Bone Marrow Picture Research Articles

The 2001 World Health Organization and Updated European Clinical and Pathological Criteria for the Diagnosis, Classification, and Staging of the Philadelphia Chromosome-Negative Chronic Myeloproliferative Disorders

The clinical criteria according to the Polycythemia Vera Study Group (PVSG) do not distinguish between essential thrombocythemia (ET), thrombocythemia associated with early-stage polycythemia vera (PV) and prefibrotic chronic idiopathic myelofibrosis (CIMF). The criteria only classify the advanced stage of PV with increased red cell mass. The classification of myeloproliferative disorders (MPDs), proposed by the World Health Organization (WHO) in 2001, is a compromise of the clinical PVSG and WHO bone marrow criteria, and excludes early stages of ET and PV. The updated European clinical and pathological criteria combine the WHO bone marrow criteria with established and new clinical, laboratory, biological, and molecular MPD markers. This allows clinicians and pathologists to diagnose early-stage MPD and to differentiate ET, PV, and prefibrotic chronic idiopathic myelofibrosis (CIMF). Depending on laboratory tests and diagnostic criteria used, the population of the MPD patients defined as ET, PV, and CIMF are heterogeneous at the clinical, laboratory, and biological and pathological levels. The recent discovery of the JAK2 V617F mutation, which is the cause of a distinct trilinear MPD in its manifold clinical manifestations during long-term follow-up, increases the specificity of a positive JAK2 V617F polymerase chain reaction (PCR) test for the diagnosis of MPD (near 100%), but only half of the ET and CIMF patients according to the PVSG (sensitivity 50%) and the majority of PV patients (sensitivity 95%) are JAK2 V617F positive. A comparison of the laboratory features of JAK2 V617-positive and JAK2 wild-type ET patients clearly showed that JAK2 V617-positive ET is characterized by higher values for hemoglobin, hematocrit, and neutrophil counts; lower values for serum erythropoietin (EPO) levels, serum ferritin, and mean corpuscular volume; and by increased cellularity of the bone marrow in biopsy material. This indicates that JAK2 V617-positive ET patients, diagnosed according to the PVSG criteria, represent a "forme fruste of PV" consistent with early PV mimicking ET (JAK2 V617F trilinear MPD). In contrast, the JAK2 wild-type ET patients had significantly higher platelet counts and usually had a clinical picture of ET with normal serum EPO levels, PRV-1 expression, and leukocyte alkaline phosphatase score, and a typical WHO ET bone marrow picture. The clinical and pathological data on JAK2 V617F-positive MPD patients suggest that the JAK2 V617F mutation defines one disease entity with several sequential steps of ET, PV, and secondary myelofibrosis during long-term follow-up, and that the wild-type JAK2 MPDs may represent another distinct entity with a related but different molecular etiology. MPD-specific markers such as serum EPO, endogenous erythroid colony formation (EEC), and JAK2 V617F have high specificities, but the sensitivities are not high enough to detect the early stages of the MPDs, ET, PV, and prefibrotic CIMF. Bone marrow histopathology in addition to clinical, laboratory, biological, and molecular markers, including the JAK2 V617 PCR test, serum EPO, PRV-1, EEC, LAP score, peripheral blood parameters, and spleen size on echogram will detect the early stages of MPD and allows diagnostic differentiation of the three primary MPDs (ET, PV, and CIMF) in both JAK2 V617F-positive and JAK2 wild-type MPD patients.

Necrobiotic xanthogranuloma associated with paraproteinemia and non‐Hodgkin's lymphoma developing into chronic lymphocytic leukemia: the first case reported in the literature and review of the literature

