AVAHO

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

Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.

Case Presentation

A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.

Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.

Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.

Discussion

While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.

Conclusions

Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.

Background

Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.

Case Presentation

A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.

Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.

Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.

Discussion

While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.

Conclusions

Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.

Background

Whereas light chain (AL) amyloid is the most common cause of amyloidosis, Apolipoprotein A-IV (AApoAIV) amyloid is rare. Here we describe the first case of renal amyloidosis with pathology demonstrating concurrent deposition of AL and AApoAIV amyloid.

Case Presentation

A 79-year-old man presented with bilateral leg swelling and was diagnosed with nephrotic syndrome with preserved renal function. Serum protein electrophoresis and immunofixation showed no measurable monoclonal protein. Serum lambda free light chains were elevated at 97.72 mg/L, and kappa:lambda ratio was 0.22. Pathology from renal biopsy showed focal deposits of Congo red staining. Liquid chromatography tandem mass spectrometry identified both fibrillogenic ApoIV signal sequence peptides and a peptide profile consistent with AL amyloid deposition.

Further testing showed mild Bence Jones proteinuria, mildly elevated beta-2 microglobulin, elevated cardiac troponin T, normal NT-pro-B-type natriuretic peptide, and normal Factor X activity. Echocardiogram and FDG PET CT were unremarkable. Bone marrow biopsy demonstrated a lambda-restricted monotypic plasma cell population comprising 10% of plasma cells by immunohistochemistry. Although the Congo red stain was indeterminate, IGH::CCND1 fusion was detected by FISH.

Treatment was initiated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone. Serum lambda light chains normalized after one cycle. Urine protein:creatinine ratio improved from 7.0 to 3.0 by the end of cycle 3. The patient will soon complete cycle 4 and undergo reassessment.

Discussion

While there are rare reports of AApoAIV renal amyloidosis and more prevalent cases of AL renal amyloidosis, the presence of both types of amyloid in the same patient has not been previously reported. AApoAIV renal amyloidosis has no established treatment and tends to present with rising serum creatinine as opposed to proteinuria. Given our patient’s clinical presentation with nephrotic syndrome and current light chain response to treatment, AL amyloidosis may be predominantly driving the disease.

Conclusions

Given the rarity of renal amyloidosis involving both AL and AApoAIV amyloid, the clinical course and optimal treatments are not established. The cumulative knowledge gained from individual case studies can serve as a basis for ongoing investigation and management of similar cases in the future.

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?

Background

Vitamin B12 deficiency is a well-recognized cause of megaloblastic anemia. In severe cases, it can lead to neuropsychiatric symptoms, hemolytic anemia, and pancytopenia.

Case Presentation

A 60-year-old male presented due to multiple falls and confusion. On presentation, he was markedly altered and unable to provide a history. His spouse reported a one-day history of incoordination and confusion. Physical examination revealed an ill-appearing male who was unable to follow commands with non-purposeful movements of all extremities. Initial labs showed a WBC 0.5 x103/μL, Hgb 3.6 g/dL, MCV 118.8 fL, platelets 7 x 103/μL, lymphocytes 50%, atypical lymphocytes 2%, and total bilirubin of 2.1 mg/dL (direct bilirubin 0.8 mg/dL). Further evaluation showed a reticulocyte count of 7.8 x109/L, reticulocyte 1%, and reticulocyte index of 0.7. Iron studies were unremarkable. Lactate dehydrogenase was elevated at 796 U/L and haptoglobin was undetectably low (< 20 mg/dL). Peripheral smear showed macrocytic anemia, anisopoikilocytosis, leukopenia with hypersegmented neutrophils, and thrombocytopenia; no schistocytes were noted. Additional labs showed folate of 3.8 ng/mL and an undetectably low vitamin B12 level (< 159 pg/mL). Anti-parietal cell and intrinsic factor blocking antibodies were negative. Infectious workups and serum protein electrophoresis were negative. The patient was diagnosed with severe vitamin B12 deficiency resulting in pancytopenia, hemolytic anemia secondary to intramedullary hemolysis, and neuropsychiatric changes. He was started on daily intramuscular (IM) cyanocobalamin (1000 mcg) and supportive transfusions. Over the hospitalization, his mentation returned to baseline and his cell counts stabilized.

Discussion

Vitamin B12 is an important co-factor needed for the synthesis of DNA and myelin. Vitamin B12 deficiency most commonly presents with megaloblastic anemia but neuropsychiatric manifestations can occur in severe cases. Pancytopenia occurs in ~5% of patients with B12 deficiency, whereas hemolytic anemia occurs in only ~1.5% of patients. Hemolytic anemia secondary to B12 deficiency is thought to be due to ineffective erythropoiesis causing intramedullary hemolysis. Prompt diagnosis and B12 supplementation can lead to rapid clinical recovery.

Conclusions

This case highlights the importance of considering vitamin B12 deficiency in patients with unexplained pancytopenia, hemolytic anemia, and neuropsychiatric symptoms. Early diagnosis and treatment can lead to significant and rapid clinical improvement.

