Volume 2, Issue 1, March 2017

Opinions

Gene, Life, and Disease – A Node Theory Page 1-13
X. Frank Zhao
Abstract

The 21st century embraces a combination of the Genomic and Information Ages, characterized by enormous genetic data deposition and use of numerous powerful analytical tools. With more and more accumulated data, the concept of genes needs to be redefined and research methods further rationalized based on the properties of life: economy, optimization and survival. Disease should be considered the condition where homeostasis is disrupted. Biological equilibrium is maintained by a network of numerous functional nodes: molecules located in various pathways that are classified into decision nodes and alternative nodes, which shift their roles in response to a changing environment. Organized both spatially and temporally, the nodal network carries out its functions for the optimal outcome of the cell. Although central nodes often play vital roles for cell functions, connector nodes in the “structural hole” are more effective targets for treatment. Resources should be prioritized to delineate the roles of functional nodes and identify critical nodes for optimal therapy.

Case Report

Diagnostic challenge: Acute leukemia with biphenotypic blasts and BCR-ABL1 translocation Page 14-18
Ling Wang and Xiangdong Xu
Abstract

Chronic myelogenous leukemia (CML) and mixed phenotype acute leukemia (MPAL) are two distinct entities according to the current WHO classification. However, the distinction can be difficult when adequate clinical history is not available, because both entities could have BCR-ABL1 translocation and B/myeloid biphenotypic blasts. Here we report a 64-year-old man with no previous history of myeloproliferative disorders who presented with marked leukocytosis and 30% circulating blasts. The bone marrow had 39% of blasts and 32% maturing myeloid cells. The blast population showed both B and myeloid differentiation. Cytogenetics revealed the BCR-ABL1 translocation as the sole abnormality. Based on one small-sized case series, many features of our case favored the diagnosis of CML in blast phase with biphenotypic blasts, including: 1) left-shifted granulocytic maturation in peripheral blood; 2) a significant portion of maturing myeloid cells in bone marrow; 3) the diagnostic marrow with higher percentage of BCR-ABL1 harboring cells than that of the blasts; 4) BCR-ABL1 translocation as the sole cytogenetic abnormality; 5) post-induction marrow showed hypercellularity.

Case Report

CD20-positive primary cutaneous extranodal NK/T-cell lymphoma Page 19-23
Xiangdong Xu, Laura Romero, Young Kim, and X. Frank Zhao
Abstract

Cutaneous extranodal NK/T-cell lymphoma, nasal type, and primary cutaneous g/d T-cell lymphoma (PCGD-TCL) are rare cutaneous lymphoid neoplasms with overlapping features. Although EBV positivity favors the former, EBV+ PCGD-TCL has recently been reported. They also share cytotoxic markers and a poor prognosis. Here we report an unusual case of cutaneous NK/T-cell lymphoma with overlapping features of PCGD-TCL in a 55-year-old man who also developed hemophagocytic lymphohistiocytosis. Although it presents the typical pathological and immunophenotypic features of a cutaneous NK/T-cell lymphoma and PCGD-TCL, it aberrantly expresses CD20, giving an impression of mixed populations of T cells and B cells that are commonly seen in reactive conditions. This rare case represents a diagnostic pitfall and intends to raise more awareness among both pathologists and dermatologists. The CD20 positivity may also provide a target for rituximab therapy.

Case Report

Transient monosomy 7 associated with bicytopenia in a 9-month-old boy: Report of a case and review of the literature Page 24-30
Guang Yang, Ross A. Rowsey, Jun Wang, Rhett P. Ketterling, and Ross Fisher
Abstract

Monosomy 7 or partial loss in the long arm of this chromosome is a recurrent nonrandom
cytogenetic finding associated with a variety of hematological disorders. In the present case, a 9-month-old male presented with a febrile illness along with anemia and thrombocytopenia, and achieved spontaneous remission of the bicytopenia and monosomy 7 without any intervention 28 months after initial diagnosis. To our knowledge and literature search, this is likely the first case report of transient monosomy 7 in a patient with only bicytopenia. It is critical to closely monitor patients with monosomy 7 for evidence of spontaneous remission before proceeding to any major treatment.

