Conference Coverage

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.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Immune checkpoint inhibitors (ICI) have changed the landscape of cancer therapy. Pembrolizumab is an ICI which targets programmed cell death protein-1 on T-cells and acts to release inhibition of the T-cell antitumor response. Pembrolizumab is approved for the treatment of multiple malignancies. However, ICI therapy may precipitate immune-related adverse events (IRAEs). We describe a unique presentation of irAE-cardiotoxicity.

Case Discussion

A 70-year-old female with a history of uterine cancer previously treated with pembrolizumab (discontinued in January) presented to the emergency department with acute onset nausea and vomiting. On arrival, she was afebrile, tachycardic, normotensive, and saturated well in room air. Labs were notable for troponin of 20, normal TSH, elevated proBNP, ESR and CRP. EKG revealed atrial fibrillation with rapid ventricular response and subtle ST changes in leads II, aVF, V4-V6. She was started on diltiazem infusion for rate control and was subsequently transitioned to oral amiodarone. Given the concern for pericarditis, NSAIDs were initiated. Transthoracic echocardiogram was notable for an ejection fraction of 58% with moderate circumferential pericardial effusion without tamponade. Given her recent ICI exposure and evolving clinical course, she was diagnosed with pembrolizumab- induced pericarditis with associated atrial fibrillation and pericardial effusion. High-dose corticosteroids and colchicine were initiated for stabilization and symptomatic improvement.

Discussion

IRAEs usually occur within 3 months of therapy but may develop later. They are classified as low-grade (1-2), high-grade (3-4), or lethal (5). Anti- PD1 therapy is frequently associated with minor IRAEs, which develop in ~70% of patients; dermatologic IRAEs are most common. Major IRAEs develop in 10-15% of patients, and lethal IRAEs may develop in up to 3%. Cardiac IRAEs are infrequent but significant. Presentation is variable and may involve the myocardium, pericardium, or conductive system. In the case of pericardial disease, high-dose IV methylprednisolone with oral steroid taper should be considered. Re-challenge with ICI therapy should only be considered if clinically stable and pericarditis or myocarditis are excluded.

Conclusions

Our patient illustrates a rare but significant IRAE associated with ICI with improvement following immunosuppressive and rate-control therapy.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Sickle cell disease (SCD) patients often present with pain and fever, commonly attributed to vaso-occlusive crises (VOC), which can delay the diagnosis of other conditions. This highlights the need for reassessment and bias-aware clinical reasoning.

Case Presentation

A 27-year-old male with SCD, prior hip replacement, and cholecystectomy presented with whole-body pain. Labs supported VOC with anemia, elevated LDH, and reticulocytosis. Despite RUQ tenderness and a positive Murphy sign, the ultrasound was unremarkable, and he was admitted for VOC management. Persistent fever >48 hours prompted further evaluation with MRCP, revealing choledocholithiasis with common bile duct and mild biliary dilatation; later, his pain and fever resolved by ERCP, and he was discharged. However, he returned the following day with whole-body and right upper quadrant pain; lab tests showed normal hemoglobin, LDH, and reticulocyte levels, indicating no active sickling. On follow-ups, the patient started to have fever episodes again. Subsequent fevers prompted a CT scan, revealing pulmonary embolism involving the right interlobar pulmonary artery extending into the segmental and subsegmental vessels and right lower lobe pneumonia. He denied any cough or shortness of breath. Treatment with Eliquis for the embolism and antibiotics for hospital-acquired pneumonia resolved the fever and leukocytosis, but the patient persistently requested high-dose opioids despite normal sickling labs.

Discussion

This case highlights the need for diagnostic flexibility in SCD, as anchoring bias may cause clinicians to overlook other life-threatening conditions when VOC is suspected. The patient’s symptoms, initially suggestive of VOC, were later linked to choledocholithiasis, pulmonary embolism, and pneumonia, highlighting how overlapping complications can be misattributed to a single episode. The delayed diagnosis reflects cognitive and systemic factors, with few reports emphasizing the diagnostic delays when multiple SCD-related complications occur together. The stigma surrounding opioid use may also hinder timely care escalation. This case highlights the need for structured reassessment, red-flag criteria, and multidisciplinary collaboration to improve diagnostic accuracy and prevent fatal delays in complex SCD presentations.

Conclusions

This case emphasizes reassessing persistent symptoms in SCD, avoiding anchoring bias, and recognizing red flags. Multidisciplinary evaluation and bias-aware practices are key to accurate, timely care.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.