Oncology

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract, accounting for approximately 1–2% of GI cancers. Hypoglycemia in patients with GIST is an uncommon and diagnostically challenging presentation, often involving a broad differential diagnosis. This case report explores the diagnostic difficulties encountered in managing persistent hypoglycemia in a patient with a history of advanced GIST.

Case Presentation

An 80-year-old male with a history of stage IV GIST, diagnosed in 2010, presented with persistent symptomatic hypoglycemia. His medical history included extensive abdominal disease, managed with multiple interventions: esophagogastrostomy, left lateral liver resection, a Whipple procedure, and Y-90 radioembolization. He received adjuvant imatinib therapy, which was discontinued in April 2024 due to significant adverse effects, including anasarca. In 2025, the patient developed progressive hypoglycemia, ultimately requiring continuous D10 infusion to maintain euglycemia, prompting an endocrinology evaluation. The initial diagnostic workup included cortisol, insulin, C-peptide levels, and IGF-1/IGF-2 ratio ruling out insulinoma, adrenal insufficiency, and GISTrelated paraneoplastic syndrome. Imaging studies, including PET and CT, showed no radiological evidence of recurrent GIST. Treatment with octreotide infusion resulted in minimal improvement, whereas daily corticosteroid therapy significantly alleviated the patient’s symptoms. The etiology of hypoglycemia remains elusive, with potential causes under consideration including Y-90 radioembolization-induced damage to glucagon-producing cells, immunotherapy-related adverse effects, or radiologically occult GIST. Insulin autoantibody testing is pending, and the case remains under active investigation, highlighting the diagnostic complexity of hypoglycemia in advanced GIST.

Discussion

Hypoglycemia in the context of GIST is a rare and poorly understood phenomenon. Potential mechanisms include paraneoplastic syndromes, such as non-islet cell tumor hypoglycemia (NICTH) mediated by IGF-2, or treatment-related effects, such as radiation-induced pancreatic or hepatic dysfunction. In this case, the absence of detectable IGF-2 abnormalities and negative imaging complicates the diagnosis. The lack of response to octreotide indicates that somatostatin receptor-mediated pathways may not be involved. The discontinuation of imatinib and prior Y-90 radioembolization further broadens the differential, as both could contribute to metabolic dysregulation.

Conclusions

This case illustrates the need for a systematic and multidisciplinary approach to evaluate hypoglycemia in patients with advanced GIST.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Immune-related adverse events (irAEs) associated with checkpoint inhibitors can involve virtually any organ system. Optic neuritis is a rare but potentially reversible toxicity, with limited reports in the literature.

Case Presentation

A 57-year-old male with Stage IV poorly-differentiated neuroendocrine carcinoma presented with progressive bilateral vision loss following a near-complete response to four cycles of atezolizumab, carboplatin, and etoposide chemotherapy, and one cycle of maintenance atezolizumab. Symptoms began in the right eye and progressed to the left over 12 days. Neurological and ophthalmological evaluations included brain and orbital MRI, autoimmune panels, and infectious workup, all of which were unrevealing. The clinical picture remained consistent with isolated, immunemediated optic neuritis.

Discussion

High-dose intravenous methylprednisolone was initiated, resulting in gradual improvement and partial visual recovery by day four. An oral prednisone taper was prescribed for continued treatment. This is the second reported case of isolated optic neuritis associated with PD-L1 inhibitor therapy and the second with negative imaging findings. The rarity of this irAE and the absence of radiographic abnormalities may delay diagnosis and treatment.

Conclusions

Checkpoint-inhibitor-induced optic neuritis should be considered in patients with visual symptoms on immunotherapy, even in the setting of negative imaging. Early recognition and corticosteroid therapy are critical in preserving visual function.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma most commonly arising in mucosal, nodal, or splenic tissues. While extranodal presentations are recognized, involvement of the sciatic foramen is exceedingly rare. We present a unique case of stage IV MZL with primary involvement of the left sciatic foramen, identified incidentally during urologic evaluation.

Case Presentation

A 74-year-old male patient was referred for hematologic evaluation after imaging revealed a left sciatic foraminal mass during work-up for elevated PSA. CT abdomen/pelvis revealed a 4.7 cm mass in the left sciatic foramen. Follow-up PET-CT confirmed hypermetabolic activity in the mass, with additional areas of uptake in the right ilium and pleural- pericardial regions. The patient was asymptomatic and denied B-symptoms. CT-guided biopsy of the sciatic mass revealed low-grade B-cell lymphoma. Flow cytometry showed a CD20-positive, CD5-negative, CD10-negative, lambda light chain–restricted population consistent with marginal zone lymphoma. Laboratory studies demonstrated iron deficiency anemia, with otherwise unremarkable counts and chemistries. He was started on monotherapy with rituximab for four cycles. He tolerated treatment well. Interval PET imaging in April 2025 showed stable disease in the sciatic foramen and mild improvement in pleural- pericardial uptake. He is planned to start obinutuzumab in the upcoming month.

