United States

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. 


AMA Research Challenge 2023

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

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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.

A Case of New-onset Immunotherapy-mediated Diabetes Mellitus Presenting as Diabetic Ketoacidosis and Autoimmune Pancreatitis.

Tumor Lysis Syndrome (TLS) is an oncologic emergency that requires prompt recognition and treatment. It occurs due to the release of nucleic acids, potassium, and phosphate systemically. It is seen more commonly in hematologic than solid malignancies. Dehydration, acute kidney injury, high tumor burden are a few of the risk factors that predispose an individual to TLS. Here, we present a case of TLS in a patient with stage IV ovarian cancer. Our patient presented with nausea, vomiting, and was noted to have acute kidney injury, small bowel obstruction and hydronephrosis. She received cytoreductive chemotherapy and she developed hyperuricemia, hyperkalemia, hyperphosphatemia, and acute kidney injury and was diagnosed to have TLS. She received rasburicase and her creatinine improved. Due to a slower tumor doubling time and delayed chemotherapy effect, TLS is less commonly seen in solid malignancies. In our patient her high tumor burden, chemotherapy administration, acute kidney injury and dehydration predisposed her to tumor lysis. It is important to identify patients who could undergo tumor lysis and risk stratify them since mortality can be as high as 40% in these patients.

Unraveling the Mystery: A case of tumor lysis in a patient with ovarian cancer


Background: Pigmented Villonodular Synovitis (PVNS) is a rare, benign neoplastic
condition affecting the synovial membrane of joints, bursae, and tendons. It is divided into diffuse and localized PVNS (female predilection). The knees are commonly affected, followed by the hips and ankles. Symptoms include pain, swelling and stiffness around the affected joint with recurrent atraumatic hemarthrosis. Etiology includes chromosomal translocation involving chromosome 1p13 causing over-expression of CSF-1 in neoplastic cells. The patients are often diagnosed between the ages of 20-50 years.

Case Presentation: A 24 year-old female presented with insidious onset of pain, swelling and stiffness of her left knee for 5 months. MRI of the left knee with and without contrast was done with findings suggestive of PVNS along the posterior aspect of the knee with moderate joint effusion. Initial blood-work was performed to establish the baseline results. Pexidartinib 800mg/day was started with regular monitoring for possible hepatotoxicity. 15 days into the treatment, the patient’s symptoms resolved, but the patient developed hypopigmented patches over her face, depigmentation of body hair and loss of appetite. After 2 months of therapy, her creatinine was found to be elevated, hence the dose of Pexidartinib was decreased to 600mg/day. She was also diagnosed with iron deficiency anemia for which 15 cycles of iron infusions were given. MRI 4 months after the therapy
showed images of near complete resolution with no joint effusion. However, a small
amount of hemosiderin deposition was evident, therefore, residual PVNS was not
excluded. Routine labs showed elevated AST/ALT levels, hence Pexidartinib was
discontinued. The patient returned 4 months later with similar complaints. MRI showed findings of recurrent PVNS along the posterior margin of Hoffa's fat pad, posterior joint capsule, intercondylar notch, and popliteus myotendinous junction. Large joint effusion and diffuse synovitis was present. Pexidartinib 250mg was started again, after reviewing her recent labs. She is currently tolerating the medication without any concerns.

Discussion: PVNS is a rare disorder that requires prompt management as it can cause morbidity.
MRI is the standard imaging modality used in both diagnosis and to assess recurrence. The mainstay treatment is surgical excision with total synovectomy but due to high recurrence rate (8-60%), other systemic therapies are being investigated. In August 2019, FDA approved the use of Pexidartinib for PVNS. Pexidartinib is a tyrosine kinase inhibitor that targets CSF1R. Liver function tests are performed periodically to monitor hepatotoxicity with dosage being reduced or discontinued accordingly.

