G. F. Burns

A chronic lymphoproliferative disorder with distinctive features: a distinct variant of hairy-cell leukaemia

Abstract Two patients with a unique combination of clinical, haematological, pathological and immunological features are described. These features included a chronic course without significant constitutional symptoms, substantial splenomegaly without other organomegaly, a high WBC count with many abnormal mononuclear cells but without neutropenia or monocytopenia, and an easily aspirable marrow with well-preserved haematopoiesis and a modest infiltrate of mononuclear cells. The splenic architecture was completely replaced by a diffuse infiltrate of mononuclear cells, with prominent involvement of the red pulp. The bone marrow was also diffusely involved, but increased reticulin fibres were not a feature. Neither the MCV nor the LAP score was elevated. The abnormal mononuclear cells possessed striking surface hairs and strong tartrate-resistant acid phosphatase, but differed markedly from the pathognomonic cells of hairy-cell leukaemia in their internal structure. The cells were phagocytic and their surface-marker phenotype was E−γFc+μFc+C3−Mo−SIgG+. These cases are compared and contrasted with similar clinical entities including hairy-cell leukaemia, chronic lymphocytic leukaemia, prolymphocytic leukaemia and certain non-Hodgkins lymphomata and it is concluded that the features of their disease are sufficiently distinctive to justify their recognition as a distinct variant of hairy-cell leukaemia. It is proposed to term the entity Type II hairy-cell leukaemia as compared with the usual form of hairy-cell leukaemia, Type I.

New evidence relating to the nature and origin of the hairy cell of leukaemic reticuloendotheliosis.

Summary. New evidence is presented concerning the nature and origin of the pathognomonic cell of leukaemic reticuloendotheliosis (LRE). A specific receptor for IgM was demonstrated by an EAIgM rosette test in all seven cases of LRE studied. This marker was absent from the pathological cells of a wide variety of haematological proliferative disorders, and from cells of the normal myeloid and monocyte‐histiocyte series. A small percentage of circulating mononuclear cells which did not resemble monocytes morphologically, did possess the receptor for IgM. The LRE cells were found to show variable phagocytic activity for IgG opsonized erythro‐cytes and latex particles. Studies of differences in the kinetics of the rosette test in the seven cases together with the range of phagocytic activity and cytological maturity observed, suggested that the diagnosis of LRE may encompass a broader spectrum of clinical and cytological features than has previously been recognized. Evidence presented suggests that the cells of LRE are not related to either B‐lymphocytes or the monocyte‐histiocyte series. It is proposed that LRE represents a leukaemic proliferation of the newly identified small population of EAIgM receptor bearing normal circulating mononuclear cells.

Identification of the hairy cells of leukaemic reticuloendotheliosis by an esterase method.

A distinctive pattern of alpha‐naphthyl butyrate esterase positivity was observed in all of a series of 14 patients with HCL. This pattern was not observed in a range of other haematological malignancies including nine cases of CLL, two cases of Sézarys syndrome, six cases of null cell ALL, two cases of Schilling‐type monocytic leukaemia and one case of lymphosarcoma cell leukaemia. The potential diagnostic value of this simple cytochemical test is discussed in relation to existing methods.

Cytochemical, ultrastructural and immunological studies of circulating Reed-Sternberg cells.

Reed–Sternberg (R–S) cells in the circulating blood of a patient with Hodgkins disease were cytochemically peroxidase and Sudan black negative, devoid of alkaline phosphatase and non‐specific esterase, mostly PAS negative but occasionally showing positivity, and nearly always showing moderately strong granular positivity for acid phosphatase. Electron microscopy showed irregular nuclear profiles, conspicuous nucleoli, a moderate development of cytoplasmic organelles but absence of structures resembling monocytic granules. The R–S cells frequently possessed receptors for the Fc region of IgG and were mostly positive for SmIg, but did not form rosettes with sheep or mouse erythrocytes nor have receptors for the Fc region of IgM or the C3 component of complement. The combined results suggest that R–S cells are of B‐cell lineage.

Hairy-cell leukaemia: A B-cell neoplasm with a severe deficiency of circulating normal B lymphocytes

Abstract A series of 10 patients with hairy-cell leukaemia (HCL) was studied. The hairy cells (HCs) of all the patients studied possessed surface membrane immunoglobulin of a single light chain type (Smlg) not acquired from the serum. Combined Smlg, esterase cytochemical, ultrastructural, surface marker and serological studies showed that many more cells were involved in the B-cell neoplastic proliferation than was apparent by simple morphological examination. In addition, the virtual absence of cells rosetting with yeast-C3b indicator particles, and of cells displaying a B-cell esterase pattern or possessing the non-predominant light chain Smlg, indicated a severe deficiency of circulating normal B lymphocytes in HCL.

Membrane Receptors of Human Leukaemic Myeloid Cells: Sequential Expression of the γFc Receptor

Summary. An immunological surface marker study was performed on 13 patients with a variety of myeloid leukaemias. It was shown that expression of the receptor for the Fc of IgG (γFcR) starts to take place at the promyelocyte stage, and that the receptor is present on more mature granulocytic cells, but is absent from myeloblasts. Myeloblasts and promyelocytes are negative for the complement receptor CR2. Monoblasts, unlike myelobasts, were shown to express a γFcR and, to a lesser extent, CR2. Receptor expression therefore appears to be an earlier event in monocytic development. The possible diagnostic value of immunological marker studies in myeloid disorders is considered.

LEUCOCYTE ALKALINE PHOSPHATASE SCORES IN HAIRY CELL LEUKAEMIA

We have also had the opportunity to study four untreated patients with acute lymphoblastic leukaemia (ALL) where histological and immunological classifications were available. As shown in Table 11, lymphoblasts from patient I were histologically prolymphocytic and expressed C3 receptors without other B-cell markers; however, the ADA activity (0.03 5 ) suggests a B-lymphocyte origin based on data shown in Table I. The remaining patients’ bone marrow lymphoblasts were histologically classlfied as prolymphocytic in two cases, prolymphoblastic in one case, and all three were classdied as null cells by immunological markers. In each of these patients, ADA activity in bone marrow lymphoblasts was in the range of that observed in lymphoid populations with T-cell characteristics. These results are consistent with recent reports showing that null lymphoblasts in ALL can be classified as being of T or B-cell lineage as determined by specific antisera (Fu et al, 1975; Kaplan et al, 1977). The results indicate that ADA activity in leukaemic lymphoblasts correlates with the cells from which they are derived. This statement is further corroborated by the studies ofTung et al (1976), who demonstrated that B lymphocytes have low ADA activity compared to T lymphocytes. The determination of ADA activity may provide another useful marker for classifying ALL and other lymphoid leukaemias as either of Bor T-lymphocyte origin.