Images in Immunotherapy and Precision Oncology: A Case Report of Neurofibromatosis-1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that primarily causes the growth of tumors along nerves. Additionally, the germline mutations involved in NF1 predispose patients to develop further malignancies. The mainstay initial treatment for these malignancies is surgical removal at diagnosis, although targeted therapies are under evaluation in the relapsed setting. We report a case of malignant peripheral nerve sheath tumor (MPNST), gastrointestinal stromal tumor (GIST), and pheochromocytoma in a patient with NF1 who presented with an infected right shoulder lesion that was confirmed to be spindle cell sarcoma via biopsy. She was treated with antibiotics; however, she rapidly deteriorated and opted for hospice care. NF1 germline mutations increase the risk of patients developing various types of cancer. Recent studies have shown that there is a role for using MEK inhibitors such as selumetinib for treating patients with NF1.

ALK-Positive Anaplastic Large Cell Lymphoma Associated With Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) has been rarely reported as a complication of anaplastic large cell lymphoma (ALCL), especially in the adult population. We herein present a case of a young woman who presented with multiorgan failure and disseminated intravascular hemolysis and was later found to have ALCL-associated HLH. We also review the current literature on ALCL-associated HLH in adult patients, with their respective treatments and outcomes. We discuss the challenges associated with the diagnosis of lymphoma in the setting of HLH and multiorgan failure. Further, given its high mortality rates, we highlight the importance of promptly identifying and treating the underlying etiology of HLH.

Carcinoma En Cuirasse: A Rare but Striking Cutaneous Manifestation of Metastatic Breast Cancer.

Carcinoma en cuirasse is a rare cutaneous metastatic presentation of breast cancer with a poor prognosis. We report a female in her 70s with a prior history of left breast ductal carcinoma in situ status post-radiation and lumpectomy who presented with skin thickening of the left breast and a few solid masses in bilateral breasts. Biopsy showed invasive ductal carcinoma of the left breast (estrogen receptor [ER]/progesterone receptor positive [PR], human epidermal growth factor receptor-2 [HER2] negative) and ductal carcinoma in situ of the right breast (ER/PR positive). She underwent a right breast lumpectomy; however, the left breast mastectomy was aborted due to the worsening of her skin findings on preoperative examination. A skin biopsy revealed poorly differentiated invasive ductal carcinoma. She was diagnosed with stage 4 breast cancer, specifically carcinoma en cuirasse. Systemic treatment was initiated, followed by a left breast mastectomy. A surgical biopsy was HER2-positive, and therefore anti-HER2 therapy was given. She remains on maintenance therapy with an excellent response at present.Any unexplained skin findings in breast cancer patients should prompt consideration of carcinoma en cuirasse. With ongoing treatment advances, many newer therapy options are available for metastatic breast cancer. Based on our case, we think that patients with this disease can have better outcomes.

A Rare Presentation of Concomitant Lung Disease and Hepatitis After Rituximab Treatment: A Case Report.

Rituximab (RTX) is a chimeric monoclonal antibody that is a standard component of treatment for all B-cell malignancies. The most common adverse events related to RTX are infusion-related reactions, such as fever, chills, urticaria, flushing, and headaches. However, RTX-induced lung disease (RTX-ILD) is a rare but potentially fatal adverse reaction, and diagnosing RTX-ILD is challenging, especially when accompanied by other rare adverse reactions, such as hepatitis. Here, we report a case of RTX-ILD with concomitant RTX-induced hepatitis in a 55-year-old man with follicular B-cell non-Hodgkin lymphoma who was on maintenance RTX therapy. The patient presented with a subacute, persistent dry cough, shortness of breath, fevers, and chills shortly after having traveled. Outpatient antibiotic therapy did not relieve symptoms, and laboratory studies revealed evidence of liver injury. A computed tomography (CT) of the chest showed predominately basilar airspace disease and ground glass opacities suggestive of multifocal pneumonia. Extensive infectious and autoimmune workups were negative. RTX-ILD with concomitant RTX-induced hepatitis was considered because antibiotic therapy did not resolve symptoms or improve signs of liver damage. Prednisone (1 mg/kg) led to symptom resolution and liver enzyme improvement. The patient underwent a 30-day steroid taper and the withholding of RTX infusions. A CT of the chest three months after discharge showed nearly resolved multifocal ground glass opacities. RTX-ILD should be considered after infectious and autoimmune etiologies have been ruled out for all patients on RTX therapy who experience symptoms of lung pathology or infection.

Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer.

Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.

Images in Immunotherapy and Precision Oncology: Angiosarcoma of the Spleen and Liver.

Primary splenic or hepatic angiosarcomas are ultra-rare and aggressive malignancies associated with poor prognosis. The mainstay treatments are surgical resection and chemotherapy. We report a case of angiosarcoma in a 50-year-old woman who presented with bruising, fatigue, ecchymosis, and hepatosplenomegaly. She was treated with the multi-kinase inhibitor sunitinib for 4 weeks before developing a splenic hemorrhage and succumbing. Recent studies have demonstrated the clinical benefit of immunotherapies in angiosarcomas. Additionally, sequencing techniques have showcased the diverse molecular aberrations involved in angiosarcomas, which offer opportunities for precision-matched targeted therapies such as inhibitors of the VEGF/VEGFR axis and PI3K/Akt/mTor pathway.

Complete Neurologic Recovery of Cerebral Fat Embolism Syndrome in Sickle Cell Disease.

Sickle cell disease is one of the most common inherited hemoglobinopathies diagnosed in the United States. Patients often present with severe anemia, pain crises, infections, and vaso-occlusive phenomena. Complications of these disorders can lead to significant debilitating morbidity and mortality. Fat embolism syndrome (FES) is a rare and devastating complication of sickle cell disease. It usually presents with a rapidly deteriorating clinical course, and the prognosis is dismal. We report a case of FES in a 19-year-old African American male with a history of sickle cell disease who presented with tonic-clonic seizures and was found to have multi-organ failure. FES was diagnosed 20 days from a presentation based on blood cytopenias and magnetic resonance imaging findings that were obscured at the initial presentation. We describe in this report, the patient's course from presentation until diagnosis and resolution. Our case is peculiar as the patient had a very good outcome without the need for red blood cell (RBC) exchange; instead, supportive treatment and simple RBC transfusions were enough to change the clinical course of this almost fatal syndrome.

Unusual Presentation of T-cell Large Granular Lymphocytic Leukemia.

Large granular lymphocytic (LGL) leukemia is a rare chronic lymphoproliferative disorder that can arise from T- or natural killer-cell lineages. It is an indolent disease that typically occurs in the sixth decade of life. Most cases of T-cell LGL leukemia (T-LGL) are associated with autoimmune disorders. Patients with T-LGL are generally asymptomatic; however, they can present with symptoms related to neutropenia, infections, and autoimmune disorders. Here, we report two cases of T-LGL in which the patients presented with liver dysfunction.

Clinical outcomes of COVID-19 in patients with sickle cell disease and sickle cell trait: A critical appraisal of the literature.