Article

Unusual variants of mantle cell lymphoma Page 31-49
Stefano Fratoni
Abstract

Mantle cell lymphoma (MCL) is recognized as an aggressive and incurable small B-cell lymphoma
and represents a group of t(11;14)(q13;q32)/CCND1+ neoplasms with a wide variety of morphology. Thus, the identification of various MCL variants is important for guiding appropriate therapies and predicting outcomes. Histopathologic diagnosis of classical MCL is usually straightforward due to its typical morphology and nuclear overexpression of cyclin D1. However, approximately 10% of the MCL are represented by its own morphologic variants, mimicking other lymphomas, including the challenging cyclin D1-negative MCL. Furthermore, typical MCL immunophenotype and genetic abnormalities may not be found in every case. Therefore, MCL variants may be a diagnostic trap for hematopathologists. Taking into account that histopathological diagnosis remains the gold standard for MCL diagnosis, this paper summarizes the practical approaches to the diagnosis of the uncommon variants of MCL in accordance with the 2016 revised WHO classification of lymphoid neoplasms.

Case Report

Unusual extranodal composite CD5 negative mantle cell lymphoma and CD5 positive marginal zone lymphoma Page 50-57
Jiong Yan and Yue Wu
Abstract

Composite lymphomas composed of two non-Hodgkin small B cell lymphomas are infrequent and composite mantle cell lymphoma and marginal zone lymphoma is extremely rare with 3 cases reported to date. The case presented herein is the first report of extranodal composite CD5 negative mantle cell lymphoma and partially CD5 positive marginal zone lymphoma. The identification of these two histologically indistinct and immunophenotypically unconventional lymphoma components requires a comprehensive study including careful interpretation of immunohistochemical results and the fluorescence in-situ hybridization (FISH) analysis of t(11;14). Clinically, the diagnosis of this composite lymphoma is compatible with patient’s aggressive disease course. Molecular studies for immunoglobulin gene rearrangement indicate that the mantle cell lymphoma and marginal zone lymphoma components are derived from different clones, supporting the notion that composite lymphomas of non-Hodgkin small B cell lymphomas are often biclonal.

Article

PD-L1 protein expression in most EBV-driven lymphoproliferative disorders is not associated with 9p24.1 amplification Page 58-68
Alan F. Brown, Mohamad E. Salama, Jay L. Patel, Christian N. Paxton, Xinjie Xu, Sherrie L. Perkins, and K. David Li
Abstract

Programmed Cell Death 1 Ligand 1 (PD-L1) protein expression by tumor cells appears to mediate immune evasion and can be upregulated by 9p24.1 amplification. Alternatively, PD-L1 expression has been linked to EBV-driven activation of the AP-1 and MAPK pathways in EBV-positive Hodgkin lymphoma. We sought to evaluate the status of 9p24.1 with respect to PD-L1 expression in EBV-driven lymphoproliferative disorders (EBV+ LPDs).
We studied 36 LPDs (8 EBV+ diffuse large B-cell lymphoma (DLBCL), 10 DLBCL, NOS, and 18 others) using two PD-L1 immunohistochemical (IHC) stains and performed genome-wide copy number variation analysis on a subset of cases. Most cases of EBV+ DLBCL (5/8, 63%) showed PD-L1 expression by IHC and had normal copy number at 9p24.1 (7/8; 88%). One case of EBV+ DLBCL expressed PD-L1 with concurrent 9p24.1 amplification. A subset of EBV-negative DLBCLs showed PD-L1 expression without 9p24.1 amplification. Additionally, EBV+ LPDs displayed significantly lower total genomic aberrations and deletion 6q compared with EBV-negative cases.
PD-L1 expression in most EBV+ DLBCL cases is not due to 9p24.1 amplification. EBV infection appears to coincide with PD-L1 expression, supporting the model for EBV-driven PD-L1 upregulation. PD-L1 expression was seen in some cases lacking both EBV and 9p24.1 amplification, suggesting additional pathway(s) of activation.

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