Discussion

This case illustrates a rare anatomic presentation of MZL, likely representing primary sciatic foramen involvement. The presence of additional PETavid lesions complicates staging, raising consideration of stage I vs. III/IV disease. Biopsy was limited to the sciatic lesion, and no bone marrow sampling was performed. Given the patient’s excellent performance status, absence of symptoms, and low tumor burden, single-agent rituximab was chosen initially in accordance with NCCN guidelines.

Conclusions

Sciatic foramen involvement by MZL is an extremely rare occurrence and may mimic more common soft tissue or neurogenic tumors radiographically. This case underscores the importance of biopsy for diagnosis and the value of multidisciplinary care. In the veteran population, such incidental findings on imaging warrant comprehensive evaluation, particularly in atypical anatomical sites.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.

Background

Hypereosinophilic syndrome (HES) is a rare condition caused by an overproduction of eosinophils leading to tissue infiltration and end-organ damage. HES can infiltrate the heart and lead to rare but severe cases of eosinophilic endomyocarditis, potentially causing heart failure, restrictive cardiomyopathy, and thromboembolic events.

Case Presentation

A 53-year-old female presented for abdominal pain but was found to have significant leukocytosis and eosinophilia with an absolute eosinophil count of 15.50×109/L. Further imaging with cardiac MRI showed early nodular subendocardial enhancement suggestive of eosinophilic endomyocarditis. Bone marrow biopsy was negative for clonal disorders and gastric biopsy was negative for eosinophils and H. pylori. Treatment with high-dose prednisone caused reduction in eosinophils and repeat cardiac MRI showed significant improvement in endomyocarditis.

Discussion

HES is a rare condition characterized by persistently elevated eosinophilia that can cause end organ damage, mainly affecting the heart, lungs, skin and GI system. It can be caused by primary, secondary, or idiopathic mechanisms. Primary HES often involves genetic mutations, whereas secondary HES arises due to infections or malignancies. Idiopathic HES is mainly a diagnosis of exclusion. Workup includes bone marrow biopsies and molecular testing to help differentiate between different causes and guide treatment. Eosinophilic endomyocarditis (EM) is a rare and severe complication of HES caused by eosinophilic infiltration of the myocardium. It is characterized by myocardial inflammation, fibrosis, edema, arrhythmias and heart failure if left untreated. EM is a major cause of mortality and morbidity among patients with HES. Cardiac MRI is helpful for early detection but endomyocardial biopsy is the gold standard for definitive diagnosis. Early treatment with corticosteroids can significantly reduce eosinophilic infiltration and improve outcomes. Given the severity of this rare manifestation of HES, further research is needed to help improve diagnostic and treatment strategies for EM.

Conclusions

HES is a rare condition that can cause damage affecting multiple organs with one such complication being eosinophilic endomyocarditis, a condition known to increase mortality and morbidity in those with HES. Early but accurate diagnosis and timely intervention with corticosteroids is necessary for improving the overall outcomes of those affected with this.

Background

Genetic testing can reveal inherited or acquired genetic changes that can help with identifying diagnosis, treatment, prognosis, and risk of the malignancy. CDH1 is a gene that prevents cancer by controlling cell growth. Mutated CDH1 gene can lead to specific malignancies including gastric and breast cancer.

Case Presentation

42 year old female with past medical history of ovarian cysts presented to the VA Emergency Department for right sided abdominal pain and red colored stool. Further workup showed ileocolonic intussusception with stranding. She underwent a colonoscopy which showed 4 centimeter mass at the ileocecal valve. Biopsy was done which showed invasive adenocarcinoma. She underwent laparoscopic hemicolectomy and was referred to oncology. Referral to genetic testing was positive for CDH1 gene mutation. She was advised that CDH1 mutation has a high risk of developing gastric and breast cancer with recommendations including possible total gastrectomy and bilateral mastectomies. The patient however, decided to decline gastrectomy and mastectomy and instead decided to be followed by frequent EGDs and mammograms.

