United States

Factors 8 and 9 play pivotal roles in the activation of factor 10 in the coagulation cascade. In acquired factor 8 inhibitor, IgG autoantibodies bind to factor 8 molecules causing a functional factor 8 deficiency. Incidence is exceedingly rare at one to four per million per year. We discuss a case of severe acquired factor 8 defiency and discuss the diagnostic and treatment approach.

2023 AMA Research Challenge

Diagnostic and Therapeutic Complexities in a Case of Severe Acquired Factor 8 
Deficiency

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Background
This case presented with symptomatic anemia shortly after being diagnosed in NOV/2021 with Invasive Ductal Carcinoma in the left breast T4N2M0. She had chest pain, dry cough, epigastric pain, nausea and generalized fatiguability 3 weeks prior, no past medical history, but significant positive family history for non-Hodgkin Lymphoma. However, finding compatible blood units was very challenging and transfusion dependency was developed. The main approach is to reach clinical stability when she can receive the first cycle of neoadjuvant chemotherapy.

Methods
A complete blood profile, hemolysis indicators, Hb electrophoresis, CT scan of the abdomen was required to evaluate the case and bone marrow aspiration, biopsy, and immunohistochemistry study. Numerous PRBC units were given to support the patient under close monitoring with oral prednisolone, cyclophosphamide, and IVIg.
Result
She shows a hemolytic pattern with hemoglobin level at 6.3g/dl, with mild neutrophilia, normal platelets, reticulocytosis, indirect hyperbilirubinemia, positive direct Coomb’s test and high serum ferritin at 1045ng/L . However, the haptoglobin was not detected, MCV was normal, LDH level was not elevated at 170 U/L, normal vitamin B12, liver enzymes, urea and electrolytes and uric acid,. Her blood group was A+, the HB electrophoresis showed HbA 97.5%, HbA2 2.5% and CT scan of abdomen revealed mild hepatosplenomegaly. The peripheral blood film shows Anisocytosis, neutrophilia and normal platelet, and bone marrow biopsy showed no malignant infiltration. An immunohistochemistry study shows that the malignant cells are positive for CK (Creatine kinase) and Mammaglobin while they are negative for LCA, CD20, CD3 and GCDFP15.

Conclusion 
Autoimmune hemolytic anemia (AIHA) is recognized relatively rare with solid tumors as a paraneoplastic syndrome. However, in this case due to her family history, lymphoma must be excluded by bone marrow biopsy and immunohistochemistry study. Patient did respond well to prednisolone nevertheless complicated by diabetes mellitus and gouty arthritis and received numerous units of packed red blood cells, her anemia was corrected and patient was fit to

A case report of autoimmune hemolytic anemia in a newly diagnosed patient with breast cancer Challenging transfusion dependency that interferes with neoadjuvant chemotherapy

We present a patient with antiphospholipid syndrome and thrombocytopenia that was found to have a rare mutation in the Vitamin K epoxide reductase complex subunit 1 which altered his response to Warfarin therapy. The patient had experienced multiple prior thrombolic events, however his low platelet count put him in danger of having a severe bleeding event. We describe below how we found a balance in managing both his clotting and bleeding risks.

Management of Recurrent Arterial Clots in Antiphospholipid Syndrome with Thrombocytopenia and Warfarin Resistant Gene

Background
Immune thrombocytopenia (ITP) is an isolated autoimmune condition most often heralded by viral infections such as HIV, Hepatitis C, and H. pylori. Few cases of documented ITP with influenza vaccinations and many cases with COVID-19 vaccines. However, reported cases of concomitant vaccine administration with ITP are not only rare but rather make it difficult to find the culprit vaccine. 

