Janet L. Parkin

Chronic lymphoproliterative disorder with unusual clinical, morphologic, ultrastructural and membrane surface marker characteristics

Four of 105 patients with chronic lymphocytic leukemia (CLL) manifested clinical, morphologic, ultrastructural and membrane surface marker characteristics that differed from those found in patients with typical CLL of demonstrated B-lymphocyte origin. These four patients presented with moderate increases in absolute lymphocyte counts, absolute neutropenia, polyclonal hypergammaglobulinemia and hepatosplenomegaly without lymphadenopathy. Two of them were unusually young, 19 and 25 years old, at the time of diagnosis. The proliferating lymphocytes carried receptors for sheep erythrocytes, a T-lymphocyte marker. In the three patients tested, the lymphocytes also carried Fc receptors. Ultrastructurally the lymphocytes contained cytoplasmic inclusion bodies consisting of parallel tubular arrays. The parallel tubular arrays corresponded to prominent cytoplasmic azurophilic granules on light microscopy. Parallel tubular arrays were found in less than 1 per cent of the lymphocytes in eight patients with typical B-lymphocyte CLL. The process in these four patients may be a distinctive chronic lymphoproliferative disorder originating in T lymphocytes with Fc receptors found in small numbers in the blood of normal persons.

Acute promyelocytic leukaemia: a study of 39 cases with identification of a hyperbasophilic microgranular variant

Thirty‐nine cases of acute promyelocytic leukaemia (APL) were divided into two morphological subgroups, typical hypergranular APL (31 cases) and microgranular APL (eight cases, 21%). The leukaemic cells in the microgranular APL cases were characterized by striking nuclear folding or lobulation; granulation was present in most of these cells but was less abundant and finer than in typical APL. In three microgranular APL cases a distinctive small leukaemic promyelocyte with unusual nuclear lobulation and deeply basophilic cytoplasm containing few or no visable granules was the predominant leukaemic cell. This small hyperbasophilic promyelocyte was also present as a minor population of cells in the other five microgranular APL cases and in 28 of the 31 typical APL cases. Ultrastructurally the most abundant promyelocytes in microgranular APL had smaller and usually fewer granules than in typical APL; other characteristic ultrastructural features of APL were found with equal frequency. The median blood leucocyte count was significantly higher in microgranular APL, 83·0 × 109/1, than in typical APL, 1 · 8 × 109/1 (P < 0 · 01). The median duration of complete remission (CR) for microgranular APL, 6 · 5 months, was shorter than the 21 + month median CR for typical APL. The morphological characteristics of microgranular APL may mimic those of myelomonocytic leukaemia; however, the presence of cells with multiple Auer rods, large inclusions of Auer‐like material and the small hyperbasophilic promyelocytes are important distinguishing features. In equivocal cases cytochemistry, electron microscopy and cytogenetic studies may verify the diagnosis.

Philadelphia chromosome-positive blastic leukaemia: ultrastructural and ultracytochemical evidence of basophil and mast cell differentiation.

Summary. Ultrastructural, ultracytochemical, immunologic and biochemical studies were performed on leukaemic cells from 41 patients with Philadelphia chromosome‐positive blastic leukaemia; 28 patients were in blast transformation of chronic myelogenous leukaemia and 13 patients presented with ‘acute’leukaemia. The patients were divided into two morphologic groups, lymphoid (16 cases) and myeloid (25 cases), on the basis of light microscopy and cytochemistry. All lymphoid cases studied for the presence of CALLA (10 patients) and TdT (11 patients) were positive. Two of 13 myeloid cases studied were TdT positive. The blasts from 10 of 16 lymphoid cases contained immature basophil/mast cell granules on ultrastructural examination. Peroxidase‐positive ‘lymphoid’blasts were noted in three of seven patients studied by ultracytochemical techniques. The reactivity was primarily confined to granular structures. Of the 25 cases in the myeloid group, blasts from 14 cases showed basophil/mast cell differentiation, nine cases showed neutrophil/monocyte features, and two cases were megakaryoblastic. Distinct patterns of ultrastructural peroxidase positivity were seen in the seven myeloid cases studied. In basophil/mast cell precursors the reactivity was primarily confined to granules; neutrophil precursors showed reactivity in the nuclear envelope, rough endoplasmic reticulum (RER), golgi and granules; in megakaryoblasts, only the nuclear envelope and RER were positive while the granules were consistently negative.

