Multifocal Follicular Lymphoma Isolated to the Gastrointestinal Tract: A Rare Finding.

Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma. Although extranodal involvement of the gastrointestinal (GI) tract is common in lymphomas, primary GI-FL confined to the GI tract is relatively rare. The disease process is typically indolent in nature and usually incidentally found. Among this subset of patients, the duodenum and terminal ileum tend to be the most common site of origin. Here, we present a rare case of primary multifocal GI-FL that found incidentally during routine colonoscopy with subsequent esophagogastroduodenoscopy and video capsule endoscopy revealing duodenal, jejunal, and sigmoid colon involvement.

Small Cell Carcinoma of the Rectum-An Unexpected Diagnosis: Current Treatment Options for a Rare and Aggressive Entity.

Rectal small cell carcinoma is a rare and aggressive cancer subtype for which a consensus of optimal treatment has not yet been reached. This cancer presents a difficult surgical problem, and thus, the mainstay of treatment tends to mirror that of small cell carcinoma of the lung (chemotherapy, radiation therapy, and immune modulators). This brief report highlights current treatment options available for this rare and difficult entity. There is a significant need for large-center clinical trials and prospective studies to help determine the best treatment regimen to effectively care for patients with small cell carcinoma of the rectum.

Encephalitis associated with a monoclonal protein band present in blood, urine and cerebrospinal fluid.

Introduction: Monoclonal protein bands are present mainly in blood and secondary in urine representing specific antibody produced in excess by abnormal lymphocytes or plasma cells.We describe a case of a patient with acute encephalitis associated with an unexpected finding of a monoclonal protein band present in blood, urine and in cerebrospinal fluid (CSF). Case presentation: This 50-year-old woman with no significant past medical history, with the exception of unintentional weight loss exceeding 5 kg over the last 3 months, presented to the emergency department with seizures and altered mental status, after 3 days of vomiting and headaches. Magnetic Resonance Imaging showed lesions suspicious for infectious encephalitis/meningitis and for ischemia possibly related to central nervous system (CNS) autoimmune vasculopathy/vasculitis. The patient died the following day after losing brainstem reflexes. Testing for the previously mentioned etiologies returned negative with the exception of high protein concentration and increased immunoglobulin gamma (IgG) concentration in the CSF. Protein electrophoresis, ordered in error, showed a well-defined IgG with lambda light chain monoclonal protein band running in similar positions in serum, urine and in CSF. Due to SARS-CoV-2 PCR positivity no autopsy was performed. Conclusion: The presence of this monoclonal protein band produced in the CNS suggests the diagnosis of CNS myeloma. The accelerated course in this case could be the result of the CNS myeloma or lymphoma responding to SARS-CoV-2 infection. Testing for monoclonal protein bands in CSF, in patients with pertinent clinical presentation would boost the awareness of this these diseases improving patient care.

Merkel cell carcinoma brain metastasis with radiological findings mimicking primary CNS lymphoma: illustrative case.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor with a high likelihood of distant metastasis. Approximately 30 cases of MCC brain metastasis have been reported. The authors report a case of MCC brain metastasis with imaging findings mimicking primary central nervous system lymphoma. OBSERVATIONS: A 69-year-old asymptomatic White female with a past medical history of rheumatoid arthritis and MCC of the right cheek with no known regional or distant spread presented with a right frontal lobe lesion discovered incidentally on a surveillance scan. Brain magnetic resonance imaging revealed a vividly enhancing homogeneous lesion with restricted diffusion on diffusion-weighted imaging and corresponding apparent diffusion coefficient maps. Imaging characteristics suggested a highly cellular mass consistent with primary central nervous system lymphoma; however, given the likelihood of metastasis, resection was recommended. An intraoperative frozen section suggested lymphoma. However, further examination revealed positive cytokeratin 20 staining for a tumor, and a final diagnosis of MCC brain metastasis was made. LESSONS: Imaging characteristics of MCC brain metastasis can vary widely. A high level of suspicion should be maintained in a patient with a known history of MCC. Aggressive resection is recommended, regardless of appearance on scans or pathology of frozen sections, because MCC can mimic other intracranial pathologies.

CD30+ Lymphoproliferative Disorders as Potential Candidates for CD30-Targeted Therapies.

CONTEXT.­: In the early 1980s, a monoclonal antibody termed Ki-1 was developed against a cell line derived from a patient with Hodgkin lymphoma. This antibody detected a limited number of benign activated lymphocytes in lymphoid tissue, whereas in Hodgkin lymphoma it appeared to be nearly specific for Reed-Sternberg cells and their mononuclear variants. Subsequent studies showed that Ki-1 expression defined a new type of lymphoma that was later designated anaplastic large cell lymphoma with or without anaplastic large cell kinase expression/translocation. In the past 30 years, numerous new lymphoma entities have been defined, many of which are variably positive for CD30. Many virally transformed lymphoproliferative disorders are also frequently positive for CD30. OBJECTIVE.­: To illustrate the broad spectrum of CD30+ hematologic malignancies and to provide an update of CD30-targeted therapies. DATA SOURCES.­: Personal experiences and published works in PubMed. CONCLUSIONS.­: Because of its low expression in normal tissue, CD30 was studied as a therapeutic target for many years. However, the first functional humanized antibody against CD30 was developed only about 10 years ago. Brentuximab vedotin is a humanized anti-CD30 antibody linked to a cytotoxin, and was approved by the US Food and Drug Administration in 2012 for treating refractory Hodgkin lymphoma and anaplastic large cell lymphoma. Since then, the list of Food and Drug Administration-approved CD30-targeted hematologic malignancies has grown. Recently, the therapies using tumor antigen-specific chimeric antigen receptor T cells targeting CD30 have incited a great deal of enthusiasm and are studied in clinical trials.