A 56-year-old married female presented in May 1998 with a 5-month history of xanthelasma of the eyelids, followed 4 months later by two enlarged lymph nodes of the left side of the neck and three of the left axilla. At the same time, she developed xanthomatous patches on the face, neck, and shoulders (Fig. 1). The cutaneous lesions were xanthomatous nodules and plaques, affecting the periorbital regions. Later, the whole face was affected, followed by ulcerated lesions on the scalp, chest, back, and extremities (Fig. 2). The skin lesions became painful, pruritic, ulcerated tumors (Fig. 3). In July 1998, computed tomography (CT) scans of the chest and abdomen with contrast medium showed pretracheal, bilateral axillary, right retrochural, paracaval, aortocaval, and para-aortic lymph node enlargement. These findings were suggestive of lymphoma. CT scan also showed slight heterogeneous hypodensity in the upper part of the right lobe of the liver, suggesting fatty infiltration. The spleen, pancreas, and suprarenal glands appeared normal. One cervical and two left axillary lymph nodes were excised. They revealed total replacement of the nodular architecture by a diffuse proliferation of mature lymphoid cells having small nuclei and a crumbled chromatin pattern, and very rare mitosis. It was concluded from the lymph node biopsies that these changes were typical of non-Hodgkin's lymphoma, diffuse and small cell type, of low-grade malignancy. A bone marrow aspirate showed a marrow heavily infiltrated by lymphoid cells with some immaturity. The megakaryopoiesis was adequate. Trephine biopsies showed similar changes. Iron stores appeared to be absent. The bone marrow picture was consistent with diffuse, well-differentiated non-Hodgkin's lymphoma, developing into chronic lymphocytic leukemia (CLL). Endoscopy showed antral-type gastric mucosa exhibiting mild chronic gastritis. Skin biopsy from a fresh lesion on the back showed a diffuse inflammatory cell infiltrate with collections of histiocytic cells. It also showed necrobiotic foci, surrounded by mixed inflammatory cells, dark palisaded foamy histiocytes, and a few Touton giant cells. These findings are compatible with necrobiotic xanthogranuloma (NXG) (Figs 4 and 5). Blood film showed normochromic, normocytic erythrocytes with anisopoikilocytotic leukocytes and normal platelets. The sedimentation rate was 90 mm in the first hour. The blood picture also showed monoclonal IgG paraprotein (3170 mg/dL) of the kappa light chain type. The patient was treated by the oncologist for her lymphoma, and was given Cytoxan, prednisolone, endoxan, Leukeran, and melphalan. She showed an excellent response to pulsed treatment with steroids (60 mg prednisolone orally daily for 5 days, repeated every month for 6 months). She also responded to Leukeran at a dose of 5 mg daily for 5 days every month for 6 months, and showed regression in the size of the lymph nodes. The treatment of her skin lesions was unsatisfactory in spite of the fact that she was given cyclosporine and both systemic and topical corticosteroids.

Sino-orbital chloroma presenting as unilateral proptosis in a boy

Granulocytic sarcoma or chloroma is an unusual localized tumor composed of cells of myeloid origin. Involvement of the orbit and the ethmoid sinuses and presenting as proptosis is rare. Diagnosis could be difficult and delayed when there are no other systemic manifestations, especially with normal peripheral blood and bone marrow picture. We present one such case with unilateral proptosis as the sole presenting sign that posed a diagnostic challenge to us. Orbital decompression by an otolaryngologist may have a role in managing such a case.

Clinical observation on treatment of acute myelocytic leukemia by supplementing Qi, Nourishing Yin and clearing heat principle

To observe the clinical efficacy of TCM with supplementing Qi, nourishing Yin and clearing heat principle (SQNYCH) combined with chemotherapy in treating myelocytic leukemia. One hundred and fourteen patients were randomly divided into the treated group (n = 68) and the control group (n = 46). To the treated group, SQNYCH was applied as the basic treatment, with combined chemotherapeutic protocol, using DA, HA and IA, to induce remission, and to the M3 patients, all-trans retinoic acid and arsenic trioxide were given. As for patients in the control group, only western medicine was administered. In the treated group 49 patients (72.1%) were completely remitted, 9 (13.2%) partially remitted and the total remission rate being 85.3%, which was significantly different from that in the control group. After treatment, the blood and bone marrow picture were obviously improved in both groups, but the increase of hemoglobin and platelet were better in the treated group than in the control group (P < 0.05 or P < 0.01). Immune functions were enhanced in both groups, but the elevation of CD4, CD4/CD8 ratio and NK cells were higher in the treated group than in the control group (P < 0.05 and P < 0.01). Application of SQNYCH principle in treating acute myelocytic leukemia could elevate the clinical efficacy, which is of great value in clinical practice.

Chronic myeloid leukemia presenting with absence of basophils and marked dyspoiesis

A 61-year old woman presented to us with fever, weakness and ecchymotic patches for one year. She had leucocytosis, anemia and thrombocytopenia. Peripheral blood smear showed 62% neutrophils, 32% myelocytes and metamyelocytes, 2% promyelocytes, 1% blasts, 2% monocytes, 1% lymphocytes but no basophils and marked dyspoiesis. Bone marrow picture was essentially the same. A diagnosis of atypical chronic myeloid leukemia was suggested. The correct diagnosis of chronic myeloid leukemia-accelerated phase was, however, made on cytogenetic analysis which showed Philadelphia chromosome (Ph) and isochromosome 17q [i(17q)]. This case describes a rare and diagnostically difficult presentation of CML arising out of a combination of prominent dyspoiesis and near absence of peripheral blood basophils.

Sideroblastic anaemias.

Sideroblastic anaemias.