Morphologic and ultrastructural characteristics of T‐cell acute lymphoblastic leukemia

The morphology, ultrastructure, and acid phosphatase activity of the leukemic cells of 11 cases of T‐cell acute lymphoblastic leukemia (T‐ALL) were studied. Distinctive small cells with markedly hyperchromatic convoluted nuclei comprised from 2 to 25% of the leukemic cells in the blood and bone marrow smears of 10 of the 11 patients. Similar cells were found in only four of 47 cases on non‐T, non‐B‐ALL. Many of these small leukemic cells exhibited ultrastructurally nuclear membrane reduplication and nuclear blebs and splits. The presence of these small leukemic cells with markedly hyperchromatic convoluted nuclei in ALL is strongly suggestive of T‐ALL. This cytomorphologic finding, when combined with the presence of strong focal acid phosphatase activity, lends even greater predictability of a T‐cell process.

Ultrastructural characteristics of therapy-related acute nonlymphocytic leukemia: evidence for a panmyelosis

Leukemic cells from 13 patients with therapy‐related acute nonlymphocytic leukemia (ANLL) were studied by electron microscopy. All of the patients had radiotherapy, and/or alkylating agent chemotherapy for other neoplastic disease 25 to 182 months prior to the diagnosis of ANLL. All cases manifested ultrastructural evidence of a panmyelopathy. All marrow cell lines exhibited nuclear‐cytoplasmic asynchrony and abnormalities of cell size. Developing granulocytes exhibited decreased primary and/or secondary granule formation and abnormal granules characterized by irregular shape, large size and internal membranous lamellae. Monocytes showed perinuclear bundles of microfilaments. In some cases, the predominant leukemic blasts showed evidence of early basophil granule development which was not appreciated in light microscopy. Abnormalities in erythroid cells included abundant intracristal mitochondrial iron, large vacuoles, infoldings of redundant membrane and membrane‐bound nuclear blebs and intranuclear clefts. Megakaryocytes manifested decreased numbers of granules and demarcation membranes. Excessively large platelets with decreased or abnormal granules were identified; giant compound granules with irregular contour and variable electron density were present. Several of the changes in the developing hematopoietic cells were similar to those described in preleukemia and in certain nonneoplastic disorders. The consistent panmyelosis in therapy‐related ANLL together with several uniform clinical features defines a specific clinicopathologic entity.

Tubular complexes of endoplasmic reticulum in myeloblasts of acute myelogenous leukemia.

The leukemic cells from 9 patients with acute myelogenous leukemia were studied by light microscopy, cytochemistry, and electron microscopy. In Wright-Giemsa-stained blood and bone marrow preparations, from less than 1% to greater than 95% of the leukemic cells from the 9 patients contained inclusions that measured one-third to one-half the diameter of the cell. In 4 patients the inclusions appeared to be associated with intense focal myeloperoxidase activity. Ultrastructural studies demonstrated that the inclusions were complexes of smooth, membranous, anastomosing 50-nm tubules and 80-nm particles. These complexes were surrounded by bundles of microfilaments and numerous mitochondria. The tubular complexes resembled the tubuloreticular structures that have been reported in lymphoreticular and endothelial cells from patients with autoimmune and viral diseases.

Primary Skin Malignancy with Features Suggestive of Dendritic Reticulum Cell Differentiation

A 72-year-old man developed recurring skin lesions. Multiple biopsies revealed a skin malignancy with histologic features of lymphoma. The bone marrow was subsequently replaced by tumor. Immunologic and ultrastructural features of the tumor cells suggested dendritic reticulum cell differentiation.

Ultrastructural Observations in Therapy-Related Panmyelosis

Acute nonlymphocytic leukemia occurring in individuals having received alkylating agent chemotherapy and/or radiotherapy is a well-recognized complication of treatment of hematologic and nonhematologic malignancies and certain nonneoplastic disorders [1–9]. The incidence of acute leukemia in these patients is not well established but appears to be related to the intensity of therapy and age of the patient [10–12]. The interval from the commencement of the treatment of the primary disease to the recognition of the secondary leukemia varies considerably; in the patients studied in this institution it has ranged from 25 to 182 months, with a median interval of 66 months. Response to treatment for the therapy-related leukemias has generally been poor and survival has been shorter than for non-therapy-related acute myelogenous leukemia [13–15].