Case Presentation
A 92-year-old male with history of history of prostate cancer in remission, hyperlipidemia, & hypertension admitted for a fall. Patient had no recollection of his history. Vitals showed a hemodynamically stable patient with physical exam positive for generalized petechiae with concomitant ecchymoses all over his body. CBC showed platelets (PLTs) < 10,000. Imaging was negative. He was on chronic medications including simvastatin, losartan, and nifedipine. Immunization records indicated inactivated influenza and concomitant covid-19 Pfizer vaccination 1 week prior to admission. Investigations showed no history of thrombocytopenia, no recent hospital admission(s), no recent heparin or other antiplatelet/anticoagulant usage, no new medications, and no recent illnesses. Outpatient CBC showed PLT count of 266,000 and prior to 1 year ago showed a CBC with PLT count of 322,000. Blood smear showed normocytic, normochromic anemia with polychromasia, marked thrombocytopenia with occasional megakaryocyte, and no evidence of schistocytes, dysplasia, and or blast cells. Liver enzymes, acute hepatitis screen, immunoglobulins, & HIV viral panel were all negative including echo. Diagnosis of ITP was confirmed while ruling out other causes leading to eventual culprit being concomitant dual vaccination 1 week prior to patient presentation. In agreement with hematologist, patient was started on dexamethasone 40 mg daily and supportive care. 

Discussion

Overall, there are total 239 out of 482 cases of ITP with the Pfizer-BioNtech mRNA covid-19 vaccinations and 1 case of ITP with influenza quadrivalent FluBlok vaccination reported to the vaccine adverse reporting system (VAERS) to the Center for Diseases Prevention. Our patient showed improvement in his PLTs and was discharged, but quickly returned with refractory ITP to steroids further requiring intravenous immunoglobulin administration and induction with monoclonal antibody rituximab. In another systematic review of 77 patients showed de novo ITP related to covid-19 vaccination treated as traditional ITP. Despite safety and efficacy of these vaccines, healthcare personnel should self-educate about complications of vaccine related complications to further understand the treatment and management of such fatal complications. Furthermore, data needs to be collected to establish this cause-effect relationship so that the CDC can develop guidelines for safe co-administration.

Influenza & COVID-19 Vaccine Associated Severe Immune Thrombocytopenia

Chronic diarrhoea is not an uncommon presentation in a busy gastroenterology practice, however, it proves to be interesting and challenging to make a correct diagnosis. Some of the common causes of chronic diarrhoea include inflammatory bowel disease, irritable bowel syndrome, food allergies/ sensitivities, and infections (parasitic or tuberculosis), especially in tropical countries. Rare causes of chronic diarrhoea can include infiltrative disorders of the GI system including eosinophilic enteritis, microscopic colitis, and hemato-lymphoid malignancies. [1] Systemic amyloidosis can rarely present as chronic persistent diarrhoea due to GI infiltration. In this report, we describe a 72-year-old man presenting to the gastroenterology OPD with chronic diarrhoea and significant weight loss. He underwent a detailed evaluation for the causes of chronic diarrhoea. Duodenal biopsy showed light chain amyloid deposits, which led to the diagnosis of AL (light chain) Amyloidosis. Upon further evaluation for the source of amyloidosis; a PET CT followed by an excision biopsy of the lymph node revealed low-grade Non-Hodgkins lymphoma. Despite infiltrative disorders being a rare cause of chronic diarrhoea, care should be taken to thoroughly investigate for them when common etiologies for this disease are ruled out.

Key Words: Chronic diarrhoea; amyloidosis, NHL

Chronic diarrhoea as the presenting symptom in systemic AL Amyloidosis secondary to Non-Hodgkins Lymphoma

Background 
Radiation therapy (RT) serves as the mainstay adjuvant therapy in patients that underwent breast-conserving surgery for the management of breast cancer. Radiation induced rib fracture is a rare complication of radiotherapy. 


Case Presentation 
A 57-year-old African American female presented to the hospital after an abnormal screening mammogram demonstrated left breast calcifications. A left breast core biopsy revealed an intermediate- to high- grade ductal carcinoma in situ. The mass was excised. On immunohistochemical receptor assay, the mass was found to be estrogen receptor (+) and progesterone receptor (+). The patient was counselled on the initiation of adjuvant radiotherapy as part of the treatment regimen. 

Six months after her radiotherapy, the patient presented with a month-long discomfort on the left lower quadrant of her left breast, which aggravated with movement, despite the absence of trauma or falls. An X-ray demonstrated a subtle fracture of the tip of the left 10th rib and the lateral aspect of the left 7th rib, and the patient was treated conservatively. 

A PET-CT scan a month later showed a minimally displaced fracture of the left anterolateral 7th rib. The previously noted subtle fracture on the 10th rib was not appreciated on this examination. The patient returned to the clinic reporting a decreased pain intensity. A month later, the patient no longer had chest pain or discomfort and was informed that her subtle fractures have healed. 