Relapse of pigmented villonodular synovitis

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**Abstract:**



Numerous Recurrent Venous Thromboembolisms in the Setting of Severe Obesity and Anticoagulation: A Case Report

We herein report a case of a 24-year-old female who presented to her primary care physician with the chief complaint of increased forgetfulness and brain fog. Further history revealed that she had also been having shortness of breath, nausea/vomiting, fatigue, myalgias, and a 20 lb weight loss. A chest x-ray was ordered and was read as cardiomegaly with severe pulmonary edema. The patient was notified by her PCP to immediately present to an Emergency Department. Upon initial presentation to the hospital, the patient was normotensive, mildly tachycardic at 104 bpm, with oxygen saturation of 92% on room air. Her BMI was 18.8 kg/m2. Physical examination was significant for an ill-appearing female with generalized weakness and mild respiratory distress. She did not have any cardiac murmurs, her lungs were clear to auscultation, and she did not have any rashes. The most pertinent laboratory findings included leukocytosis (14.31 k/uL), normocytic anemia (9.7g/dL), elevated alkaline phosphatase (578U/L), and elevated C-reactive protein (13.38 mg/dL). CT chest/abdomen/pelvis with contrast revealed severe diffuse miliary lung disease, mild bilateral hilar adenopathy, a large pericardial effusion, and ill-defined bony lesions throughout the entire skeleton. CT head without contrast showed multiple calcifications scattered throughout the brain. Given the typical miliary pattern and concern for disseminated tuberculosis, she was empirically started on RIPE therapy. Pericardiocentesis was urgently done due to finding of large circumferential effusion on transthoracic echocardiography concerning for tamponade physiology. The cytology from the pericardial fluid was suspicious for malignancy. Iliac bone biopsy ultimately confirmed metastatic adenocarcinoma consistent with lung primary. RIPE therapy was discontinued, and the patient was started on carboplatin and pemetrexed. After significant improvement in functional capacity, the patient was discharged home with her family after 31 days in the hospital. She is currently being treated with pembrolizumab and pemetrexed and her disease burden has remained stable for 9 months now.

Lung cancer is extremely rare in young adults <35 years old. In this population, it predominantly presents as non-small cell lung cancer (NSCLC) or more specifically, as adenocarcinoma. While cough is the most common presenting symptom (50-75%) in older patients, non-specific symptoms mimicking other pathologies are often present in younger patients with NSCLC. The most common gene mutations are EGFR, KRAS, FGFR1 and ALK, not necessarily hereditary.

Miliary pattern of lung disease can be seen in a handful of etiologies. These include infectious diseases such as tuberculosis and disseminated fungal infections, autoimmune diseases like sarcoidosis, environmental diseases such as silicosis, and neoplastic diseases such as adenocarcinoma and metastasis. The most common of these, as expected, is tuberculosis. In a young patient without risk factors presenting with symptoms and findings typical of an infectious process, we need to be vigilant of less common, unexpected etiologies and keep a broad differential.

Miliary Disease in a 24-year-old Female- An Unexpected Diagnosis

Background
In the course of chronic Hepatitis C virus (HCV) infection, 70% of patients have one or more extrahepatic manifestations. Therefore, patients can present with a spectrum of clinical symptoms that correlate to mixed cryoglobulinemia, non-Hodgkin’s lymphomas, and more. More specifically, the concurrence of hematologic malignancy and membranoproliferative glomerulonephritis (MPGN) can be fatal. Here we report a lethal cascade of extrahepatic manifestations from untreated HCV infection. 

Case Presentation
A 73-year-old female with history of HCV (diagnosed 16 years ago, untreated due to insurance barriers), chronic polyarthralgia, and splenic marginal zone lymphoma (diagnosed 8 years ago, lost to follow-up) presented with lower extremity edema and worsening joint pain. She had previously been prescribed opioids and prednisone for polyarthralgia. The patient was found to have acute kidney injury, elevated rheumatoid factor, decreased C3 and C4, and sub-nephrotic range proteinuria. Worsening arthralgia and renal impairment were hypothesized to be secondary to HCV-related cryoglobulinemia, and she was advised to follow up for HCV treatment and renal biopsy. Two weeks later, she presented again with new lower extremity purpura. She subsequently developed sepsis, worsening kidney failure requiring hemodialysis, and metabolic encephalopathy requiring intubation. After two days of intravenous methylprednisone for presumed mixed cryoglobulinemia vasculitis, the patient’s mental status improved, and renal and skin biopsies were done. Renal biopsy showed MPGN with evidence of pseudothrombi from known cryoglobulins, and skin lesions were consistent with leukocytoclastic vasculitis. Despite plans to treat the patient’s underlying HCV, the patient’s clinical condition continued to deteriorate, and her family decided to transition her to comfort care. She passed away shortly after. 

