Christine Costello

Peripheral blood and bone marrow abnormalities in patients with HIV related disease

Between February 1983 and April 1986 we studied peripheral blood and bone marrow samples from 20 patients with human immunodeficiency virus (HIV) related disease. 14 patients had AIDS, three had ARC, two had PGL and one had ITP as a sole manifestation of HIV related disease.

Simultaneous or spontaneous occurrence of lympho- and myeloproliferative disorders: a report of four cases.

Summary. We describe four patients with mixed lympho‐ and myeloproliferative disorders. One patient had hairy cell leukaemia and acute myelomonocytic leukaemia, another lymphocytic lymphoma in leukaemic phase and chronic myelomonocytic leukaemia and the third patient had chronic lymphocytic leukaemia and polycythaemia rubra vera; none of these patients had received any prior therapy, and in two the diagnosis of the two malignancies was simultaneous. The fourth patient developed acute monocytic leukaemia 4 years after the diagnosis of chronic lymphocytic leukaemia after only 2 weeks of therapy with chlorambucil. The number of cases with concurrent or sequential but spontaneous occurrence of lympho‐ and myeloproliferative disorders reported so far is now 38. The questions relating to the pathogenesis of the two malignancies are discussed.

Chronic T-cell leukemias. I. Morphology, cytochemistry and ultrastructure

Abstract The morphology and cytochemistry of 15 cases of chronic T-cell leukemia: seven of T-CLL, six of T-PLL, 2 of T-LCL and 7 cases of Sezary syndrome, have been studied by light microscopy and transmission EM. T-CLL lymphocytes had moderately abundant basophilic cytoplasm with azurophilic granules. At EM the nuclear outline was irregular, there was abundant heterochromatin and the nucleolus was inconspicuous. Varying numbers of scattered electron dense granules and PTA were seen in the cytoplasm. In T-PLL the nucleolus was large and there was little chromatin condensation. Cytoplasmic granules were grouped in one area of the cytoplasm but not PTA were seen. T-LCl cells were pleomorphic with both blasts and mature forms with very irregular nuclei. There were granules but no PTA in the cytoplasm. Sezary cells had a cerebriform or deeply cleft nucleus; cytoplasmic granules were large and scanty. AP was positive both at light microscopy and at EM level in T-CLL and was confined to the granules. AP was less strongly positive in T-PLL and some of the granules were negative; it was negative in T-LCL while it was positive in the granules of Sezary cells. ANAE showed a strong dot-like positivity in T-PLL in contrast to a weak or negative reaction in T-CLL. Our findings show that the clinically heterogeneous chronic T-cell leukemias can be distinguished from each other on morphological and cytochemical grounds. These disorders reflect the proliferation of different subsets of mature (post thymic) T-lymphocytes. T-CLL being mainly a disease of Tγ cells and Sezary syndrome (and probably T-PLL) a disease of Tμ cells.

Prolymphocytic Leukaemia: an Ultrastructural Study of 22 Cases

. Twenty‐two cases of prolymphocytic leukaemia (PLL) have been studied by transmission electron microscopy (TEM); 17 had B‐cell surface markers (B‐PLL) and five had T‐cell characteristics (T‐PLL). The predominant cell, the prolymphocyte, has distinct features which were common to all cases: it is a relatively large lymphoid cell with a prominent nucleolus, well condensed peripheral nuclear chromatin and a variable amount of heterochromatin in intranuclear clumps.

Prolymphocytic Leukemia of B- and T-Cell Types

Prolymphocytic leukemia (PLL) is a distinct variant of chronic lymphocytic leukemia (CLL) [1, 2]. Although PLL may be suspected in patients with massive splenomegaly and lymphocyte counts over 100 × 109/1, the diagnosis can be made only by identifying the prolymphocyte as the predominant cell in well-prepared peripheral blood films. The typical morphological features of the prolymphocyte—namely, larger size than a normal blood lymphocyte (or CLL) slightly more cytoplasm, and a prominent nucleolus—are best appreciated at ultrastructural level [1, 3–7].

Ultrastructural Cytochemistry of Leukaemic Cells: Characterization of the Early Small Granules of Monoblasts

Summary An ultrastructural study of blast cells showing either monocytic or granulocytic differentiation was carried out with the acid phosphatase (AP) and myeloperoxidase (MPO) reactions. Eight cases of acute myeloid leukaemia (AML) and three of chronic granulocytic leukaemia in blast crisis were studied. A hitherto unrecognized small lysosomal granule characterized by AP activity and lack of MPO was present in the majority of cells of all six monoblastic leukaemias. These granules ranged from 0·05 to 0·2 μm in size and were distributed throughout the cytoplasm, frequently at the periphery of the cells. A small proportion of monoblasts showed AP reactivity in the Golgi cisternae. Both AP and MPO were positive in the granules of promonocytes; however, MPO positive granules were predominant in late promonocytes.

The Effect of Transfer Factor on Neutrophil Function in Chronic Mucocutaneous Candidiasis

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6‐year‐old boy is described. In addition to defects of in vivo and in vitro correlates of delayed‐type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub‐optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed‐type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

Cell Volume Studies in B-Cell Leukaemia

Summary Leucocyte volume histograms were obtained in 12 cases of B‐chronic lymphocytic leukaemia (B‐CLL), two cases of B‐prolymphocytic leukaemia (B‐PLL) and two cases of hairy‐cell leukaemia (HCL) by means of a Coulter model ZB1 linked to a channelyser. Visual examination of the histograms showed differences between the cases which were confirmed by measurement of the modal volume (MV) and the σ value (SD of log‐volume). The MV of the cells in B‐CLL ranged from 153·8 to 244·2 fl (mean 198·24 fl) and was lower than the MV in the cases of HCL (427·5 and 465·6 fl). One case of B‐PLL had cells with an MV within the B‐CLL range while in the other the MV was greater (317·9 fl). The histogram in one of two cases of B‐CLL in ‘prolymphocytoid’ transformation showed a relatively high σ value, thus suggesting heterogeneity in cell size. The volume histogram is a simple method of sizing the predominant cell in the peripheral blood in lymphoproliferative disorders and permits an objective comparison between cell sizes in different diseases.

Ultrastructure and Cell Marker Studies in Lymphoproliferative Disorders

Surface marker studies have been shown to provide new objective criteria which help to define normal and leukemic cells. Methods for recognizing different subpopulations of lymphocytes are in sharp contrast to conventional morphological techniques, e.g. Romanowsky stained films and paraffin sections, which not only do not allow such distinction to be made, but fail sometimes even to demonstrate the lymphoid or myeloid nature of a neoplastic process. Transmission electron microscopy (TEM) increases the precision of morphological analysis of cell types by demonstrating in greater detail, and with less artefacts, such cell characteristics as nuclear chromatin condensation, nuclear shape, details of cytoplasmic organelles, inclusions, etc. The combination of TEM and surface marker studies is bound, therefore, to increase our power of identification and characterisation of the cells involved in lymphoproliferative disorders.