Discussion

CDH1 mutations are found in only 3.8% of colorectal signet ring cell cancers, with limited data of their presence in typical adenocarcinomas. This case underscores the value of genetic testing in all colorectal adenocarcinomas for its prognostic significance and potential impact on other cancer screenings. CDH1 mutations can lead to an aggressive type of gastric cancer called hereditary diffuse gastric cancer in 56-70% of patients with the mutation. CDH1 mutations also have a 37-55% of having breast cancer compared to the 12% in the general population and patients tend to present with lobular breast cancer. Patients with positive CDH1 mutation should have regular screenings or in some cases, prophylactic surgery.

Background

Genetic testing can reveal inherited or acquired genetic changes that can help with identifying diagnosis, treatment, prognosis, and risk of the malignancy. CDH1 is a gene that prevents cancer by controlling cell growth. Mutated CDH1 gene can lead to specific malignancies including gastric and breast cancer.

Case Presentation

42 year old female with past medical history of ovarian cysts presented to the VA Emergency Department for right sided abdominal pain and red colored stool. Further workup showed ileocolonic intussusception with stranding. She underwent a colonoscopy which showed 4 centimeter mass at the ileocecal valve. Biopsy was done which showed invasive adenocarcinoma. She underwent laparoscopic hemicolectomy and was referred to oncology. Referral to genetic testing was positive for CDH1 gene mutation. She was advised that CDH1 mutation has a high risk of developing gastric and breast cancer with recommendations including possible total gastrectomy and bilateral mastectomies. The patient however, decided to decline gastrectomy and mastectomy and instead decided to be followed by frequent EGDs and mammograms.

Discussion

CDH1 mutations are found in only 3.8% of colorectal signet ring cell cancers, with limited data of their presence in typical adenocarcinomas. This case underscores the value of genetic testing in all colorectal adenocarcinomas for its prognostic significance and potential impact on other cancer screenings. CDH1 mutations can lead to an aggressive type of gastric cancer called hereditary diffuse gastric cancer in 56-70% of patients with the mutation. CDH1 mutations also have a 37-55% of having breast cancer compared to the 12% in the general population and patients tend to present with lobular breast cancer. Patients with positive CDH1 mutation should have regular screenings or in some cases, prophylactic surgery.

Background

Genetic testing can reveal inherited or acquired genetic changes that can help with identifying diagnosis, treatment, prognosis, and risk of the malignancy. CDH1 is a gene that prevents cancer by controlling cell growth. Mutated CDH1 gene can lead to specific malignancies including gastric and breast cancer.

Case Presentation

42 year old female with past medical history of ovarian cysts presented to the VA Emergency Department for right sided abdominal pain and red colored stool. Further workup showed ileocolonic intussusception with stranding. She underwent a colonoscopy which showed 4 centimeter mass at the ileocecal valve. Biopsy was done which showed invasive adenocarcinoma. She underwent laparoscopic hemicolectomy and was referred to oncology. Referral to genetic testing was positive for CDH1 gene mutation. She was advised that CDH1 mutation has a high risk of developing gastric and breast cancer with recommendations including possible total gastrectomy and bilateral mastectomies. The patient however, decided to decline gastrectomy and mastectomy and instead decided to be followed by frequent EGDs and mammograms.

Discussion

CDH1 mutations are found in only 3.8% of colorectal signet ring cell cancers, with limited data of their presence in typical adenocarcinomas. This case underscores the value of genetic testing in all colorectal adenocarcinomas for its prognostic significance and potential impact on other cancer screenings. CDH1 mutations can lead to an aggressive type of gastric cancer called hereditary diffuse gastric cancer in 56-70% of patients with the mutation. CDH1 mutations also have a 37-55% of having breast cancer compared to the 12% in the general population and patients tend to present with lobular breast cancer. Patients with positive CDH1 mutation should have regular screenings or in some cases, prophylactic surgery.

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.

Case Presentation

A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.

Discussion

Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.

Case Presentation

A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.

Discussion

Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematologic disorder that includes a combination of thrombocytopenia, microangiopathic hemolytic anemia, and neuropsychiatric symptoms. The pathogenesis of TTP is due to a deficiency of ADAMTS13. While early initiation of plasma exchange is vital for managing TTP, differentiating TTP from disseminated intravascular coagulation, hemolytic uremic syndrome, and heparin-induced thrombocytopenia is challenging. Standard of care includes plasma exchange and immunosuppressive agents. Relapse occurs in 36% of patients, and mortality rates range from 10% to 20%. Caplacizumab was approved in 2019 for the treatment of adults with acquired TTP in conjunction with the above therapies. Here we report a case of a 52- year-old patient treated with caplacizumab for TTP at our institution.

