History Of Chronic Lymphocytic Leukemia Research Articles

An extranodal Richter’s syndrome presenting with cardiac diffuse large B-cell lymphoma: a case report

BackgroundRichter’s syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves lymph nodes and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose.Case presentationA 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm × 37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma.ConclusionsWe present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

Thymoma Involved by Small Lymphocytic Lymphoma (SLL): A Rare and Challenging Diagnosis

Abstract Introduction/Objective Thymoma is a malignant neoplasm arising from the epithelial cells of the thymus. It usually affects patients between the fourth and sixth decades of life. There is a strong association of thymoma with myasthenia gravis and other paraneoplastic syndromes Thymic epithelial tumors are the most common tumors of the anterior mediastinum; however, lymphomas frequently present as mediastinal masses. Concurrent thymoma and lymphoma affecting the thymus is very rare. Methods/Case Report A 79-year-old woman with a history of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) presented with night sweats and weight loss. Chest CT revealed small pulmonary nodules, a 3.3 x cm anterior mediastinal mass and enlarged hilar lymph nodes. Fine needle aspiration (FNA) of the mass revealed a mixture of lymphocytes and epithelial cells. Flow cytometry showed a monoclonal B-cell population, and double CD4/CD8-positive T-cells consistent with thymocytes. Core biopsy showed scattered neoplastic epithelial cells interspersed among densely packed small lymphocytes. Scattered and small clusters of epithelial cells were highlighted by the CK AE1/3 immunostain. CD3 and PAX5 showed the thymocytes and infiltrating B-cells, respectively. Based on cytomorphologic, flow cytometric, histopathologic, and immunohistochemical findings, the diagnosis of thymoma, type B2 involved by SLL was rendered. Results (if a Case Study enter NA) N/A Conclusion A multimodality diagnostic work-up integrating cytomorphology, flow cytometry and immunohistochemistry allowed recognizing this unusual association.

The Utility of EBUS-Guided Transbronchial Forceps Biopsy With or Without an Electrocautery Knife for the Diagnosis of Mediastinal and Hilar Lymphadenopathy.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been shown to have a high diagnostic yield for mediastinal and hilar lymph node sampling, particularly in diagnosing and staging non-small cell lung cancer. However, the diagnostic yield is lower in patients with granulomatous and lymphoproliferative disorders. We prospectively compared the feasibility, safety, and diagnostic yield of EBUS-guided lymph node forceps biopsy (EBUS-TBFB) with electrocautery knife compared to EBUS-TBNA of lymph nodes in patients with suspected granulomatous and lymphoproliferative disease. Patients over 18 years of age with mediastinal/hilar lymph node >10 mm in size in short axis (on CT chest) who had suspected sarcoidosis/lymphoma radiologically/clinically were included in the study. Patients had EBUS-TBNA first with 21 or 22G needles which were followed by biopsy of the node with small forceps (EBUS-TBFB) through the same aspiration site to obtain samples. Electrocautery knife at 20W was used in patients where mucosal penetration was difficult, followed by passage of forceps through that site. A total of 30 patients were enrolled in the study, of which 25 patients underwent EBUS-TBFB. Eight patients had a history of lymphoma, one patient had history of squamous cell carcinoma, and one patient had history of chronic lymphocytic leukemia. A 22 gauge needle was used for aspiration in all the cases that were performed, and 1.5 mm or 1.8 mm forceps were used for the biopsy.The use of electrocautery knife at 20W (Olympus America Inc.) was required in 10/25 patients.The EC knife allowed all 10 of those to have successful entry of forceps into the lymph node. The cytology (aspiration from EBUS needle) and histopathology (from forceps) were concordant in 17 patients while it was discordant in eight patients. One patient developed pneumomediastinum after needle and forceps biopsy that required no intervention. EBUS-guided forceps biopsy is a safe procedure. EC knife did successfully allow forceps entry into the lymph node in all EC knife procedures. The diagnostic yield was 73% (22/30) which improved to 86% (26/30) when both techniques were combined (TBNA and TBFB).

