Background: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases.
View Article and Find Full Text PDFThe molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral or calvarial bone marrow and meninges, bypassing the blood-brain barrier. This process is dependent on BCC engagement with vascular basement membrane laminin through expression of the neuronal pathfinding molecule integrin α6.
View Article and Find Full Text PDFBackground: Ki-67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki-67 expression and survival outcomes in MM in the era of novel therapies.
View Article and Find Full Text PDFA wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understood. In this paper, we present a multiple instance learning-based approach to aggregate high-resolution morphological information across many blood cells and cell types to automatically diagnose disease at a per-patient level.
View Article and Find Full Text PDFThere is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we present a case of Wolman disease presenting as hepatosplenomegaly in an infant.
View Article and Find Full Text PDFDermatophytosis incognito can be missed in diagnosis, given its relatively low prevalence as compared with common cases of dermatophytosis and therefore, is likely under-reported. Cutaneous T-cell lymphoma (CTCL) is also a rare entity with variable clinical manifestations. While successful treatment of dermatophytosis is feasible withmultiple topical and systemic antifungal options, CTCL can present a therapeutic challenge associated with significant emotional distress for the patients.
View Article and Find Full Text PDFBackground: Clonal immunoglobulin and T-cell receptor rearrangements serve as tumor-specific markers that have become mainstays of the diagnosis and monitoring of lymphoid malignancy. Next-generation sequencing (NGS) techniques targeting these loci have been successfully applied to lymphoblastic leukemia and multiple myeloma for minimal residual disease detection. However, adoption of NGS for primary diagnosis remains limited.
View Article and Find Full Text PDFPurpose: Diagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity between a working diagnosis of PMBCL at our institution and the clinicopathologic criteria established within the 2017 World Health Organization (WHO) classification.
Patients And Methods: Medical records and archived tissue of patients treated for stage I-II PMBCL from 1998 to 2018 were retrospectively reviewed for clinical and pathologic conformity with current WHO criteria.
The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic review, FISH, SNP-microarray, and next-generation sequencing of 16 cases of dFL. We found unique morphologic features, including interstitial sclerosis, microfollicle formation, and rounded nuclear cytology, confirmed absence of t(14;18) and recurrent deletion of 1p36, and showed a novel association with deletion/CN-LOH of 16p13 (inclusive of CREBBP, CIITA, and SOCS1).
View Article and Find Full Text PDFHematolymphoid neoplasms, including lymphoma and myeloid neoplasms, can occur in patients with sickle cell disease (SCD) or equivalent hemoglobinopathy, but an underlying connection between the two conditions has yet to be fully determined. Herein, we report a unique case of sequential development of two separate hematolymphoid neoplasms, human herpes virus 8 (HHV8)-positive diffuse large B-cell lymphoma (DLBCL) and chronic myelomonocytic leukemia, in a 59 year-old African American female with hemoglobin SC disease. While etiology of immunodeficiency is unknown, the potential causes include hydroxyurea therapy, disease related immunomodulation, chronic inflammation, and relatively old age.
View Article and Find Full Text PDFMyeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35.
View Article and Find Full Text PDFPurpose: Myelodysplastic syndrome (MDS) is associated with a dysregulated innate immune system. The purpose of this study was to determine whether modulation of the innate immune system via high mobility group box-1 (HMGB1) could reduce cell viability in MDS.
Experimental Design: We quantified HMGB1 in an MDS cell line MDS-L and in primary MDS cells compared with nonmalignant hematopoietic cells.
Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of influencing cellular commitment to apoptosis, using sensitization to the BCL-2 inhibitor ABT-199 in BCL-2-dependent acute myeloid leukemia (AML) cell lines as a proxy for apoptotic disposition. This analysis revealed metabolic pathways that specifically cooperate with BCL-2 to sustain survival.
View Article and Find Full Text PDFPurpose: To report a case of extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type metastatic to the space beneath the retinal pigment epithelium (RPE) with coincident paraneoplastic lymphoma-associated retinopathy.
Methods: Findings of clinical and histopathologic examination are presented with differential diagnoses and a literature review.
Case Report: A 53-year-old man presented with bilateral blindness and had exudative retinal detachments overlying subretinal masses in both eyes.
Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined.
View Article and Find Full Text PDFObjectives: Therapy-related chronic myeloid leukemia (CML) has been reported, but its clinical presentation and pathologic features have not yet been well characterized.
Methods: Twenty-one cases of CML following treatment for primary diseases were collected and retrospectively analyzed.
Results: The clinical presentation, pathologic features, and cytogenetic profile were similar to de novo CML.
Recent evidence has implicated in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between and the previously known causative gene accounting for the similarity in clinical features. Relatively little is known about the phenotypes associated with pathogenic variants in the gene, but the initial indication was that phenotypes may be more severe, when compared with SDS. We report a pediatric patient who presented with a metaphyseal dysplasia and was found to have biallelic variants in on reanalysis of trio whole-exome sequencing data.
View Article and Find Full Text PDFTraditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders.
View Article and Find Full Text PDFPurpose: To describe the ophthalmic symptoms and histopathological findings in a case of primary neurolymphomatosis (NL).
Observations: A man in his 60s with a prior diagnosis of chronic inflammatory demyelinating polyneuropathy developed facial numbness, diplopia, drooling, and difficulty swallowing. Over a 3-month period, he developed total ptosis and ophthalmoplegia of the right eye with a dilated, non-reactive pupil considered secondary to cranial nerve III and VI palsies.
Objectives: Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML).
Methods: Retrospective review of clinical and laboratory data.
Open Forum Infect Dis
September 2016
We report the case of a 60-year-old man with septic shock due to that was diagnosed in 24 hours by a novel whole-genome next-generation sequencing assay. This technology shows great promise in identifying fastidious pathogens, and, if validated, it has profound implications for infectious disease diagnosis.
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