Madhu P. Menon

Isolated Ocular Manifestation of Relapsed Chronic Myelogenous Leukemia Presenting as Myeloid Blast Crisis in a Patient on Imatinib Therapy: A Case Report and Review of the Literature

Blast phase in chronic myelogenous leukemia (CML) has rarely been reported to involve extramedullary sites like skin, lymph nodes, and central nervous system. Clinical history, characteristic hematologic findings (elevated leukocyte counts, myelocytic predominance, and basophilia), and Philadelphia chromosome are of high diagnostic significance especially in isolated extramedullary presentations. We describe a unique case of CML relapse with blast phase involving the eye. A 66-year-old man with a known diagnosis of CML on imatinib and in molecular remission for 3 years presented with a painful blind eye. Histologic examination revealed diffuse involvement of choroid, iris, vitreous humor, and the optic nerve by blast cells. The blasts expressed CD34, aberrant TdT, and a myeloid phenotype (CD13, CD33, and CD117). Fluorescence in situ hybridization (FISH) of vitreous fluid detected BCR-ABL1 gene rearrangement. Additionally, trisomy 8 and gains of 9 and 22 were seen which were not present in the initial diagnostic marrow study 3 years ago. At relapse, the bone marrow, peripheral blood, and the cerebrospinal fluid were not involved by CML. Patient received induction chemotherapy and single dose prophylactic intrathecal methotrexate and was maintained on antityrosine kinase therapy and eventually underwent allogenic stem cell transplantation.

GATA3 Immunohistochemical Staining in Hodgkin Lymphoma: Diagnostic Utility in Differentiating Classic Hodgkin Lymphoma From Nodular Lymphocyte Predominant Hodgkin Lymphoma and Other Mimicking Entities

Background: Classic Hodgkin lymphoma (CHL) and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) are clinically distinct entities, with different prognostic and treatment implications. In addition, several large B-cell lymphomas and some T-cell lymphomas can mimic CHL. Differentiating these entities from CHL is crucial for ensuring appropriate therapy. GATA3 is a T-cell transcription factor involved in T-cell maturation and has been previously shown to be overexpressed in CHL cells via gene expression profiling. We investigated the utility of GATA3 immunostain in differentiating CHL from NLPHL and other mimicking entities. Materials and Methods: We accrued 17 NLPHLs, 49 CHLs [23 nodular sclerosis (NS), 3 syncytial variants, 3 lymphocyte rich and 13 mixed cellularity types], 4 primary mediastinal large B-cell lymphomas (PMBLs), 2 Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCLs) (EBV+LBCLs), 2 T-cell/histiocyte-rich large B-cell lymphomas (TCHRBCLs), 1 gray zone lymphoma, and 2 tissue microarrays consisting of 72 DLBCLs. One slide from each was stained with GATA3 and percent positive tumor cells and intensity of nuclear expression was semiquantitatively graded independently by 2 board certified hematopathologists. Results: GATA3 was positive in 80% of CHLs. Both percent positivity and intensity of staining varied greatly. Syncytial variant of NS subtype showed the highest positivity rate (3/3; 100%), followed by NS (20/23; 87%), mixed cellularity (9/13; 70%), and lymphocyte rich (2/3; 67%). GATA3 was negative in all NLPHLs, EBV+LBCLs, TCRBCLs, and DLBCLs stained. The single gray zone lymphoma and 3/4 PMBLs were positive. Conclusions: Nuclear expression of GATA3 can be used to delineate CHL from NLPHL. GATA3 positivity effectively excludes NLPHL with 100% negative predictive value. However, as 20% of CHL can be negative for GATA3, CHL cannot be ruled out with negative GATA3. Additional findings include GATA3 positivity among PMBLs, whereas all 72 DLBCLs were negative for GATA3. This finding further highlights similarities between CHL and PMBL.

Peripheral T-cell lymphomas of follicular helper T-cell type frequently display an aberrant CD3 −/dim CD4 + population by flow cytometry: an important clue to the diagnosis of a Hodgkin lymphoma mimic