Neuroaspergillosis: Challenging Diagnosis and Management (P10-10.002)

<h3>Objective:</h3> N/A <h3>Background:</h3> Invasive fungal infections are associated with increased morbidity and mortality among immunocompromised patients, particularly due to non-specific symptoms, difficulty and delay in diagnosis, and limited therapeutic options. Aspergillosis is the leading cause of invasive fungal infections. Neuroaspergillosis commonly arises from hematogenous dissemination from invasive lung infection in immunocompromised patients and can lead to brain abscess, meningitis, and stroke from angioinvasion. Cerebral aspergillosis has a poor prognosis. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 62-year-old man with history of chronic lymphocytic leukemia and SARS-CoV-2 pneumonia presented with acute onset right-sided weakness. Head CT exhibited bilateral hypodensities concerning for emboli or metastases. Brain MRI revealed numerous bihemispheric T2 hyperintensities with vasogenic edema. Some lesions demonstrated restricted diffusion and contrast enhancement. At this point, differential diagnosis included septic emboli, abscess, and metastatic disease. TTE did not show signs of infective endocarditis. CT of the chest, abdomen, and pelvis revealed an irregular, centrally necrotic opacity. Bronchoscopy with bronchial lavage was performed, and biopsies were negative for malignancy and positive for Aspergillus species. The patient was started on amphotericin and was switched to voriconazole due to poor tolerance. Because of mental status fluctuation caused by edema, glucocorticoids were used concurrently with antifungal treatment. He had serial head CTs which initially revealed increasing edema and increasing effacement of the left lateral ventricle and third ventricle with development of early hydrocephalus. Neurosurgery was consulted, and family declined any surgical intervention. He was managed with dexamethasone 4 mg daily, and he demonstrated improvement in symptoms and edema on imaging in 1 week. <h3>Conclusions:</h3> In immunocompromised patients found to have multiple brain enhancing lesions with unrevealing preliminary work-up, invasive <i>Aspergillosis</i> infection must be considered. Here, we present a case of aspergillus managed concurrently with steroids and voriconazole. Despite the infectious source, there appears to be a role for steroids in the management of neuroaspergillosis. <b>Disclosure:</b> Dr. Jaworski has nothing to disclose. Dr. Reyes has nothing to disclose. Dr. Yacoub has nothing to disclose.

Embolic Stroke Following Intravenous Ozone Therapy (P2-5.007)

<h3>Objective:</h3> NA <h3>Background:</h3> Ozone therapy via autohemotherapy has become among the alternative therapies purported to treat chronic lymphocytic leukemia. Ozone gas is injected into blood drawn from the patient, which is mixed then transfused back intravenously. Due to the infrequent use of this modality, it has not been previously reported as a risk factor for stroke. <h3>Design/Methods:</h3> A 62-year-old man with a history of chronic lymphocytic leukemia, chronic migraines, hypertension, and diabetes mellitus type II presented with acute left arm numbness followed by weakness during administration of intravenous (IV) ozone. Shortly after, he developed a migrainous headache, which is typical for him. Neurological examination revealed left upper and lower extremity weakness. CT head and CT angiography were performed and were unremarkable. The patient was treated with IV tPA. He continued to have left-sided weakness and numbness along with a migrainous headache after the intervention. MRI of the brain revealed multiple bilateral frontal and parietal infarcts. Dual antiplatelet therapy was initiated. Echocardiogram revealed a large patent foramen ovale (PFO) with a right-to-left shunt. A transcranial doppler with bubble study revealed multiple high intensity transient signals post valsalva maneuvers, supporting the diagnosis of paradoxical emboli. Patient eventually underwent successful outpatient PFO closure without complications. <h3>Results:</h3> NA <h3>Conclusions:</h3> This case presents a rare cause of stroke following IV injection of ozone. Acute stroke following ozone therapy has not been previously reported in the literature. The pathogenesis remains unknown, although it is theorized that it may have been due to IV administration of ozone-mixed blood in the presence of a PFO. It is imperative to recognize this phenomenon as a potential risk of embolic stroke in patients receiving IV ozone treatment. <b>Disclosure:</b> Dr. Kokash has nothing to disclose. Dr. Zahra has nothing to disclose. Dr. Singh has nothing to disclose. Dr. Yacoub has nothing to disclose. Dr. Leary has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Clinical Research Institute. Dr. Leary has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Baim Clinical Research Institute. Dr. Leary has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Syneos Health. Dr. Leary has received publishing royalties from a publication relating to health care.