Malignant pleural neoplasm with both differentiation of epithelioid mesothelioma and squamous-cell carcinoma, a rare phenomena.

Malignant mesothelioma, a neoplasm arising within the serosal surfaces, has been linked closely to asbestos exposure. We present a case of 72-year-old male with a 27 year work-related history of asbestos exposure who presented with dyspnea. Chest computed tomography scan showed a large, right pleural effusion with compressive right lung atelectasis. Biopsies, subsequent pleurectomy and lung wedge resections revealed epithelioid malignant mesothelioma with associated focal non-keratinizing squamous-cell carcinoma, supported by extensive immunohistochemical stains and molecular studies. The patient was treated with 6 cycles of carboplatin/pemetrexed, showing no new metastases. Seven months post-treatment, the patient presented with progressive dyspnea and large pleural effusions. Bilateral pleural fluid was collected and showed malignant epithelioid cells, morphologically similar to the patient's pleural neoplastic cells. However, the tumor was positive for squamous cells markers and showed BAP1 loss, while negative for mesothelial markers. The findings support the diagnosis of squamous-cell carcinoma and were consistent with the patient's previously diagnosed pleural neoplastic origin. A malignant mesothelioma associated with squamous-cell carcinoma is a rare phenonmenon. To our knowledge, only two case reports are available in current literature. This unique case shows a single pleura tumor differentiating as both malignant mesothelioma and squamous-cell carcinoma. Squamous-cell carcinoma is the predominating malignancy seen within the bilateral pleural effusions, a potential pitfall for cytology specimen diagnosis.

Personal Control Over Decisions to Participate in Research by Persons With Histories of Both Substance Use Disorders and Criminal Justice Supervision.

Individuals must feel free to exert personal control over decisions regarding research participation. We present an examination of participants' perceived personal control over, as well as reported pressures and threats from others, influencing their decision to join a study assessing the effectiveness of extended-release naltrexone in preventing opioid dependence relapse. Most participants endorsed a strong sense of control over the decision; few reported pressures or threats. Although few in number, participants' brief narrative descriptions of the pressures and threats are illuminating and provide context for their perceptions of personal control. Based on this work, we propose a useful set of tools to help ascertain participants' sense of personal control in joining research.

Assessing informed consent in an opioid relapse prevention study with adults under current or recent criminal justice supervision.

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.

Childhood de novo CD5+ Diffuse Large B-cell Lymphoma: a Separate Entity?

De novo CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) is a subtype of DLBCL found predominantly in older individuals. This particular subtype has been associated with a female predominance and a more aggressive clinical course. Conversely, this entity has not been described in the pediatric population. We report a case of a 12 year-old boy who presented with an ileocecal intussusception. Radiologic, morphologic, and immunophenotypic analysis revealed an isolated extranodal mass consistent with a CD5+ DLBCL, germinal center cell phenotype. Fluorescent in situ hybridization analysis was negative for cMYC, BCL6, BCL2, MLL, and IGH/CCND1 rearrangement and showed loss of one copy of MLL in 32% cells. The patient was treated with four cycles of cyclophosphamide, vincristine, prednisolone, methotrexate, and doxorubicin and achieved complete remission. To the best of our knowledge, this is the first detailed report of a de novo CD5+ DLBCL occurring in a child.

MYC protein expression in primary diffuse large B-cell lymphoma of the central nervous system.

Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (≥ 40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology.

C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance?

C-myc protein expression has been studied in mature B-cell lymphomas and overexpression has been associated with poor prognosis. We sought to determine the prognostic significance of c-myc protein expression in B-ALL. We found ≥ 20% c-myc expression to predict risk of persistent disease in all age groups (odds ratio 7.487, p=0.013). There was no statistically significant association between c-myc expression and risk of relapse or death in our study. Routine c-myc immunostaining may help identify higher risk patients and guide management of B-ALL. Additional studies are needed to further determine the molecular mechanisms and role of c-myc expression in B-ALL.

Early T-cell precursor leukemia/lymphoma in adults and children.

Early T-cell precursor-ALL (ETP-ALL) is a subtype of T-ALL with a poor prognosis in children. We analyzed ETP-ALL compared to conventional T-ALL/LBL in both adults and children to determine any differences in clinical outcomes, based on the following parameters: induction failure, relapse, and survival. Patients with ETP-ALL have a higher risk of relapse, especially in children (in all patients, HR=4.08, p=0.127, and children, HR=11.63, p=0.025). ETP-ALL seems to have an increased risk of adverse outcomes, particularly in children. Larger studies are needed to better determine the prognosis of this subtype of T-ALL.