Individuals with sickle cell disease (SCD) and sickle cell trait (SCT) have many risk factors that could make them more susceptible to COVID-19 critical illness and death compared to the general population. With a growing body of literature in this field, a comprehensive review is needed. We reviewed 71 COVID-19-related studies conducted in 15 countries and published between January 1, 2020, and October 15, 2021, including a combined total of over 2000 patients with SCD and nearly 2000 patients with SCT. Adults with SCD typically have a mild to moderate COVID-19 disease course, but also a 2- to 7-fold increased risk of COVID-19-related hospitalization and a 1.2-fold increased risk of COVID-19-related death as compared to adults without SCD, but not compared to controls with similar comorbidities and end-organ damage. There is some evidence that persons with SCT have increased risk of COVID-19-related hospitalization and death although more studies with risk-stratification and properly matched controls are needed to confirm these findings. While the literature suggests that most children with SCD and COVID-19 have mild disease and low risk of death, some children with SCD, especially those with SCD-related comorbidities, are more likely to be hospitalized and require escalated care than children without SCD. However, children with SCD are less likely to experience COVID-19-related severe illness and death compared to adults with or without SCD. SCD-directed therapies such as transfusion and hydroxyurea may be associated with better COVID-19 outcomes, but prospective studies are needed for confirmation. While some studies have reported favorable short-term outcomes for COVID-19 patients with SCD and SCT, the long-term effects of SARS-CoV-2 infection are unknown and may affect individuals with SCD and SCT differently from the general population. Important focus areas for future research should include multi-center studies with larger sample sizes, assessment of hemoglobin genotype and SCD-modifying therapies on COVID-19 outcomes, inclusion of case-matched controls that account for the unique sample characteristics of SCD and SCT populations, and longitudinal assessment of post-COVID-19 symptoms.

A Rare Case of p190 BCR-ABL Chronic Myeloid Leukemia With a Very Good Response to Tyrosine Kinase Inhibitors.

The oncoprotein BCR-ABL has distinct fusion proteins generated from the Philadelphia chromosome translocation, depending on the site of the breakpoint on chromosome 22. The p210 is the hallmark of chronic myeloid leukemia. Only 1% - 2% of patients with chronic myeloid leukemia (CML) demonstrate p190 BCR-ABL. Imatinib mesylate, a tyrosine kinase inhibitor (TKI), specifically targets BCR-ABL, which brought a revolutionary era to the treatment of CML. Although the efficacy of imatinib is widely known, resistance to it has become a pressing challenge in the treatment of CML. CML patients harboring atypical e1a2 transcript (referred to as p190 BCR-ABL) show a poor and short-lived response to first-generation TKI therapy. Patients with p190 BCR-ABL CML should be identified as high-risk patients from the beginning to allow the best chance of a deep molecular response. These patients must be closely monitored during TKI therapy and should be treated upfront with a second-generation TKI. We report a case of p190 BCR-ABL CML with a good response to second-generation TKI.

Transient Anti-Phospholipid Antibodies in Two Patients With COVID-19.

We report two cases of coronavirus disease 2019 (COVID-19) in patients who developed pulmonary embolism and transient anti-phospholipid antibodies. At the time of presentation with acute pulmonary embolism, both patients had leukocytosis and increased levels of anti-cardiolipin antibodies, which resolved at testing 12 weeks after initial presentation. Studying cases of pulmonary embolism and increased anti-phospholipid antibodies in the context of COVID-19 could be one of the factors for elucidating the possible connection between severe acute respiratory syndrome coronavirus 2 infection, anti-phospholipid antibodies, and thrombosis.

Primary Pleural Extranodal Marginal Zone Lymphoma Presenting as Bilateral Chylothorax.

Here we describe a case of pleural extranodal marginal zone lymphoma presenting as bilateral chylothorax which has not been reported in the literature prior to this. Primary pleural lymphomas are a rare entity most commonly associated with chronic infections, autoimmune conditions or long-standing pyothorax which were not seen in this case. Chylous pleural effusions in this patient were successfully managed with chemotherapy for the underlying lymphoma.

Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease. One Center Urban Experience, Detroit, MI, USA.