Abstract 6523: A case of stage I HPV-mediated oropharyngeal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test

Abstract There are no routine screening tests for head and neck (H&amp;N) cancers, which account for approximately 4% of all cancers in the US. Risk factors for oropharyngeal cancer include smoking and human papillomavirus (HPV) infection. An MCED test that uses a cell-free DNA-based targeted methylation assay and machine learning classifiers to detect a shared cancer signal and predict the cancer signal origin (CSO) is available as a complement to existing single-cancer screening tests. If a cancer signal is detected, the positive result is reported with 1 or 2 CSO prediction(s). We report here a tonsil cancer case detected using an MCED test and review the CSO-guided diagnostic journey. An asymptomatic 74-year-old White male (BMI: 29.9 kg/m2) with history of chronic lymphocytic leukemia (CLL; Rai stage 0; 13q, CD38, and ZAP-70 negative; no treatment was needed) 17 years prior and papillary thyroid cancer (stage IVa; pT3N1bM0; thyroidectomy and radiation therapy; no recurrence) 8 years prior was screened using the MCED test. Patient had an elevated PSA level (9-10 ng/mL) and was a nonsmoker. Fifteen days after a blood sample was collected for analysis, a positive test result (CSO prediction=H&amp;N) was communicated to the patient (Day 1). PET showed abnormal uptake in the right tonsil (Day 28). The patient was referred for an ENT consult and underwent a right lymph node biopsy (Day 54). The biopsy showed invasive moderately differentiated SCC, non-keratinizing, forming a 3 × 2.1 × 1.2 cm mass (Day 57). Patient underwent right tonsillectomy (the surgical margins were negative for invasive or in situ carcinoma) and lymph node dissection (Day 57). The cancer was diagnosed as HPV-mediated p16+, pT2, pN1, cM0 (stage I) SCC of the oropharynx (Day 57). No chemotherapy or radiation was required due to the early stage of detection. The patient will follow-up with ENT and radiation oncology. The MCED test detected a cancer signal and predicted an accurate CSO for an asymptomatic individual with stage I HPV-mediated oropharyngeal SCC. Notably, despite a history of CLL and an elevated PSA level, the test accurately predicted CSO leading to a directed workup diagnosing asymptomatic cancer in less than 2 months, while the cancer was still at stage I. In the case-control Circulating Cell-free Genome Atlas study, the MCED test sensitivity to detect a cancer signal was 63% in stage I H&amp;N cancer. The use of this MCED test led to detection of cancer in a patient with CLL history and treatment (surgery without complications and without chemotherapy or radiation) with curative intent. Citation Format: Janet Vittone, Julia Feygin, Jason Carey. A case of stage I HPV-mediated oropharyngeal squamous cell carcinoma (SCC) diagnosed using a multi-cancer early detection (MCED) test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6523.

T cell receptor gene repertoire profiles in subgroups of patients with chronic lymphocytic leukemia bearing distinct genomic aberrations.

Microenvironmental interactions of the malignant clone with T cells are critical throughout the natural history of chronic lymphocytic leukemia (CLL). Indeed, clonal expansions of T cells and shared clonotypes exist between different CLL patients, strongly implying clonal selection by antigens. Moreover, immunogenic neoepitopes have been isolated from the clonotypic B cell receptor immunoglobulin sequences, offering a rationale for immunotherapeutic approaches. Here, we interrogated the T cell receptor (TR) gene repertoire of CLL patients with different genomic aberration profiles aiming to identify unique signatures that would point towards an additional source of immunogenic neoepitopes for T cells. TR gene repertoire profiling using next generation sequencing in groups of patients with CLL carrying one of the following copy-number aberrations (CNAs): del(11q), del(17p), del(13q), trisomy 12, or gene mutations in TP53 or NOTCH1. Oligoclonal expansions were found in all patients with distinct recurrent genomic aberrations; these were more pronounced in cases bearing CNAs, particularly trisomy 12, rather than gene mutations. Shared clonotypes were found both within and across groups, which appeared to be CLL-biased based on extensive comparisons against TR databases from various entities. Moreover, in silico analysis identified TR clonotypes with high binding affinity to neoepitopes predicted to arise from TP53 and NOTCH1 mutations. Distinct TR repertoire profiles were identified in groups of patients with CLL bearing different genomic aberrations, alluding to distinct selection processes. Abnormal protein expression and gene dosage effects associated with recurrent genomic aberrations likely represent a relevant source of CLL-specific selecting antigens.