Discussion 
Radiation-induced rib fractures (RIRF) refer to the occurrence of rib fractures after radiotherapy to the region close to a rib or within a path of a rib. They are considered pathological fractures, as they happen in underlying abnormal bone affected by radiation therapy. 

RIRFs are rare especially after hypofractionated stereotactic body radiation therapy (SBRT). It was reported that the incidence of RIRF with whole breast dose <50 Gy was 1.5% and >50 Gy was 5.3%. High-dose volume and the maximum dose have a direct relationship with RIRF. The toxic effects of radiation reduce osteoblast function and therefore, decreases bone matrix production leading to pathological fractures. The bones within the radiation portal are weakened, particularly if the primary irradiated tumor is close to the chest wall.

These patients may be asymptomatic or symptomatic and present with chest discomfort or pain after a few months of radiation. These symptoms usually resolve conservatively; therefore, a follow up of the patient and imaging should be considered.

Radiation-Induced Rib Fracture Post Breast Cancer Radiotherapy: A Case Report

Background
Intravascular large B cell lymphoma (IVLBCL) is difficult to diagnose and is exceedingly rare with an incidence of less than 1 in 1,000,000. Known as a great imitator, symptoms can include anything from fever, sensory and motor deficits, vertigo, vision loss, poor circumscribed violaceous plaques, or any variety of organ-specific symptoms. Diagnostic uncertainty and late presentation certainly play a role in the poor prognosis of patients diagnosed with IVLBCL, particularly in those with CNS involvement. 
Case Presentation
We describe a case of IVLBCL in a 56-year-old male which was identified after recurrent strokes. Symptoms included vertigo, hearing loss and tinnitus in the right ear, emesis, diaphoresis, and right facial paresthesia. Vasculitis, hypercoagulability, and cardiology workup for thromboembolism including echocardiogram and Holter test was negative. Despite these negative results, he continued to present with worsening symptoms and MRIs continued to demonstrate new, diffuse cerebral infarcts. Right partial nephrectomy was performed after the patient was stabilized due to a CT scan revealing a right renal mass. Pathology demonstrated renal oncocytoma and IVLBCL cells that were CD20+, PAX5+, CD10 trace+, BCL-6+, BCL-2+, MUM-1+, and negative for BCL-1 and CD34. Ki-67 staining was 100%. Chemotherapy was initiated with R-HyperCVAD (4 odd cycles included high doses of cyclophosphamide, vincristine, doxorubicin, and dexamethasone while 4 even cycles had high doses of methotrexate and cytarabine). Rituximab and two doses of intrathecal chemotherapy, one dose each of methotrexate and cytarabine, were utilized in both cycles. The patient achieved complete remission after termination of treatment and has remained in remission for 5 years after diagnosis.
Discussion
This case represents the first known report of R-HyperCVAD with intrathecal methotrexate and cytarabine for the treatment of IVLBCL with neurologic symptoms. R-HyperCVAD with intrathecal methotrexate has previously been described to achieve complete remission in IVLBCL for at least 2 years, but that case demonstrated no neurological symptoms with only a T2-hyperdense pontine lesion. R-CHOP is largely considered the treatment of choice in IVLBCL, however low doses of chemotherapy in this regimen do not pass through the blood brain barrier. R-HyperCVAD, on the other hand, provides ample CNS penetration that led to its use in this case due to the recurrent stroke symptoms. Our case demonstrates resolution of IVLBCL and its associated CNS symptoms for 5 years after diagnosis following treatment with R-HyperCVAD combined with intrathecal methotrexate and cytarabine. 


Intravascular Large B-Cell Lymphoma Masquerading as Stroke Successfully Treated with R-Hyper-CVAD

Background
Acute myeloid leukemia (AML) is the most common type of leukemia in adults, with a global incidence of about 120,000 cases annually. The incidence has surged by 87% from 1990 to 2017. Common presentation is pallor, fever and bleeding. The occurrence of myeloid sarcoma in extramedullary sites is rare. We present a unique case of AML with an unusual presentation of AML-induced superior vena cava (SVC) syndrome.