Background

Vitamin B12 deficiency is a well-recognized cause of megaloblastic anemia. In severe cases, it can lead to neuropsychiatric symptoms, hemolytic anemia, and pancytopenia.

Case Presentation

A 60-year-old male presented due to multiple falls and confusion. On presentation, he was markedly altered and unable to provide a history. His spouse reported a one-day history of incoordination and confusion. Physical examination revealed an ill-appearing male who was unable to follow commands with non-purposeful movements of all extremities. Initial labs showed a WBC 0.5 x103/μL, Hgb 3.6 g/dL, MCV 118.8 fL, platelets 7 x 103/μL, lymphocytes 50%, atypical lymphocytes 2%, and total bilirubin of 2.1 mg/dL (direct bilirubin 0.8 mg/dL). Further evaluation showed a reticulocyte count of 7.8 x109/L, reticulocyte 1%, and reticulocyte index of 0.7. Iron studies were unremarkable. Lactate dehydrogenase was elevated at 796 U/L and haptoglobin was undetectably low (< 20 mg/dL). Peripheral smear showed macrocytic anemia, anisopoikilocytosis, leukopenia with hypersegmented neutrophils, and thrombocytopenia; no schistocytes were noted. Additional labs showed folate of 3.8 ng/mL and an undetectably low vitamin B12 level (< 159 pg/mL). Anti-parietal cell and intrinsic factor blocking antibodies were negative. Infectious workups and serum protein electrophoresis were negative. The patient was diagnosed with severe vitamin B12 deficiency resulting in pancytopenia, hemolytic anemia secondary to intramedullary hemolysis, and neuropsychiatric changes. He was started on daily intramuscular (IM) cyanocobalamin (1000 mcg) and supportive transfusions. Over the hospitalization, his mentation returned to baseline and his cell counts stabilized.

Discussion

Vitamin B12 is an important co-factor needed for the synthesis of DNA and myelin. Vitamin B12 deficiency most commonly presents with megaloblastic anemia but neuropsychiatric manifestations can occur in severe cases. Pancytopenia occurs in ~5% of patients with B12 deficiency, whereas hemolytic anemia occurs in only ~1.5% of patients. Hemolytic anemia secondary to B12 deficiency is thought to be due to ineffective erythropoiesis causing intramedullary hemolysis. Prompt diagnosis and B12 supplementation can lead to rapid clinical recovery.

Conclusions

This case highlights the importance of considering vitamin B12 deficiency in patients with unexplained pancytopenia, hemolytic anemia, and neuropsychiatric symptoms. Early diagnosis and treatment can lead to significant and rapid clinical improvement.

Background

Vitamin B12 deficiency is a well-recognized cause of megaloblastic anemia. In severe cases, it can lead to neuropsychiatric symptoms, hemolytic anemia, and pancytopenia.

Case Presentation

A 60-year-old male presented due to multiple falls and confusion. On presentation, he was markedly altered and unable to provide a history. His spouse reported a one-day history of incoordination and confusion. Physical examination revealed an ill-appearing male who was unable to follow commands with non-purposeful movements of all extremities. Initial labs showed a WBC 0.5 x103/μL, Hgb 3.6 g/dL, MCV 118.8 fL, platelets 7 x 103/μL, lymphocytes 50%, atypical lymphocytes 2%, and total bilirubin of 2.1 mg/dL (direct bilirubin 0.8 mg/dL). Further evaluation showed a reticulocyte count of 7.8 x109/L, reticulocyte 1%, and reticulocyte index of 0.7. Iron studies were unremarkable. Lactate dehydrogenase was elevated at 796 U/L and haptoglobin was undetectably low (< 20 mg/dL). Peripheral smear showed macrocytic anemia, anisopoikilocytosis, leukopenia with hypersegmented neutrophils, and thrombocytopenia; no schistocytes were noted. Additional labs showed folate of 3.8 ng/mL and an undetectably low vitamin B12 level (< 159 pg/mL). Anti-parietal cell and intrinsic factor blocking antibodies were negative. Infectious workups and serum protein electrophoresis were negative. The patient was diagnosed with severe vitamin B12 deficiency resulting in pancytopenia, hemolytic anemia secondary to intramedullary hemolysis, and neuropsychiatric changes. He was started on daily intramuscular (IM) cyanocobalamin (1000 mcg) and supportive transfusions. Over the hospitalization, his mentation returned to baseline and his cell counts stabilized.

Discussion

Vitamin B12 is an important co-factor needed for the synthesis of DNA and myelin. Vitamin B12 deficiency most commonly presents with megaloblastic anemia but neuropsychiatric manifestations can occur in severe cases. Pancytopenia occurs in ~5% of patients with B12 deficiency, whereas hemolytic anemia occurs in only ~1.5% of patients. Hemolytic anemia secondary to B12 deficiency is thought to be due to ineffective erythropoiesis causing intramedullary hemolysis. Prompt diagnosis and B12 supplementation can lead to rapid clinical recovery.

Conclusions

This case highlights the importance of considering vitamin B12 deficiency in patients with unexplained pancytopenia, hemolytic anemia, and neuropsychiatric symptoms. Early diagnosis and treatment can lead to significant and rapid clinical improvement.

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.