368: ANGIOEDEMA PREVENTING EXTUBATION IN A CASE OF ACQUIRED C-1 ESTERASE DEFICIENCY

Introduction: Acquired C1 esterase deficiency is a rare, life-threatening phenomenon that has been reported in association with lymphoproliferative and autoimmune disorders. Diagnosis is made based on the clinical presentation of angioedema and low C1 and C1q esterase inhibitor activity in a patient without a previous hereditary diagnosis. Treatment is aimed at addressing the underlying condition and plasma-derived C1 esterase inhibitor (C1-INH) concentrate, but clinical response can vary. Description: 75 year-old female with a past medical history of chronic lymphocytic leukemia (CLL) presented with spontaneous mouth and neck swelling unrelieved by antihistamines. Epinephrine and Solumedrol were administered, however the neck swelling worsened and the patient was intubated for airway protection. CT imaging of the neck revealed extensive subcutaneous neck edema. Attempts at extubation were limited by the patient’s persistent angioedema which was visualized by bronchoscopy. Glucocorticoids were ineffective as the patient had a reported allergy to Prednisone, therefore were further avoided. C1 esterase inhibitor (C1-INH) function was initially low at 7mg/dL, and repeat remained low at 10mg/dL with a C4 of .7mg/dL. C1q later returned low at < 1.2Eq/mL. The patient did not improve after treatment with plasma-derived C1-INH (Berinert). She eventually required tracheostomy placement, but had difficulty with subsequent downsizing due to persistent laryngeal edema with limited therapeutic options. Eventually, after 4 weeks, the patient was successfully decannulated. Discussion: There are no definitive guidelines for treatment of acquired C1 esterase deficiency, however therapies often follow the same course for hereditary forms including plasma-derived C1-INH. Often, these patients may not respond or require increased doses. If Berinert is ineffective, some immunologists and allergists have seen favorable outcomes and recommend treatment with the kallikrein inhibitor, ecallantide and the bradykinin B2 antagonist icatibant. To date, therapies targeted at prevention of angioedema in acquired cases have not been as successful as in hereditary forms, therefore, treatment is directed at the underlying condition, such as immunotherapy or chemotherapy for CLL.

68Ga-DOTATATE PET/CT Incidentally Detects Relapsed Chronic Lymphocytic Leukemia in Patient With Metastatic Neuroendocrine Tumor.

A 54-year-old man with metastatic well-differentiated neuroendocrine tumor of the pancreas underwent 68Ga-DOTATATE PET/CT scan to evaluate treatment response. Patient was known for remote history of chronic lymphocytic leukemia (CLL), previously treated. Scan revealed diffusely increased abnormal tracer uptake throughout the marrow of the axial and proximal appendicular skeleton. Bone marrow biopsy revealed relapsed CLL. We present a rare case of relapsed CLL incidentally detected on 68Ga-DOTATATE PET/CT.

Merkel cell carcinoma: a case report

Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine malignancy that presents as a persistent red-purplish, asymptomatic and rapidly growing nodule. It typically affects sun-exposed skin of white elderly individuals. In addition, risk factors for Merkel cell carcinoma include immunosuppression, as well as the presence of multiple myeloma or a history of chronic lymphocytic leukemia.&#x0D; To diagnose Merkel cell carcinoma, five criteria of the AEIOU algorithm proposed in 2008 by a group of scientists at the University of Washington are used.&#x0D; From the methods of laboratory diagnostics a detailed analysis of blood is used, also a histological and immunohistochemical study is carried out . Among the methods of instrumental diagnostics, ultrasound examination of the primary tumor and groups of lymph nodes of the appropriate localization, abdominal and pelvic organs; chest X-ray and skeletal bone scintigraphy; positron emission tomography combined with X-ray computed tomography are mandatory. A sentinel node biopsy followed by histological and immunohistochemical examination is recommended in the absence of metastatic lymph node lesions.&#x0D; We herein contribute by reporting a case of Merkel cell carcinoma affecting the forearm of a 51-year-old female. This clinical case confirms the aggressiveness of this type of the skin cancer as well as high possibility of misdiagnosis due to the scarce occurrence of Merkel cell carcinoma and lack of professional knowledge.&#x0D; Therefore, it is important for the practitioners involved in the care of skin lesions to be aware of this condition and the need for a multidisciplinary treatment approach.

