressive treatment to improve outcomes in patients with this deadly disease.

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Introduction

Idiopathic multicentric Castleman disease (iMCD) cases with thrombocytopenia (T), anasarca (A), Fever (F), reticulin fibrosis (R), and organomegaly (O) are considered a subtype of iMCS called TAFRO syndrome. It is a rare syndrome characterized by an acute clinical course and a poor prognosis. The optimal management of TAFRO syndrome is unclear. Treatment is predicated on case reports, which have used an assortment of agents including corticosteroids, cyclosporin, rituximab, and/or anti-IL-6 therapies such as tocilizumab or siltuximab.

Case Report 

A 73-year-old Japanese man recently diagnosed with iMCD but not currently on treatment presented with a 3-week history of worsening lower extremity edema and abdominal distension. On exam, he had anasarca and was also found to be anuric. Diagnostic testing was notable for hemoglobin 10.9 g/dL, platelets 42 K/uL, potassium 5.7 mmol/L, creatinine 3.7, albumin 2.4 g/dL, troponin 0.1, BNP 805, and Echocardiogram demonstrating an ejection fraction of 40% to 50%. Imaging revealed pleural effusion, splenomegaly and large volume ascites while paracentesis confirmed transudative ascitic fluid. He failed a trial of IV diuresis and was started on dialysis for refractory hyperkalemia. Upon review, his prior bone marrow had mild reticulin fibrosis, and additional lab testing showed an elevated hs-CRP 101 mg/dL and IL-6 of 4.8 pg/mL. His presentation fit multiple criteria for TAFRO including thrombocytopenia, anasarca, fibrosis in bone marrow, renal failure and organomegaly. He was started on weekly rituximab for 4 doses, as well as daily dexamethasone 40 mg for 4 days followed by a planned 6-week prednisone taper. Within a week his urine output began to improve, creatinine improved to 2 and he no longer needed dialysis.
Despite improvement in his renal function, he had progressive anasarca, fatigue and appetite loss over the next three weeks. He was given one dose of siltuximab as salvage therapy, but due to worsening quality of life, he transitioned to comfort care shortly thereafter with eventual demise.

Discussion

Determination of iMCD-TAFRO syndrome requires high clinical suspicion from clinicians to enable early treatment. This case report illustrates the need for early recognition and aggressive treatment to improve outcomes in patients with this deadly disease.

Introduction

Idiopathic multicentric Castleman disease (iMCD) cases with thrombocytopenia (T), anasarca (A), Fever (F), reticulin fibrosis (R), and organomegaly (O) are considered a subtype of iMCS called TAFRO syndrome. It is a rare syndrome characterized by an acute clinical course and a poor prognosis. The optimal management of TAFRO syndrome is unclear. Treatment is predicated on case reports, which have used an assortment of agents including corticosteroids, cyclosporin, rituximab, and/or anti-IL-6 therapies such as tocilizumab or siltuximab.

Case Report 

A 73-year-old Japanese man recently diagnosed with iMCD but not currently on treatment presented with a 3-week history of worsening lower extremity edema and abdominal distension. On exam, he had anasarca and was also found to be anuric. Diagnostic testing was notable for hemoglobin 10.9 g/dL, platelets 42 K/uL, potassium 5.7 mmol/L, creatinine 3.7, albumin 2.4 g/dL, troponin 0.1, BNP 805, and Echocardiogram demonstrating an ejection fraction of 40% to 50%. Imaging revealed pleural effusion, splenomegaly and large volume ascites while paracentesis confirmed transudative ascitic fluid. He failed a trial of IV diuresis and was started on dialysis for refractory hyperkalemia. Upon review, his prior bone marrow had mild reticulin fibrosis, and additional lab testing showed an elevated hs-CRP 101 mg/dL and IL-6 of 4.8 pg/mL. His presentation fit multiple criteria for TAFRO including thrombocytopenia, anasarca, fibrosis in bone marrow, renal failure and organomegaly. He was started on weekly rituximab for 4 doses, as well as daily dexamethasone 40 mg for 4 days followed by a planned 6-week prednisone taper. Within a week his urine output began to improve, creatinine improved to 2 and he no longer needed dialysis.
Despite improvement in his renal function, he had progressive anasarca, fatigue and appetite loss over the next three weeks. He was given one dose of siltuximab as salvage therapy, but due to worsening quality of life, he transitioned to comfort care shortly thereafter with eventual demise.

Discussion

Determination of iMCD-TAFRO syndrome requires high clinical suspicion from clinicians to enable early treatment. This case report illustrates the need for early recognition and aggressive treatment to improve outcomes in patients with this deadly disease.

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Waldenstrom Macroglobulinemia Presenting With Schnitzler Syndrome

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Background

Schnitzler syndrome is a rare, auto-inflammatory syndrome associated with IgM monoclonal gammopathy that manifests as a non-pruritic urticarial rash. Patients may also have intermittent fevers, lymphadenopathy, bone pain, and arthralgias. Given its rarity and nonspecific presentation, its diagnosis requires a high index of clinical suspicion. Herein, we describe a case of a patient with a 2-year history of urticarial rash who then developed fevers, arthralgias, neutrophilia, and weight loss. He was ultimately found to have a diagnosis of Waldenstrom Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL), in the context of Schnitzler Syndrome.

