Primary CNS T-cell Lymphomas: A Clinical, Morphologic, Immunophenotypic, and Molecular Analysis.

Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs.

NOTCH1 intracellular domain immunohistochemistry as a diagnostic tool to distinguish T-lymphoblastic lymphoma from thymoma.

Distinction between lymphocyte-rich thymoma and T-lymphoblastic lymphoma/leukemia (T-LBL) can be problematic because of a predominance of precursor T cells in both, particularly if the epithelial component in a thymoma is undersampled. Because of very different clinical implications, accurate diagnosis is critical. The NOTCH1 signaling pathway is frequently activated in T-LBL and plays a central role in the pathogenesis of this disease.

Frequency, interobserver reproducibility and clinical significance of equivocal peaks in PCR clonality testing using Euroclonality/BIOMED-2 primers.

Aims: PCR studies for lymphoid clonality are now widely employed, especially using Euroclonality/BIOMED-2 primers. Criteria for interpretation as a clonal result, however, have proven controversial. This study examines the frequency and clinical significance of equivocal amplification patterns and measures the interobserver reproducibility of clonality interpretations.

Solitary extramedullary plasmacytoma of the penis.

Solitary extramedullary plasmacytomas are rare plasma cell malignancies, particularly outside the upper aerodigestive tract. A 90-year-old male presented with a penile mass suspicious for penile carcinoma. Pathology revealed the tumor to be an Epstein-Barr virus-associated plasmacytoma with no radiographic evidence of bone or other soft tissue involvement.

Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma.

Follicular lymphoma (FL), a common lymphoma in adults, occurs rarely in pediatric and young adult patients. Most pediatric cases have been described as grade 3, but the criteria to distinguish the pediatric variant of FL (PFL) from usual FL (UFL) seen in adults are not well defined. We undertook a study of FL in patients under the age of 30.

Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma.

Follicular lymphoma in situ (FLIS) was first described nearly a decade ago, but its clinical significance remains uncertain. We reevaluated our original series and more recently diagnosed cases to develop criteria for the distinction of FLIS from partial involvement by follicular lymphoma (PFL). A total of 34 cases of FLIS were identified, most often as an incidental finding in a reactive lymph node.

Spontaneous perinephric hematoma due to acquired factor X deficiency in AL amyloidosis.

Spontaneous perinephric hematoma (SPH) is a rare entity whose diagnosis is challenging because of its varied clinical presentation and lack of any specific etiology. We report a 34-year-old African-American male who presented with left flank pain and was found to have a large left perinephric hematoma, in the setting of undiagnosed AL amylodosis. The case illustrates that while a SPH due to the vascular angiopathy of amyloid is rare, when amyloidosis is associated with abnormal coagulation studies or bleeding at multiple sites, it should be considered because of its protean systemic manifestations and potential response to chemotherapy.

Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications.

Background: Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited.

Design And Methods: This retrospective study analyzed the pathological and clinical findings of nine cases of blastic plasmacytoid dendritic cell neoplasm presenting in patients under the age of 18 years who were reviewed at our institution. We also identified 20 well-documented additional pediatric cases in the literature.

Plasmacytoid dendritic cells: physiologic roles and pathologic states.

Plasmacytoid dendritic cells (PDCs) have perplexed pathologists for decades, undergoing multiple adjustments in nomenclature as their lineage and functions have been characterized. Although PDCs account for less than 0.1% of peripheral blood mononuclear cells, they serve as a principal source of interferon-alpha and are also known as interferon-I producing cells (IPCs).

Galectin-3 induces death of Candida species expressing specific beta-1,2-linked mannans.

Lectins play a critical role in host protection against infection. The galectin family of lectins recognizes saccharide ligands on a variety of microbial pathogens, including viruses, bacteria, and parasites. Galectin-3, a galectin expressed by macrophages, dendritic cells, and epithelial cells, binds bacterial and parasitic pathogens including Leishmania major, Trypanosoma cruzi, and Neisseria gonorrhoeae.

Differential roles of SOCS family members in EpoR signal transduction.

To elucidate the roles of suppressor of cytokine signaling (SOCS) family members in erythropoietin (EPO) signaling, we explored SOCS gene regulation, mRNA stability, and protein function in two EPO-responsive hematopoietic cell lines. Using two independent approaches, one involving inhibition of specific signaling molecules and the other employing cell lines that express particular EpoR mutants and thereby activate only subsets of signaling cascades, we demonstrate that induction of SOCS1, SOCS2, SOCS3, and cytokine-inducible SH2-containing protein (CIS) in response to EPO stimulation appears to depend on Stat5 but not on mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K). SOCS4 expression, in contrast, does not appear to be EPO inducible.

Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis.

In the search for genes expressed in hematopoietic stem cells, we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes. Gfi-1 and Gfi-1B are zinc finger proteins that share highly conserved SNAG and 6 zinc finger domains. Gfi-1 has been characterized as an oncogene involved in lymphoid malignancies in mice.

Erythropoietin receptor haploinsufficiency and in vivo interplay with granulocyte-macrophage colony-stimulating factor and interleukin 3.

Erythropoietin (EPO) and its receptor (EPOR) are critical for definitive erythropoiesis, as mice lacking either gene product die during embryogenesis with severe anemia. Here we demonstrate that mice expressing just one functional allele of the EpoR have lower hematocrits and die more frequently than do wild-type littermates on anemia induction. Furthermore, EpoR(+/-) erythroid colony-forming unit (CFU-E) progenitors are reduced both in frequency and in responsiveness to EPO stimulation.

Regulation of Socs gene expression by the proto-oncoprotein GFI-1B: two routes for STAT5 target gene induction by erythropoietin.

SOCS proteins take part in a classical negative feedback loop to attenuate cytokine signaling. Although STAT family members positively modulate Socs gene expression, little else is known about Socs gene regulation. Here, we identify functional binding sites for GFI-1B, a proto-oncogenic transcriptional repressor, in the promoters of murine Socs1 and Socs3.