Case Presentation

A 52-year-old Jehovah’s Witness female with no prior hematologic history presented with one-day history of nausea and vomiting. While the patient did not initially present with neurologic changes, she did later become acutely confused, endorsing tactile hallucinations. Physical exam was notable for scattered ecchymoses on the upper extremities. Labs were notable for thrombocytopenia with a platelet count of 30,000, hemoglobin 13.6, and creatinine 1.5. There was evidence of hemolysis with elevated LDH, fibrinogen, undetectable haptoglobin, and schistocytes on peripheral smear. Her PLASMIC score on admission was 6. ADAMTS13 level was low at 0.5. The patient was initially on plasma exchange therapy and IV steroids, but with her degree of multiorgan dysfunction, treatment was escalated to caplacizumab and weekly rituximab. Platelet counts started to improve on hospital day four, and at the time of discharge, symptoms improved. Patient’s mental status returned to baseline and labs showed normalization of platelet count, hemoglobin, with improvement in kidney function.

Discussion

Early diagnosis and treatment of TTP is crucial for improving outcomes for patients. Here we show that treatment with caplacizumab is an effective adjunct therapy to steroids and plasmapheresis in patients with severe disease and multiorgan dysfuncition and is effective in rapidly improving hematologic abnormalities. While our patient was ultimately accepting of plasma exchange, caplacizumab could be considered as an off-label therapy in patients who are Jehovah’s witness patients and refuse treatment with plasma.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

GATA3 is a zinc finger transcription factor most commonly used as an immunohistochemical marker in breast and urothelial carcinomas, though it has also been detected—albeit infrequently—in other malignancies. While GATA3 expression is well established in esophageal squamous cell carcinoma, it is rarely documented in esophageal adenocarcinoma. We present a unique case of widely metastatic, strongly GATA3-positive esophageal adenocarcinoma.

Case Presentation

A 59-year-old male smoker with gastroesophageal reflux disease and a history of alcohol use disorder presented with progressive right hip pain following a fall. Imaging revealed multiple lytic bone lesions and a soft tissue mass near the right acetabulum. PET-CT demonstrated widespread osseous metastases and FDG-avid uptake in the distal esophagus and perigastric lymph nodes. Laboratory findings included a PSA of 14. Biopsy of the right pubic ramus revealed adenocarcinoma positive for GATA3, CK7, CK20 (patchy), CK40, and P63, and negative for PSA. Given the unexpected GATA3 positivity, the differential diagnosis included primary urothelial cancer. However, cystoscopy and urine cytology were unremarkable. EGD revealed Barrett’s esophagus without a discrete mass. Biopsy of the distal esophagus confirmed poorly differentiated adenocarcinoma with underlying dysplasia. Molecular profiling showed HER2-negative, microsatellite stable (MSS) disease with PD-L1 expression of 10%. Due to an ECOG performance status ≥3 and extensive metastatic burden, the patient was not a candidate for systemic therapy and was transitioned to hospice care.

Discussion

A large tissue microarray study of over 16,000 tumors found weak GATA3 expression in only 2.4% of esophageal adenocarcinomas, with strong or diffuse positivity virtually undocumented. In this case, the unusual immunoprofile initially raised concern for a primary urothelial tumor, but endoscopic biopsy confirmed an esophageal origin. Aberrant GATA3 expression in poorly differentiated gastrointestinal tumors may complicate diagnosis and has been associated with worse prognosis. Awareness of such atypical patterns is critical for accurate tumor classification and appropriate management in metastatic disease.

Conclusions

This case highlights a rare presentation of GATA3-positive esophageal adenocarcinoma. Further reporting may improve diagnostic accuracy and inform future therapeutic strategies for this unique subset of tumors.

Background

Choroidal malignant melanoma is a relatively rare condition, yet it remains the most common primary intraocular malignancy in adults, affecting approximately 5 individuals per million each year in the United States. Associated risk factors include fair skin, light-colored eyes, ocular melanocytosis, and BAP1 genetic mutations. While 13% of patients presenting with choroidal melanoma are asymptomatic, some symptoms can include photopsia, floaters, blurred vision, and progressive visual field loss.

Case Presentation

We present a case of choroidal melanoma in a 57-year-old male with a past medical history of hypertension, hyperlipidemia, major depressive disorder, and alcohol use disorder. This patient presented to the clinic following a detoxification admission, reporting one week of progressive vision loss in the left eye. Upon initial physical examination, the patient exhibited left superior quadrantanopia, with a visual acuity of 20/40 measured in the left eye. Initial imaging with CT head identified an intraocular hyperdensity within the left globe, raising concerns for potential retinal detachment. Urgent ophthalmologic evaluation revealed an afferent pupillary defect and a large choroidal lesion adjacent to the optic nerve head. Ultrasonography showed a low internal reflectivity mass (5.36 mm by 9.05 mm), and a subsequent dilated fundus examination confirmed a classic dome-shaped choroidal melanoma (11.5 mm by 16.5 mm). Gene expression profiling demonstrated a class 1b uveal melanoma with PRAME positivity and mutations in GNAQ and SF3B1. Comprehensive staging scans were negative for metastatic disease. The patient received four treatment sessions of proton beam therapy, which resulted in rapid improvements in his visual fields. For long-term management, he was scheduled for close ophthalmologic follow-up and regular imaging of the chest and abdomen every six months to monitor for recurrence.