EXPECT THE UNEXPECTED: A CASE OF VZV-INDUCED HYDRCEPALUS IN A PATIENT WITH RECURRENCE OF CLL

TYPE: Abstract TOPIC: Critical Care INTRODUCTION: Varicella-Zoster virus followed by herpes virus is the 2 most common viral causes of acute Encephalitis/Meningitis, especially in immunocompromised patients. Reactivation of VZV, after the primary chickenpox, generally presents as vesicular rash in one or more dermatomes, preceding or following the main manifestation. Neurological symptoms by VZV are well documented in the elderly, but it is rare to cause hydrocephalus. CASE PRESENTATION: A case of a 70-year-old male with a past medical history of Chronic Lymphocytic Leukemia about 23 years ago presented to the emergency department due to persistent nausea, vomiting, diarrhea, headache, and weakness for 5 days. After the first laboratory examination, a diagnosis of recurrence of CLL was made. He became increasingly lethargic and was started on Ceftriaxone, Azithromycin, and Acyclovir for suspicion of encephalitis. CSF PCR panel was positive for VZV and rhinovirus, negative for bands. He was intubated for airway protection. He underwent leukapheresis twice to reduce leukostasis. On Day 3 of the ICU stay, he remained obtunded, CT head revealed developing hydrocephalus, an external ventricular drain was placed. Repeat CSF revealed persistent positive VZV virus. Over the next few days, he remained comatose with no movements or improvement in neurological status and eventually passed away. DISCUSSION: Immunocompromised patients who have impaired T-cell mediated immunity are prone to viral encephalitis. This is the first reported case of VZV-induced hydrocephalus. CONCLUSIONS: It is important to raise awareness of the risk of VZV reactivation with severe neurological complications in patients with reactivation of malignancy. Acyclovir should be initiated early to prevent complications. DISCLOSURE: Nothing to declare. KEYWORD: VZV

Unusual Illustration of Richter Transformation in Chronic Lymphocytic Leukemia on FDG PET/CT.

A man with history of chronic lymphocytic leukemia (CLL) in remission had multiple rapidly growing lumps in recent 2 months. FDG PET/CT demonstrated disseminated FDG-avid nodal and extranodal lesions including those in unusual locations such as the nasopharynx, salivary glands, lungs, gastric wall, peritoneum, bones, and muscles. Subsequent biopsy of the right axillary mass showed absolute lymphocytosis with focus of large B-cell lymphoma. Flow cytometric immunophenotyping demonstrated κ-restricted CLL and B-cell lymphoma, consistent with Richter transformation of CLL. FDG PET/CT images of this case illustrated the most severe and most disseminated nodal and extranodal involvements of Richter transformation in CLL.