The city of Detroit has a large population of individuals with sickle cell disease, and hospitals in Detroit have seen some of the highest numbers of cases of coronavirus disease-19 (COVID-19) in 2020. The purpose of this study was to examine the pathophysiological characteristics of COVID-19 in patients with sickle cell disease or trait to determine whether these patients have unique manifestations that might require special consideration. This retrospective analysis included 24 patients with confirmed COVID-19 and sickle cell disease or trait who were seen at the Henry Ford Hospital, Detroit, MI, USA, between March 1 and April 15 2020. Of the 24 patients, 18 (75.0%) had heterozygous sickle cell trait, one (4.0%) was a double heterozygote for Hb S (HBB: c.20A>T)/ß+-thalassemia (ß+-thal), four had sickle cell anemia (ßS/ßS) and one (4.0%) had Hb S/Hb C (HBB: c.19G>A) disease. A total of 13 (54.0%) patients required hospitalization. All four patients with sickle cell anemia, developed acute pain crisis. We observed one patient who developed acute pulmonary embolism and no patients developed other sickle cell associated complications. Additionally, three (13.0%) patients required packed red blood cell transfusion without the need of exchange transfusion, and one patient required admission to the intensive care unit (ICU), mechanical ventilation and subsequently died. Patients with sickle cell disease or trait and laboratory-confirmed COVID-19 had a generally mild, or unremarkable, course of disease, with lower chances of intubation, ICU admission and death, but with a slightly longer hospitalization.

Acute Splenic Sequestration Crisis in Hemoglobin SC Disease: Efficiency of Red Cell Exchange.

Acute splenic sequestration crisis (ASSC) is recognized as a serious complication of sickle cell disease in children. ASSC presents with progressive splenic enlargement, transfusion-dependent anemia, and, eventually, circulatory compromise. ASSC is rare in adult patients, thus making its management and outcome in adults not well-defined. The purpose of this article is to describe our experience in managing ASSC in an adult female with hemoglobin (Hb) SC disease. The patient underwent an automated red blood cell (RBC) exchange, thus avoiding a planned splenectomy. To the best of our knowledge, our case is the third report in the literature on the use of RBC exchange in adults with HbSC disease and ASSC. RBC exchange should be considered in adults with HbSC disease with ASSC not responding to simple transfusion; a treatment that could alleviate patients' symptoms and avoid splenectomy complications, especially in young patients.

A rare case of follicular lymphoma transformed to a high-grade B-cell lymphoma in orbit.

Transformation of lymphoma is an infrequent phenomenon, and involvement of the eye as such is even uncommon. Histological transformation in patients with follicular lymphoma who were previously treated with immune-chemotherapy carry a poor outcome. Here, we illustrate such a case with aggressive histological transformation from a low-grade lymphoma.

Utilization of the 21-Gene Recurrence Score in a Diverse Breast Cancer Patient Population: Development of a Clinicopathologic Model to Predict High-Risk Scores and Response to Neoadjuvant Chemotherapy.

INTRODUCTION: The 21-gene expression profile [Oncotype DX Recurrence Score (RS)] stratifies benefit from adjuvant chemotherapy in hormone receptor (HR)-positive, HER2/neu-negative, node-negative breast cancer. It is not routinely applied to predict neoadjuvant chemotherapy (NACT) response; data in diverse patient populations also are limited. We developed a statistical model based on standard clinicopathologic features to identify high-risk cases (RS > 30) and then evaluated ability of predicted high RS to predict for NACT downstaging. METHODS: Primary surgery patients with Oncotype DX RS testing 2012-2016 were identified from a prospectively-maintained database. A RS predictive model was created and applied to a dataset of comparable NACT patients. Response was defined as tumor size decrease ≥ 1 cm. RESULTS: Of 394 primary surgery patients-60.4% white American; 31.0% African American-RS distribution was similar for both groups. No single feature reliably identified high RS patients; however, a model accounting for age, HR expression, proliferative index (MIB1/Ki67), histology, and tumor size was generated, with receiver operator area under the curve 0.909. Fifty-six NACT patients were identified (25 African American). Of 21 cases with all relevant clinicopathology, 14 responded to NACT and the model generated high-risk RS in 14 (100%); conversely, of 16 cases generating high-risk RS, only 2 did not respond. CONCLUSIONS: Predictive modelling can identify high RS patients; this model also can identify patients likely to experience primary tumor downstaging with NACT. Until this model is validated in other datasets, we recommend that Oncotype-eligible patients undergo primary surgery with decisions regarding chemotherapy made in the adjuvant setting.