Conclusions

This case highlights the challenges of diagnosing choroidal melanoma in the primary care setting and the importance of multidisciplinary involvement, multimodal imaging, and gene expression profiling in facilitating early diagnosis and treatment.

Background

Choroidal malignant melanoma is a relatively rare condition, yet it remains the most common primary intraocular malignancy in adults, affecting approximately 5 individuals per million each year in the United States. Associated risk factors include fair skin, light-colored eyes, ocular melanocytosis, and BAP1 genetic mutations. While 13% of patients presenting with choroidal melanoma are asymptomatic, some symptoms can include photopsia, floaters, blurred vision, and progressive visual field loss.

Case Presentation

We present a case of choroidal melanoma in a 57-year-old male with a past medical history of hypertension, hyperlipidemia, major depressive disorder, and alcohol use disorder. This patient presented to the clinic following a detoxification admission, reporting one week of progressive vision loss in the left eye. Upon initial physical examination, the patient exhibited left superior quadrantanopia, with a visual acuity of 20/40 measured in the left eye. Initial imaging with CT head identified an intraocular hyperdensity within the left globe, raising concerns for potential retinal detachment. Urgent ophthalmologic evaluation revealed an afferent pupillary defect and a large choroidal lesion adjacent to the optic nerve head. Ultrasonography showed a low internal reflectivity mass (5.36 mm by 9.05 mm), and a subsequent dilated fundus examination confirmed a classic dome-shaped choroidal melanoma (11.5 mm by 16.5 mm). Gene expression profiling demonstrated a class 1b uveal melanoma with PRAME positivity and mutations in GNAQ and SF3B1. Comprehensive staging scans were negative for metastatic disease. The patient received four treatment sessions of proton beam therapy, which resulted in rapid improvements in his visual fields. For long-term management, he was scheduled for close ophthalmologic follow-up and regular imaging of the chest and abdomen every six months to monitor for recurrence.

Conclusions

This case highlights the challenges of diagnosing choroidal melanoma in the primary care setting and the importance of multidisciplinary involvement, multimodal imaging, and gene expression profiling in facilitating early diagnosis and treatment.

Background

Choroidal malignant melanoma is a relatively rare condition, yet it remains the most common primary intraocular malignancy in adults, affecting approximately 5 individuals per million each year in the United States. Associated risk factors include fair skin, light-colored eyes, ocular melanocytosis, and BAP1 genetic mutations. While 13% of patients presenting with choroidal melanoma are asymptomatic, some symptoms can include photopsia, floaters, blurred vision, and progressive visual field loss.

Case Presentation

We present a case of choroidal melanoma in a 57-year-old male with a past medical history of hypertension, hyperlipidemia, major depressive disorder, and alcohol use disorder. This patient presented to the clinic following a detoxification admission, reporting one week of progressive vision loss in the left eye. Upon initial physical examination, the patient exhibited left superior quadrantanopia, with a visual acuity of 20/40 measured in the left eye. Initial imaging with CT head identified an intraocular hyperdensity within the left globe, raising concerns for potential retinal detachment. Urgent ophthalmologic evaluation revealed an afferent pupillary defect and a large choroidal lesion adjacent to the optic nerve head. Ultrasonography showed a low internal reflectivity mass (5.36 mm by 9.05 mm), and a subsequent dilated fundus examination confirmed a classic dome-shaped choroidal melanoma (11.5 mm by 16.5 mm). Gene expression profiling demonstrated a class 1b uveal melanoma with PRAME positivity and mutations in GNAQ and SF3B1. Comprehensive staging scans were negative for metastatic disease. The patient received four treatment sessions of proton beam therapy, which resulted in rapid improvements in his visual fields. For long-term management, he was scheduled for close ophthalmologic follow-up and regular imaging of the chest and abdomen every six months to monitor for recurrence.

Conclusions

This case highlights the challenges of diagnosing choroidal melanoma in the primary care setting and the importance of multidisciplinary involvement, multimodal imaging, and gene expression profiling in facilitating early diagnosis and treatment.

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?