Incidence of Second Malignancies in the History of Chronic Lymphocytic Leukemia

IntroductionThe occurrence of other neoplasms in patients diagnosed with chronic lymphocytic leukemia (CLL) is a known but insufficiently studied complication, highlighting the need for further research.Our study aims to analyze the incidence of other malignancies in CLL.MethodsWe performed a retrospective observational study of patients diagnosed with CLL between 2000-2016 at our center.Variables collected included: demographics, stage at diagnosis, treatment, response to treatment, death, other neoplasm (type, date of diagnosis, outcome), biomarker profiles studied by karyotyping, FISH, immunoglobulin heavy chain gene variable region mutational status, and TP53 mutational status.A descriptive study was performed. Quantitative variables are described as medians with their range, and qualitative variables as percentages. The relationship between qualitative variables and the development of second malignancies was performed using Chi-square and Fisher's exact test. Survival analyses were performed using the Kaplan-Meier method and the difference between groups was analyzed using the log-rank test.ResultsA total of 182 patients were evaluated, 104 men (57%) and 78 women (43%); median age: 74 years (39 - 97). Most patients were diagnosed at early stages (74% at Rai stage 0 and 84% at Binet stage A) and the median CIRS scale score at diagnosis was 4 (0 - 15).With a median follow-up of 76 months (20-212), 77/182 (42%) patients had received ≥1 line(s) of treatment: 1: 53%, 2: 26%, 3: 8%, ≥4: 13%.Forty-nine cases (27%) were reported with other malignancies in addition to CLL; cases with Richter transformation (n=5, 2.7%) were excluded.The diagnosis of CLL preceded the other neoplasm in 33/182 cases (18%): 8 hematologic and 27 non-hematologic neoplasms. Half of the hematologic malignancies involved MGUS (n=4), 1 mutated JAK2 (V617F) cMPN, 1 AML and 1 MALT lymphoma. As for non-hematologic tumors, non-melanoma skin cancer accounted for 30% of cases (n=8), followed by breast cancer (n=5, 18.5%). Neoplasms of the stomach, colon, liver, bladder and prostate together accounted for 37%, in the same proportion each (n=2, 7.4%). The remaining neoplasms corresponded to lung and bronchus, kidney, melanoma and pancreas. Five of the 27 patients had a third solid organ neoplasm, with non-melanoma skin cancer again being the most frequent (n=2). The other neoplasms were lung, small bowel and thyroid.The incidence of second neoplasms was higher in treated patients (26% vs. 12.4%, p=0.019). The incidence of a second hematologic malignancy was related to treatment administration (9%) compared to 1% in untreated patients (p=0.011), especially in those with ≥ 3 lines (37.5% vs. 3%), p=0.024. We could not find any association between the variables analyzed and the development of second non-hematologic malignancies.The development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients.ConclusionsThe incidence of second malignancies is high in patients with CLL, being higher in those patients who have received treatment, and especially in those with a greater number of lines received. In contrast, the development of solid tumors did not seem to be affected by treatment administration, which should motivate further investigation in specific subgroups of patients. In our series, the development of second neoplasms after the diagnosis of CLL did not have a negative impact on the overall survival of these patients. DisclosuresGonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

Differential Levels of mRNAs in Normal B Lymphocytes, Monoclonal B Lymphocytosis and Chronic Lymphocytic Leukemia Cells from the Same Family Identify Susceptibility Genes.

IntroductionPeople with a family history of chronic lymphocytic leukemia (F-CLL) have an increased risk of monoclonal B lymphocytosis (F-MBL), which is found in up to 18% of first-degree relatives of patients compared to 5% of the total population. This may indicate that the presence of an F-MBL in the relative of a F-CLL patient is due to genetic susceptibility. In this study, we hypothesized that progressive changes in gene expression result in malignant transformation of B lymphocytes to F-MBL, and subsequent alterations in gene expression occur before overt F-CLL develops. The aim of this study of affected and unaffected individuals from a family with multiple CLL cases was to compare mRNA expression levels in control B-lymphocytes, pre-malignant F-MBL and malignant F-CLL cells.MethodsTo identify inherited changes in gene expression, a high-resolution DNA microarray was used to identify differentially abundant mRNAs in age-matched cases of F-MBL (n = 4), F-CLL (n = 2) and unaffected family relatives (F-Controls, n = 3) within one family. These were then compared to non-kindred controls (NK-Controls, n = 3) and sporadic CLL (S-CLL) cases (n = 6).ResultsSeven differentially abundant mRNAs were identified against similar genetic backgrounds of the family: GRASP and AC016745.3 were decreased in F-MBL and further decreased in F-CLL compared to F-Controls, whereas C11orf80 and METTL8 were progressively increased. PARP3 was increased in F-MBL compared to F-Controls but was decreased in F-CLL compared to F-MBL. Compared to F-Controls, levels of ROR1 and LEF1 were similarly increased in F-MBL and F-CLL. For six of the genes, there were no differences in mRNA levels between S-CLL and F-CLL; however PARP3 was higher in S-CLL.ConclusionThese results are consistent with the hypothesis that changes in expression of specific genes contribute to transformation from normal lymphocytes to MBL and CLL.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-021-00172-2.