Case Presentation
A 26-year-old female with a history of hypertension presented with worsening facial swelling, chest pain, and shortness of breath. The patient’s medical history revealed multiple visits to other healthcare facilities for bilateral arm pain and chest discomfort, but a clear diagnosis had not been established. In her current visit, a computed tomography (CT) scan of the chest uncovered a sizable anterior superior mediastinal mass encasing the bilateral brachiocephalic vein and causing obstruction confirming the diagnosis of SVC syndrome. Additionally, deep vein thrombosis was observed in the form of bilateral brachiocephalic vein occlusion. Notably, a blood analysis revealed the presence of 30% blasts, raising suspicion of an underlying hematologic malignancy. The mass was subject to biopsy via cervical mediastinoscopy, and histopathological examination confirmed the presence of myeloid sarcoma, a highly atypical hematolymphoid malignancy positive for CD45, CD43, and myeloperoxidase (MPO), but negative for CD34, CD117, CD3, and CD20. Marrow examination further established the diagnosis of AML, showing 60% marrow involvement. Chemotherapy with cytarabine and daunorubicin was complicated by persistent fevers. The mediastinal mass was debrided, resolving the SVC syndrome. Blood count was closely monitored, and patient received irradiated blood and platelet transfusion. Treatment for complications (tumor lysis syndrome, disseminated intravascular coagulopathy, neutropenic fever, the pleural effusions) was provided. Future included consolidation therapy with high dose cytarabine (HIDAC) as an outpatient treatment, with the goal of eventual allogeneic hematopoietic stem cell transplantation (alloHSCT). The patient was educated about alloHSCT as a potential cure, along with its steps, toxicities, importance of suitable donor, and risk of relapse post-transplant; and scheduled for follow-up.

Discussion
This case report highlights that despite its common occurrence, AML may present with diverse and atypical clinical manifestations such as SVC syndrome, posing challenges in its diagnosis and timely management. As literature is scarce of this presentation of the disease, documentation of management is important for future analysis for optimal management. Awareness among medical practitioners and a high degree of suspicion may enhance detection and management of such rare presentations of AML.


A Unique case of Superior Vena Cava Syndrome in a patient with Acute Myeloid Leukemia

This is a case of 46-year-old male who presented to the hospital with complaints of unilateral inguinal pain and was eventually diagnosed with Diffuse Large B Cell lymphoma (DLBCL). Neoplastic proliferation of lymphoid cells primarily affecting the lymph nodes with infiltration of bone marrow, spleen and thymus is termed lymphoma. Lymphoma is further divided into Hodgkin and Non- Hodgkin. Extranodal involvement is less common with Hodgkin disease (HD). DLBCL is a type of Non-Hodgkin lymphoma. DLBCL can develop in the lymph nodes or in “extra nodal sites” (areas outside the lymph nodes) such as the gastrointestinal tract, testes, thyroid, skin, breast, bone, brain, or essentially any organ of the body. It may be localized (in one spot) or generalized (spread throughout the body). Despite being an aggressive lymphoma, DLBCL is considered potentially curable. This case highlights the fact that it is important to consider extra nodal lymphoma in the presence of certain imaging appearances in the appropriate clinical setting for the correct diagnosis, accurate staging, and optimal management. Although a definitive diagnosis is possible only with biopsy. I would like to highlight the uniqueness of this case as the patient had an atypical presentation, outlier in terms of age group and did not have any typical symptoms pertinent to lymphoma. Physicians should also consider malignancy under your differential when a patient presents with pain that is not explained by physical examination as the mass effect of any tumor can present as pain.

Atypical Presentation Of Non-Hodgkin B-Cell Lymphoma.

Background
The choroid, due to its rich vascular supply, is the most commonly affected ocular site for metastatic diseases. 
Most common cancers that result in choroidal metastasis are breast cancer (46-47% of cases) and lung cancer (21-29%). 
The most common type of lung cancer responsible for metastatic spread to choroid is adenocarcinoma. Small-cell lung cancer is a rare cause of choroidal metastasis.