Discussion
The concurrence of cryoglobulinemic MPGN in HCV patients with splenic marginal zone lymphoma is rare. While the lymphomagenic role of HCV is debated, literature demonstrates that antiviral treatment could be first-line therapy in HCV-associated lymphomas. However, connecting this patient’s clinical signs and symptoms to her previously diagnosed HCV was complicated by the patient’s use of opioids and prednisone for pain. As these medications improved the patient’s polyarthralgia, it seemed as though agents prescribed for presumed arthritis flares likely masked an underlying cryoglobulinemia. In patients with extrahepatic manifestations and atypical features of cryoglobulinemia, a full evaluation for the underlying cause is critical. Lack of viral diagnosis and delay to treatment can result in significant morbidity and cumulative organ failure. Unfortunately for this patient, serological signs of her extrahepatic manifestations presented themselves early, meaning this fatal outcome could have been avoided with early antiviral therapy. 


Failed to turn the tide: Chronic hepatitis C related cryoglobulinemia, lymphoma, and membranoproliferative glomerulonephritis

Background:
Chordae tendineae rupture (CTR) has been linked to several factors as hypertension, rheumatic fever, and ischemic heart disease. Here we report a patient with CTR during COVID-19 infection.

Case
A 79-year-old man with non-stenotic coronary artery disease, ischemic cardiomyopathy with diastolic dysfunction, rheumatic heart disease with chronic moderate mitral regurgitation, pulmonary hypertension, paroxysmal atrial fibrillation on apixaban, hypertension, familial hypercholesterolemia, and obstructive sleep apnea presented with progressive worsening of dyspnea, palpitations, orthopnea, and lightheadedness for 6 months duration with acute deterioration 2 hours before admission.

He was hemodynamically stable but was hypoxic with saturation at 89%, requiring 2L O2 by nasal cannula. On examination, a holosystolic murmur was auscultated at the cardiac apex. The rest of examination was normal.

EKG showed sinus rhythm at 73 BPM without ST changes. Laboratory investigations were within normal limits except for Brain natriuretic peptide, which was 3160 pg/mL. He tested positive for COVID-19. Chest x-ray revealed patchy perihilar, right lower lung zone opacities, and a minor right-sided pleural effusion. Transesophageal echocardiography showed moderate to severe mitral valve regurgitation, left ventricular hypertrophy with normal left ventricular ejection fraction at 60%. Records of previous imaging were not available.

Upon cardiac catheterization, high-grade proximal stenosis was detected in the left anterior descending artery and ostial small circumflex; flail posterior mitral valve leaflet with ruptured chordae tendineae, redundant and hypermobile anterior mitral leaflet and myxomatous degeneration of the mitral valve was noted. He underwent mitral valve replacement with mosaic porcine bioprosthesis, single-vessel bypass grafting in the left anterior descending artery with left internal mammary graft, left-sided maze atrial ablation atricure cryoprobe, and Mitra Clip placement at the base of left atrial appendage after a week of clinical improvement with diuresis, nirmatrelvir/ritonavir, and holding apixaban. Apixaban was not restarted postoperatively due to poor general health and high fall risk, and he was discharged to rehabilitation.

Discussion
Mitral regurgitation (MR) affects 9.3% of Americans 75 and older. Primary MR is caused by mitral valve prolapse from CTR. CTR can be of primary or secondary origin. Hypertension is determined to be an independent predictor of primary CTR. Acute rheumatic fever, osteogenesis imperfecta, ischemic heart disease, chronic rheumatic valvular disease, and bacterial endocarditis are causes of secondary CTR. Myxomatous degeneration is underreported since the microscopic investigation is not routinely performed. The posterior chorda is more commonly affected than the anterior chorda. Mild mitral CTR often entails the separation of a single chorda, resulting in limited hemodynamic sequelae requiring no treatment. Multiple chordae ruptures may cause moderate-to-severe MR requiring surgical intervention. The course of the presentation can be acute or progressive. MR severity grading influences clinical decisions, prognosis, and treatment plans. Echocardiography is the most routinely conducted noninvasive MR test.
In literature, COVID-19 infection is linked to cardiovascular complications as myocarditis, myocardial infarction, and cardiogenic shock. At this juncture, there is not enough evidence to attribute the development of CTR to COVID-19 infection, although a causal association is possible.

Conclusion
This case highlights a complex presentation of Chordae tendineae rupture with concurrent Covid-19 infection.

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

Next from AMA Research Challenge 2023

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