S2768 An Uncommon Presentation of Elevated Liver Function Tests

Introduction: The most common causes of elevated liver function tests (LFTs) are nonalcoholic fatty liver disease and alcoholic liver disease. Uncommon causes include drug-induced liver injury, hepatitis B and C, and hereditary hemochromatosis. Rare causes include alpha1-antitrypsin deficiency, autoimmune hepatitis, and Wilson disease. Extrahepatic sources, such as thyroid disorders, celiac sprue, hemolysis, and muscle disorders, are also associated with mildly elevated transaminase levels. Case Description/Methods: A 61-year-old female with a history of Chronic lymphocytic leukemia (CLL) diagnosed in 2014 with confirmed remission for at least 7 years presented to the Hepatology clinic for evaluation of elevated LFTs. Extensive serological workup was negative. Ultrasound imaging showed hepatomegaly. Fibroscan showed K3 fibrosis kPa 10.3. MRI abdomen elastography showed liver fat fraction measures 16 %, consistent with mild steatosis (Figure 1). Liver elasticity measures 3.83 KPa consistent with F1 or F2 fibrosis. She underwent a liver biopsy which showed stage 3 fibrosis as well as chronic lymphocytic leukemia/small lymphocytic lymphoma predominantly CD20-positive B-cells. The B-cells are positive for CD5, CD23, BCL2 and LEF1, negative for CD10, BCL6, cyclin D1 and SOX11, the proliferation index (Ki-67) is low. CD3-positive reactive T-cells are seen. There was no morphologic evidence of large cell transformation. A multidisciplinary consensus was made to monitor her labs with no further treatment of her CLL at this time. Discussion: Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed leukemia in the U.S. Can involve different sites in the body including Spleen, and also Lymph nodes. Physicians should be aware of different uncommon presentations and sites of involvement that are possible in CLL. Here we presented a case of liver involvement to increase awareness.Figure 1.: The showed liver fat fraction measures 16 %, consistent with mild steatosis. Liver elasticity measures 3.83 KPa consistent with F1 or F2 fibrosis.

Testicular mass: a rare presentation of Richter's syndrome

BackgroundRichter’s syndrome is the transformation of indolent lymphoma into an aggressive form, most commonly diffuse large B cell lymphoma. Most patients are known to have chronic lymphocytic leukemia. Richter’s syndrome arises in the lymph nodes or bone marrow and rarely presents with extra nodal involvement.Case presentationOur patient presented with Richter’s syndrome at an extremely uncommon site, i.e., testis. This is the fourth case reported in literature. Moreover, our case represents the longest follow-up reported so far with recurrence-free survival of more than 2 years now.ConclusionTesticular mass in a patient with a history of chronic lymphocytic leukemia should raise the clinical suspicion of Richter’s syndrome and accordingly the patient should be thoroughly investigated and treated. Treatment needs multidisciplinary team approach: urologist, pathologist and hematologist.

CLL-333: New Era in the History of Chronic Lymphocytic Leukemia: Consequences of the Arrival of New Drugs