Nodal follicular helper T-cell-derived lymphoproliferations (specifically the less common peripheral T-cell lymphomas of follicular type) exhibit a spectrum of histologic features that may mimic reactive hyperplasia or Hodgkin lymphoma. Even though angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma of follicular type share a common biologic origin from follicular helper T-cells and their morphology has been well characterized, flow cytometry of peripheral T-cell lymphomas of follicular type has not been widely discussed as a tool for identifying this reactive hyperplasia/Hodgkin lymphoma mimic. We identified 10 peripheral T-cell lymphomas of follicular type with available flow cytometry data from five different institutions, including two cases with peripheral blood evaluation. For comparison, we examined flow cytometry data for 8 classical Hodgkin lymphomas (including 1 lymphocyte-rich classical Hodgkin lymphoma), 15 nodular lymphocyte predominant Hodgkin lymphomas, 15 angioimmunoblastic T-cell lymphomas, and 26 reactive nodes. Lymph node histology and flow cytometry data were reviewed, specifically for the presence of a CD3−/dimCD4+ aberrant T-cell population (described in angioimmunoblastic T-cell lymphomas), besides other T-cell aberrancies. Nine of 10 (90%) peripheral T-cell lymphomas of follicular type showed a CD3−/dimCD4+ T-cell population constituting 29.3% (range 7.9–62%) of all lymphocytes. Five of 10 (50%) had nodular lymphocyte predominant Hodgkin lymphoma or lymphocyte-rich classical Hodgkin lymphoma-like morphology with scattered Hodgkin-like cells that expressed CD20, CD30, CD15, and MUM1. Three cases had a nodular growth pattern and three others exhibited a perifollicular growth pattern without Hodgkin-like cells. Epstein–Barr virus was positive in 1 of 10 cases (10%). PCR analysis showed clonal T-cell receptor gamma gene rearrangement in all 10 peripheral T-cell lymphomas of follicular type. By flow cytometry, 11 of 15 (73.3%) angioimmunoblastic T-cell lymphomas showed the CD3−/dimCD4+ population (mean: 19.5%, range: 3–71.8%). Using a threshold of 3% for CD3−/dimCD4+ T cells, all 15 nodular lymphocyte predominant Hodgkin lymphoma controls and 8 classical Hodgkin lymphomas were negative (Mann–Whitney P=0.01, F-PTCL vs Hodgkin lymphomas), as were 25 of 26 reactive lymph nodes. The high frequency of CD3−/dimCD4+ aberrant T cells is similar in angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas of follicular type, and is a useful feature in distinguishing peripheral T-cell lymphomas of follicular type from morphologic mimics such as reactive hyperplasia or Hodgkin lymphoma.

Post-transplant CD4+ non-cytotoxic γδ T cell lymphoma with lymph node involvement

Gamma delta T cells represent a minor subset of the normal lymphocyte component of the human immune system, largely inhabiting mucosal surfaces. Gamma delta T cell lymphomas (γδ TCLs) are thought to be derived from these cells and are rare, extremely aggressive lymphomas that typically exhibit a cytotoxic phenotype and often present in extranodal sites, most commonly as cutaneous or hepatosplenic subtypes. The immunophenotype usually lacks both CD4 and CD8 expression, but occasional cases express CD8. CD4 expression in γδ TCLs is exceedingly rare. The few reported cases tend to show a non-cytotoxic phenotype with preferential involvement of the lymph nodes. Cases showing cutaneous presentation or with an immunosuppressive clinical history, while relatively common among typical γδ TCLs, are even rarer among this unusual CD4+ subset. While this very small group appears to have an equally dismal prognosis to other types of γδ TCL, little else is known as to how they may differ biologically and whether they should be treated as a separate entity. We report a unique case of CD4-positive gamma delta T cell lymphoma with skin and systemic lymph node involvement in the post-transplant setting.

206 Expression of Estrogen Receptor Beta (ER[beta]) in Low Grade B-Cell Lymphomas: An Immunohistochemical Study

Introduction: Most lymphoid malignancies are associated with higher incidence and poorer prognosis in men than women. Epidemiological data associate reproductive hormones and oral contraceptives with reduced risk in women, attributed to estrogen. Estrogen’s action is mediated by two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), with different tissue distribution and actions. ERα promotes cell proliferation whereas ERβ shows antiproliferative effects. Studies show ERβ to be predominantly expressed in lymphoid tissue. There is a dearth of studies about expression of ERβ in lymphoid malignancies. Hence, we characterized the expression of ERβ in low grade Bcell lymphomas by immunohistochemistry in men and women. Methods and Materials: Low-grade B-cell lymphomas diagnosed between 2006 and 2016 were retrieved from archives. ERβ immunostaining was performed on formalin-fixed paraffin-embedded sections of 45 lymphoma cases with typical histology, flow cytometry, and cytogenetics: 10 chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (six men, four women), nine mantle cell lymphomas (five men, four women), 10 marginal zone lymphomas (four men, six women), eight follicular lymphomas (four men, four women), four classical (two men, two women), and four nodular lymphocyte predominant (two men, two women) Hodgkin lymphomas. Control tissue from tonsils, lymph nodes, and spleen were also immunostained. Results: Immunohistochemical ERβ staining of tonsils and lymph nodes in men and women show strong nuclear staining of lymphocytes in the germinal and mantle zone of the lymphoid follicles as compared to the paracortical region. The white pulp (periarteriolar lymphatic sheath) and red pulp in spleen show strong ERβ positivity. Strong nuclear staining of lymphocytes was seen in all cases of CLL/SLL, mantle, marginal, follicular, and Hodgkin lymphomas. No difference in staining was seen between men and women in normal lymphoid and lymphoma specimens. Conclusion: All low-grade Bcell lymphomas strongly express ERβ in men and women, highlighting role of estrogens in pathogenesis. Since estrogen concentrations are higher in women, this might explain the sex predilection and poorer prognosis in men. Also, these results raise the possibility of using ERβ agonists as a novel therapeutic agent in these lymphomas.

Plasmacytoid lymphocytes: a clue to dengue diagnosis

![Figure][1] A 36-year-old man presented with fever, myalgia, and fatigue after a trip to India. Laboratory studies revealed a white blood cell count of 2.8 × 109/L, hematocrit of 40.1%, platelet count of 18 × 109/L, abnormal liver function tests, elevated fibrin degradation products, and