Case Presentation
A 69-year-old male with history of COPD and heavy tobacco smoking initially presented with right-sided blurred vision and flashes of light. In the oncologist’s office, the patient was also found to have dyspnea, fatigue, anorexia and significant unintentional weight loss.
Fundus examination revealed irregular creamy white lesion and sub retinal fluid. 
The optical coherence tomography (OCT), ultrasound and fluorescein angiography of right eye showed vitreous detachment and a 10 mm x 10 mm x 3 mm irregular choroidal mass consistent with amelanotic metastatic choroidal disease.
CT scan of the chest W/WO contrast revealed a 5 cm x 4 cm right lower lobe mass, multiple bilateral pleural-based nodules, left lobe satellite nodules, subcarinal and anterior tracheal lymphadenopathy. CT scan of the abdomen and pelvis were negative for metastatic disease.
CT-guided biopsy of the right lower lobe mass showed high-grade tumor cells and immunohistochemistry showed positive staining for synaptophysin, CD56, TTF-1, and AE1/AE3 consistent with small-cell lung cancer.

Discussion
Lung cancer is a very uncommon cause of choroidal metastasis. Among all lung neoplasms, adenocarcinoma of the lung is the most common type which account for choroidal metastasis. 
SCLC is rarely reported to have spread to choroid. Most patients with SCLC with intraocular metastasis also had evidence of spread to bones and abdominal organs. Our patient did not show metastasis to solid organs or bones, but had widespread metastatic lesions in the thoracic cavity. Treatment of metastatic SCLC includes systemic therapy and local therapy. Systemic therapy includes chemotherapy with platinum-based regimens and target therapy e.g. atezolizumab or durvalumabc etc. Local radiotherapy also helps increase tumor response rate significantly.


Unilateral Choroidal Metastases as An Unusual Presentation for Small Cell Lung Cancer


Introduction : Immune checkpoint inhibitors (ICI) have been a breakthrough in the treatment of various types of cancers worldwide and have significant anti-tumor activity. But they are also linked to a number of immune-related adverse events (irAEs), including endocrinopathies(60%). Thyroid dysfunction and hypophysitis are the most common endocrine irAEs. Type 1 diabetes mellitus is a rare adverse event. Here we discuss a case of a patient with renal cell carcinoma(RCC) on Ipilimumab and nivolumab developing immune checkpoint inhibitors induced diabetes mellitus (ICI-DM).

Case presentation : A 62-year-old male, recently started on ipilimumab and nivolumab immunotherapy for Stage IV renal cell carcinoma, was admitted to the hospital due to altered mental status, malaise, nausea, vomiting, fevers, polydipsia, and polyuria commencing four days after therapy initiation.The clinical examination revealed a lethargic patient exhibiting Kussmaul respirations and mid-epigastric pain. He was mildly hypotensive. Lab findings revealed severe hyperglycemia with a plasma glucose of 1053 mg/dL, hyponatremia with a sodium level of 125 mmol/L, and hyperkalemia with a potassium level of 6.7 mmol/L. The patient showed signs of an increased anion gap metabolic acidosis with a bicarbonate level of 37 mmol/L, elevated lactic acid at 3.8 ( <2 mmol/L.), beta-hydroxybutyrate at 11.35(< 0.4-0.5), and lipase at 251(<240). Further laboratory investigation revealed an almost negligible C-peptide level of <0.2 (0.5 to 2.7 ng/mL), an A1c level at 6.5%, and a positive anti-GAD autoantibody result. A CT scan indicated mild inflammation in the peripancreatic and mesenteric root areas. The patient's diabetic ketoacidosis was managed with insulin infusion, and calcium gluconate administration. The patient was discharged on 55 units of long-acting insulin alongside 18 units of short-acting insulin to be taken with meals.

Discussion : ICI-DM is observed in 0.9% to 1.9% of cases. It occurs in patients who receive Anti-PD-1 (nivolumab) inhibitor therapy, with a higher incidence seen in those who receive combined anti-PD1 or anti-CTLA4 (Ipilimumab) therapy. By blocking the interaction between PD-1 and PD-L1, present on β-pancreatic cells, these inhibitors enable auto-reactive T cells to attack β-cells, triggering diabetes. The majority of patients present with diabetic ketoacidosis and require lifelong insulin therapy. Close monitoring of blood glucose levels should be considered in all patients receiving ICI therapy, regardless of their previous history of diabetes.

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Diagnostic and Therapeutic Complexities in a Case of Severe Acquired Factor 8 Deficiency

Next from 2023 AMA Research Challenge

A case report of autoimmune hemolytic anemia in a newly diagnosed patient with breast cancer Challenging transfusion dependency that interferes with neoadjuvant chemotherapy