Idiopathic erythrocytosis in dialysis patients: a case report and literature review.

Anemia is a common complication in end-stage renal disease (ESRD) patients. On the other hand, idiopathic erythrocytosis is extremely rare, with only a few cases reported in the literature. We present a case of erythrocytosis that developed after initiating hemodialysis. A 68-year-old male with a history of ESRD secondary to diabetes presented with erythrocytosis that started a few months after initiating dialysis in the absence of having received erythropoietin-stimulating agents or iron supplements. His erythropoietin level was elevated, with a negative JAK2 mutation. Blood gases showed normal oxygen and CO(2), with slightly elevated carboxyhemoglobin. Tiny foci in both kidneys were noted, representing vascular calcifications or renolithiasis. There was no radiological evidence of neoplasms or cysts. After excluding secondary causes, a diagnosis of idiopathic erythrocytosis was made. The patient underwent intermittent phlebotomies during dialysis, and his hemoglobin went from 18.5 to 14 mg/dl. Erythrocytosis in ESRD patients is very rare. So far, there is no complete understanding of the underlying pathophysiology; however, there seem to be multiple possible reasons for an increased erythropoietin level. Phlebotomy is a successful and easy way to control erythrocytosis in such patients. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, currently being used in posttransplant erythrocytosis, might also be considered.

Thrombosis in VonWillebrand disease.

OBJECTIVE: To date, only a few case studies have reported occurrence of thrombosis in patients with VonWillebrand disease (VWD). No studies have looked at its incidence in this patient population. The aim of this study was to test our hypothesis that decreased VonWillebrand factor (VWF) levels confer a protective effect on arterial and venous thrombosis. METHODS: This is a retrospective cohort study including patients (n=350) with the ICD-9 code of VWD who were identified from our hospital database over a period of 25 years, out of which 198 patients were included in the final sample. A parallel control sample without VWD matched for age, sex, hypertension, hyperlipidemia, atrial fibrillation and diabetes mellitus was also obtained from the hospital database. The primary outcomes were incidence of diagnosis of symptomatic arterial and venous thrombosis. The results were computed using multivariate conditional logistic regression analysis and proportions were compared using McNemer's Chi - square test. RESULTS: Out of 198 patients (mean age 44.2 ± 17.5, women 72%) with VWD, 170 (86%) were VWD type 1, 21 (10%) were type 2 and 7 (3%) were type 3. VWD was found to be an independent protective predictor from arterial thrombosis (OR 0.28, 95% CI 0.14-0.54, p<0.0001), more so in CAD (OR 0.28, 95% CI 0.12-0.64, p=0.002) than in CVD (OR 0.28, 95% CI 0.10-0.77, p=0.01). However this was not the case in venous thrombosis (p=0.42). CONCLUSION: In a population of relatively younger individuals with VWD, our study suggests a reduced incidence of arterial thrombosis but not of venous thrombosis. This brings up the possibility that there could be other pathways or factors involved in arterial and venous thrombosis. To our knowledge, this is the first large observational study that has provided insight into the thrombotic disease in this group of patients.

Can rituximab replace splenectomy in immune thrombocytopenic purpura?

AIM: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction. Standard practice is to initiate treatment with corticosteroids, followed by splenectomy. Most published literature for responses from rituximab is in patients with chronic refractory ITP, who have failed multiple prior treatments, including splenectomy. We therefore decided to analyze our patient population with ITP who had been treated with rituximab, mainly as a second line treatment regimen prior to splenectomy. METHODS: We performed a retrospective chart review of patients with a diagnosis of ITP who had been treated with rituximab between January 2001 and December 2006 at our institution. RESULTS: 18/29 patients (62%) had a CR, 2/29 (7%) patients had a PR, representing an overall response rate of 69%. The average time to response was 5 weeks and all patients have maintained their response for more than 12 months after treatment with rituximab. CONCLUSION: Our study shows higher CR, comparable overall response rates, but with a longer duration of response when compared to the published literature.