Rare T-Cell Subtypes.

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.

Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions.

CD30 is a member of the tumor necrosis factor receptor superfamily. It is characteristically expressed in certain hematopoietic malignancies, including anaplastic large cell lymphoma and Hodgkin lymphoma, among others. The variable expression of CD30 on both normal and malignant lymphoid cells has focused research efforts on understanding the pathogenesis of CD30 upregulation, its contribution to lymphomagenesis through anti-apoptotic mechanisms, and its effect on cell survival. Given the restriction of CD30 to certain tumor types, the logical extension of this has been to attempt to exploit it as a therapeutic target. The efficacy of naked anti-CD30 antibodies in practice was, however, modest. Moreover, combinations with bacterial toxins and radioimmunoconjugates have also had limited success. The development of the antibody-drug compound brentuximab vedotin (BV), however, has rejuvenated interest in CD30 as a tumor target. Phase I and II clinical trials in Hodgkin lymphoma, peripheral T-cell lymphoma, cutaneous T cell lymphoma, and even CD30-expressing B-cell lymphomas, have shown the compound is well tolerated, but more importantly, able to deliver meaningful disease control even in patients with multiply relapsed or refractory disease. FDA approval has been granted for its use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. A recent phase III trial of BV in cutaneous T-cell lymphoma has confirmed its superiority to standard of care therapies. In this manuscript, we explore the history of CD30 as a tumor marker and as a therapeutic target, both in the laboratory and in the clinic, with a view to understanding future avenues for further study.

Excessive EDTA induces morphologic changes in bone marrow smears that mimic specific features of dysplasia.

INTRODUCTION: The WHO 2008 guidelines recommend that bone marrow (BM) slides for the morphological assessment of dysplasia should be made from freshly obtained BM specimens, and that specimens exposed to anticoagulants for more than two hours are unsatisfactory. However, BM aspirates may be exposed to excessive concentrations of anticoagulant, due to underfilling of the tube or inadequate mixing of the specimen. Here, we document the morphologic changes in BM smears resulting from exposure to excessive concentrations of ethylenediaminetetraacetic acid (EDTA). METHODS: Subjects with normal morphology in BM smears without anticoagulant were studied. Smears without anticoagulant and smears made from BM stored in excessive EDTA for 2 h at room temperature were stained with May-Grünwald Giemsa, and cell morphology was evaluated microscopically. Neutrophil and megakaryocyte size were measured using a calibrated microscope eyepiece graticule. RESULTS: Excessive EDTA concentrations induced progressive nuclear and cytoplasmic contraction with respective membrane damage, cell smudging and pyknotic nuclei. In the granulocytic and megakaryocytic series, hypolobated neutrophils, small neutrophils and micromegakaryocytes were increased in number. In erythroblasts, nuclear contour irregularities were induced, but in general, artifactual changes did not mimic dyserythropoiesis. With excessive EDTA concentrations, morphologic features of erythroblasts and megakaryocytes were obscured by nuclear and cytoplasmic contraction. CONCLUSION: Excessive EDTA induces morphologic changes in BM smears that mimic the specific dysplastic features of hypolobated neutrophils, small neutrophils, and micromegakaryocytes. BM aspirates should be collected into an appropriate concentration of EDTA to minimize such artifacts.