Context: In the last decade, the incorporation of anti-CD20 monoclonal antibodies, bendamustine, B-cell receptor inhibitors, and Bcl-2 antagonists have changed the paradigm of chronic lymphocytic leukemia (CLL) treatment, improving overall survival (OS). Objective: To evaluate the influence of the date of diagnosis (before or after 2010) and whether new drugs were received as frontline therapy. Design: We conducted a retrospective observational study. Patients or Other Participants: Patients diagnosed with CLL between 2003 and 2016. Interventions: No intervention was performed. Main Outcomes Measures: OS. Results: One hundred eighty-two patients were evaluated: 104 men (57%) and 78 women (43%); median age 74 years (39–97). Seventy-one patients (39%) were diagnosed before 2010, and 111 (61%) from 2010 onward. With a median follow-up of 76 months (range, 20–212), 77/182 (42%) patients had received ≥1 line(s) of treatment. Twenty patients (26%) received the front-line treatment before 2010. Half of the patients received new drugs in first-line (n=39), 92% of them from 2010 onward. Median OS of patients diagnosed before 2010 was 66 months (35.32–96.68) vs 143 months (95% CI 90.5–195.5) (p=0.032) as of 2010. In patients ≤ 65 years, median OS has not been reached, being 80.5% at 10 years: 65% for those diagnosed before 2010 and 97% after 2010, p=0.036. Median OS of patients > 65 years was 6 years (95% CI 4.17–7.83) and increased from 82 months for those diagnosed before 2010, to 110 months in those diagnosed after 2010, p=0.744. Patients treated with new drugs in first-line had an increased median OS from 76 months and 13% at 10 years to a median not reached and OS of 77% at 10 years, p=0.000. This difference was more prominent in those ≤ 65 years: 20% vs 100% at 10 years (p=0.012), while it was not significant for those > 65 years (11% vs 50% at 10 years, p=0.181). However, in a multivariate model, treatment with new drugs retained statistical significance (HR 0.414; 95% CI 0.183–0.935). Conclusions: The implementation of new drugs in the front line has led to an increase in OS, especially in young patients.

Poster: CLL-333: New Era in the History of Chronic Lymphocytic Leukemia: Consequences of the Arrival of New Drugs

Poster: CLL-333: New Era in the History of Chronic Lymphocytic Leukemia: Consequences of the Arrival of New Drugs

Posterior reversible encephalopathy syndrome in a patient with Richter's syndrome on combination DA-R-EPOCH chemotherapy regimen: a case report

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a clinical-radiologic entity characterized by headaches, altered mental status, seizures, visual loss, and a characteristic imaging pattern in brain magnetic resonance images. The exact etiology and pathogenesis of this condition are not yet fully elucidated.Case presentationA 72-year-old White man presented with 2 weeks of low-grade fever and chills, night sweats, fatigue, dysphagia, and new-onset rapidly increasing cervical lymphadenopathy. He had a history of chronic lymphocytic leukemia with transformation to diffuse large B-cell lymphoma for which he was started on dose-adjusted rituximab, etoposide, prednisone vincristine, cyclophosphamide, and doxorubicin (DA-R-EPOCH). Shortly after treatment initiation, the patient developed severe airway obstruction due to cervical lymphadenopathy that required emergency intubation. A few days later, the cervical lymphadenopathy and the status of the airway improved, and sedation was consequently weaned off to plan for extubation. However, the patient did not recover consciousness and developed generalized refractory seizures. Brain magnetic resonance imaging revealed edema in the cortical gray and subcortical white matter of the bilateral occipital and inferior temporal lobes, consistent with PRES.ConclusionsPosterior reversible encephalopathy syndrome refers to a neurological disorder and imaging entity characterized by subcortical vasogenic edema in patients who develop acute neurological signs and symptoms of a usually reversible nature in different settings, including chemotherapy. Despite its name, PRES is not always fully reversible, and permanent sequelae can persist in some patients. Clinicians should be aware of the possible association between chemotherapy and PRES to ensure early recognition and timely treatment.

The Clinicopathological Features of Epithelioid Undifferentiated Sarcoma with TFE3 Amplification with One Case Report

Herein, we first reported a case of undifferentiated sarcoma with epithelioid features harboring TFE3 amplification. A 66-year-old woman with a history of chronic lymphocytic leukemia and chemotherapy presented with a 4 cm palpable nodule in the left lower leg. Microscopically, the large epithelioid tumor cells with remarkable pleomorphism and the small round tumor cells intermingled with each other in a diffuse sheet or a hemangiopericytoma-like vascular growth pattern. Atypical mitotic figures and lymph node metastasis were found while tumor necrosis was absent. Immunohistochemically, the tumor was positive for vimentin, TFE3, and CD34. TFE3 gene amplification was identified by fluorescence in situ hybridization. The patient was alive and well without recurrence or metastasis for 12 months after tumor resection. The tumor should differentiate from PEComa, alveolar soft part sarcoma, epithelioid sarcoma, epithelioid angiosarcoma, and epithelioid rhabdomyosarcoma.