Megakaryoblastic transformation of chronic granulocytic leukaemia. An electron microscopy and cytochemial study.

Abstract

SUMMARY Morphological, cytochemical, and ultrastructural electron microscopic (EM) studies were performed on blood and bone-marrow cells of a case of Ph'-positive chronic granulocytic leukaemia in megakaryocytic acute transformation. The entire leukaemic cell population was found to consist of megakaryoblasts and megakaryocytes. Intermediate stages of maturation between blasts and micromegakaryocytes were observed at EM level.Micromegakaryocytes, usually mononuclear or binuclear, have been recognised as a significant component of the bone marrow in acute myeloid leukaemia (AML), in the preleukaemic stage of AML, and in refractory anaemia with an excess of myeloblasts. In the patient reported here virtual replacement of the marrow by micromegakaryocytes was the chief manifestation of the transformed stage of Philadelphia positive chronic granulocytic leukaemia (CGL). This case accents the fact that CGL is a stem-cell defect, rather than a defect only of granulocytic precursors, and is a further illustration of the failure of megakaryocyte polyploidisation in myeloid malignancy. Case reportThe patient (IS) was a 44-year-old schoolteacher who had been in good health until January 1975, when she presented for medical attention because of increasing abdominal girth. She gave a history of two months' lethargy, dyspnoea, and mild ankle swelling. She had suffered occasional night sweats. Her only relevant past history was of phlebitis in the right leg one year previously. On examination she was pale and the speen was enlarged 18 cm below the left costal margin; the liver was just palpable. Haematological findingsThe haemoglobin (Hb) was 6-6 g/dl and the leucocyte count was 290 x 109/l with 1 % blasts, 7% promyelocytes, 17 % myelocytes, 25 % metamyelocytes, 39 % neutrophils, 3 % basophils, and 3 % eosinophils. There was one nucleated red cell per 100 white blood cells. The neutrophil alkaline phosphatase score (NAP) was 2. Direct examination of the peripheral blood revealed the presence of the Philadelphia chromosome (Ph'). A bone marrow aspirate showed the marrow to be markedly hypercellular with hyperplasia of neutrophil, eosinophil, and basophil lines. Megakaryocytes were increased and an increased percentage of mononuclear and non-segmented forms was noted. A diagnosis of chronic granulocytic leukaemia was made.The initial treatment was by leucapheresis and peripheral blood leucocytes were frozen and stored in liquid nitrogen (Lowenthal et al., 1976). Subsequently, control was achieved with demecolcine for two months followed by busulphan. Seven months after presentation she was submitted to elective splenectomy as part of a programme to assess the place of splenectomy in chronic granulocytic leukaemia. Before splenectomy the patient was clinically well, and the liver and spleen were impalpable. The Hb was 13X3 g/dl, the leucocyte count was 6-4 x 109/l, and the platelet count was 344 x 109/l. Immature granulocytic cells and circulating erythroblasts were not seen in the peripheral blood.After splenectomy the patient...

Chronic myeloid leukemia: Manifesting as spontaneous splenic rupture and terminating in megakaryoblastic transformation

“…The results of positive PAS and AP reactions, combined with the positive ANAE activity, which was partially inhibited by sodium fluoride and a negative reaction to ANBE were almost identical with the one observed in normal MK [23]. These findings were also consistent with the cytochemical features of megakaryoblastic leukemia described by the FAB group [22] and similar to those observed by Bain et al [24] in a case of MKB crisis of CML. Recently, MK origin of the cells can be identified definitely by the demonstration of 1) PPO, a specific enzyme marker of normal or neoplastic MK and their precursors, at the electron microscopic level [ 13-15,251, 2) platelet-and MK-specific membrane glycoproteins by reaction with monoclonal antibodies [11,26,17], and 3) factor VLlI antigen [12, 281.…”

The Blast Crisis of Chronic Granulocytic Leukaemia: Megakaryoblastic Nature of Cells as Revealed by the Presence of Platelet‐Peroxidase—A Cytochemical Ultrastructural Study

“…More recently the possible megakaryoblastic nature of cells in CGL blast crisis has been proposed (Castoldi et al, 1975;Hossfeld ef al, 197s;Bain et al, 1977). Our study, based on ultrastructural cytochemistry, gives confirmation of this proposition.…”

“…Although blasts had a lymphoblastic appearance in a minority of cases, other features, the presence of micromegakaryocytes (mMK) and prominent abnormalities in the megakaryocytic series suggested a myeloproliferative syndrome (Peterson et al, 1976). One patient terminated as megakaryocytic leukaemia (Ogawa et al, 1970) and in others, some blasts were suspected megakaryoblasts (MKB) (Castoldi et al, 1975;Huhn & Ascher, 1975;Peterson et al, 1976;Bain et al, 1977). Difficulties in identifying MKB arise from the lack of evidence of cytoplasmic maturation in small cells.…”

Erythroblastic transformation of chronic granulocytic leukemia: A clinical and cytogenetic case study

“…Additional cytogenetic abnormalities occur in 8040% of patients with Philadelphia chromosome-positive (Ph') chronic granulocytic leukemia (CGL) with the development of blastic transformation [ 11. These abnormalities are frequently nonrandom, viz, trisoniy 8, extra Ph', and an isochromosome of the long arms of chromosome 17 [2]. Blastic transformation is usually of the myeloblastic variety but lymphoblastic [3], megakaryoblastic [4], and erythroblastic types [5] have been described. To date, little correlation has been found between the different morphologic varieties and the additional chromosomal abnormalities.…”