Case Report 

A 74-year-old traveling veteran presenting with fatigue, weight loss, arthralgias and rash was found to have anemia and leukocytosis concerning an occult hematologic malignancy. On exam, his rash appeared classically urticarial. He described the rash as nonpruritic and ‘waxing and waning’ for ~18 months. Following the rash, he developed drenching night sweats which progressively worsened over the last 4 months. This was accompanied by fatigue and arthralgias. On review of his labs, he had a normocytic anemia, thrombocytosis and progressive neutrophilia of approximately 20,000 over the last 4 months. Peripheral blood smear was remarkable for atypical lymphocytes. Peripheral blood flow cytometry revealed a small monoclonal CD5-/CD10- B-cell population of uncertain significance. His total serum IgM level was > 1000 mg/dL and serum protein electrophoresis with IFE confirmed a monoclonal IgM gammopathy with M-spike of 0.99 g/dL.

Results 

A bone marrow biopsy showed a hypercellular marrow with LPL comprising 50%-60% of the cellularity. It was also notable for grade 1/3 reticulin fibrosis and mild megakaryocytic aty WM/LPL can have a heterogeneous presentation. Urticarial rash, constitutional symptoms, joint pain, and neutrophilia should raise suspicion for Schnitzler syndrome, especially in conjunction with IgM monoclonal gammopathy. This rare syndrome is imperative to consider because it can be treated quickly with high efficacy with IL-1 antagonism. Anakinra is clinically effective for symptom management while awaiting primary treatment for underlying LPL.

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Background

Schnitzler syndrome is a rare, auto-inflammatory syndrome associated with IgM monoclonal gammopathy that manifests as a non-pruritic urticarial rash. Patients may also have intermittent fevers, lymphadenopathy, bone pain, and arthralgias. Given its rarity and nonspecific presentation, its diagnosis requires a high index of clinical suspicion. Herein, we describe a case of a patient with a 2-year history of urticarial rash who then developed fevers, arthralgias, neutrophilia, and weight loss. He was ultimately found to have a diagnosis of Waldenstrom Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL), in the context of Schnitzler Syndrome.

Case Report 

A 74-year-old traveling veteran presenting with fatigue, weight loss, arthralgias and rash was found to have anemia and leukocytosis concerning an occult hematologic malignancy. On exam, his rash appeared classically urticarial. He described the rash as nonpruritic and ‘waxing and waning’ for ~18 months. Following the rash, he developed drenching night sweats which progressively worsened over the last 4 months. This was accompanied by fatigue and arthralgias. On review of his labs, he had a normocytic anemia, thrombocytosis and progressive neutrophilia of approximately 20,000 over the last 4 months. Peripheral blood smear was remarkable for atypical lymphocytes. Peripheral blood flow cytometry revealed a small monoclonal CD5-/CD10- B-cell population of uncertain significance. His total serum IgM level was > 1000 mg/dL and serum protein electrophoresis with IFE confirmed a monoclonal IgM gammopathy with M-spike of 0.99 g/dL.

Results 

A bone marrow biopsy showed a hypercellular marrow with LPL comprising 50%-60% of the cellularity. It was also notable for grade 1/3 reticulin fibrosis and mild megakaryocytic aty WM/LPL can have a heterogeneous presentation. Urticarial rash, constitutional symptoms, joint pain, and neutrophilia should raise suspicion for Schnitzler syndrome, especially in conjunction with IgM monoclonal gammopathy. This rare syndrome is imperative to consider because it can be treated quickly with high efficacy with IL-1 antagonism. Anakinra is clinically effective for symptom management while awaiting primary treatment for underlying LPL.

Background

Schnitzler syndrome is a rare, auto-inflammatory syndrome associated with IgM monoclonal gammopathy that manifests as a non-pruritic urticarial rash. Patients may also have intermittent fevers, lymphadenopathy, bone pain, and arthralgias. Given its rarity and nonspecific presentation, its diagnosis requires a high index of clinical suspicion. Herein, we describe a case of a patient with a 2-year history of urticarial rash who then developed fevers, arthralgias, neutrophilia, and weight loss. He was ultimately found to have a diagnosis of Waldenstrom Macroglobulinemia (WM)/Lymphoplasmacytic Lymphoma (LPL), in the context of Schnitzler Syndrome.

Case Report 

A 74-year-old traveling veteran presenting with fatigue, weight loss, arthralgias and rash was found to have anemia and leukocytosis concerning an occult hematologic malignancy. On exam, his rash appeared classically urticarial. He described the rash as nonpruritic and ‘waxing and waning’ for ~18 months. Following the rash, he developed drenching night sweats which progressively worsened over the last 4 months. This was accompanied by fatigue and arthralgias. On review of his labs, he had a normocytic anemia, thrombocytosis and progressive neutrophilia of approximately 20,000 over the last 4 months. Peripheral blood smear was remarkable for atypical lymphocytes. Peripheral blood flow cytometry revealed a small monoclonal CD5-/CD10- B-cell population of uncertain significance. His total serum IgM level was > 1000 mg/dL and serum protein electrophoresis with IFE confirmed a monoclonal IgM gammopathy with M-spike of 0.99 g/dL.

Results 

A bone marrow biopsy showed a hypercellular marrow with LPL comprising 50%-60% of the cellularity. It was also notable for grade 1/3 reticulin fibrosis and mild megakaryocytic aty WM/LPL can have a heterogeneous presentation. Urticarial rash, constitutional symptoms, joint pain, and neutrophilia should raise suspicion for Schnitzler syndrome, especially in conjunction with IgM monoclonal gammopathy. This rare syndrome is imperative to consider because it can be treated quickly with high efficacy with IL-1 antagonism. Anakinra is clinically effective for symptom management while awaiting primary treatment for underlying LPL.

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