Concurrent Langerhans cell histiocytosis and myelodysplasia in children

Background Langerhans cell histiocytosis (LCH) is characterized by the proliferation of abnormal histiocytes (Langerhans cells), whose origin as a reactive process or a neoplastic disorder is still poorly understood. Although LCH has been recorded as being associated with malignant neoplasms, concurrence of LCH and myelodysplastic syndrome has not been reported so far. Procedure We report on four children aged 23, 25, 26, and 53 months with multisystem LCH with organ dysfunction (bone marrow and liver) whose bone marrow pictures, taken at diagnosis, revealed the presence of myelodysplastic abnormalities (RA, RAEB, RAEB-t). Results We suggest that the commonly used expression of “organ dysfunction,” which refers to clinical and functional alterations, could be explained by a myelodysplastic-like disorder. Conclusions The contemporary presence of both events may provide a better understanding of the pathogenesis of LCH, especially in young children with multisystem disease and organ dysfunction, who are known to have a very poor outcome. Med. Pediatr. Oncol. 35:421–425, 2000. © 2000 Wiley-Liss, Inc.

Phagocytose élective de polynucléaires neutrophiles par les macrophages médullaires et neutropénie auto-immune de l'enfant

Autoimmune neutropenia (AIN) is a frequent cause of chronic neutropenia especially in youngest children. Its diagnosis is established by immunological proof of the autoimmune mechanism. The aim of this study is to better describe this autoimmune process and to show the contribution of bone marrow smears to this diagnosis. Patients and methods. — Ten children, six girls and four boys, were examined between 1990 and 1995. Eight of them had typical AIN, confirmed by the presence of antibodies against neutrophils. Two other patients were included on the basis of bone marrow pictures. Five non-neutropenic children with normal bone marrow smears were chosen as controls. Bone marrow analysis was always performed by the same cytologist according to a reproducible technique. Results. — Six out of ten patients had important features of elective phagocytosis of neutrophils by marrow macrophages (unlike controls) without signs of dysgranulopoiesis or hemophagocytosis. Antibodies against neutrophils were detected in six patients with phagocytosis and in four patients without these cytological features. In two other children presenting the same bone marrow picture and clinical profile, an autoimmune process was probable, even in the absence of antibodies against neutrophils. Some patients had several infections and were given immunoglobulins and/or granulocyte colony-stimulating factor (G-CSF) therapy. The efficacy of Immunoglobulin was not constant, whereas G-CSF was effective at low doses and shortened the duration of infections. Conclusion. — Prolonged neutropenia in childhood must lead to look for phagocytosis by marrow macrophages in bone marrow smears, as a possible sign of autoimmunity. Growth factors may temporarily be used associated with antibiotics therapy in severe and prolonged infections.

A CASE OF HEMOLYTIC UREMIC SYNDROME (HUS) ASSOCIATED WITH THROMBOCYTOSIS AFTER SPLENECTOMY

A 23-year-old woman underwent a total splenectomy for rupture of the spleen due to a trafficaccident. On admission, a mild thrombocytosis was noted and the resected spleen was 147g in weight, showing a slight splenoma. After the operation, thrombocytosis became prominent and aspirin and dipyridamole were administerted to prevent thrombosis, but the platelet count increased to 1, 950, 000/mm8 on the 14th hospital day. On the 31st postoperative day, hemoglobinuria appeared abruptly, and relative thrombocytopenia, high level of LDH, increase in BUN, and appearance of clastic erythrocytes were confirmed. The patient was diagnosed as hemolytic uremic syndrome (HUS). HUS was successfully managed by administration of ticlopidine and heparin while it stayed in a relatively mild state. As of 3 months after the operation, however, the platelet count is still kept at high level, around 1, 200, 000/mm8 and antiplatelet regimen is still continued. No case of HUS caused by thrombocytosis has been reported as far as we could review, and this case is so rare. In this case, an increase in megakaryocytes was noted in a bone marrow picture. In is thought that underlying primary thrombocytosis might cause this abnormal increase in platelets.

Rhabdomyosarcoma Presenting as Acute Leukemia

We describe a case of a very unusual presentation of rhabdomyosarcoma. An 18-year-old woman presented with symptoms and signs compatible with acute leukemia. The bone marrow picture showed diffuse involvement sustained by undifferentiated blasts that turned out to be of striated muscle origin by immunochemistry. While it is well known that rhabdomyosarcoma may metastasize to the bone marrow, extensive marrow involvement with leukemic spread as a unique clinical manifestation is extremely rare. Our observation further confirms the need to consider rhabdomyosarcoma among the possible differential diagnoses in patients who present with a leukemic picture and atypical blasts lacking all hematopoietic markers.

Acquired pure red cell aplasia: a study of six cases

Persistent infection by parvovirus B19 associated with pure red cell aplasia (PRCA) has been documented in immunocompromised patients. Bone marrow failure is associated with conditions in which immune surveillance is impaired, and in these instances occult parvovirus infection may be suspected. In this study we have assessed by serological and molecular methods whether parvovirus B19 infection may be a more frequent cause of PRCA than hitherto suspected and whether it may be present in the absence of a typical bone marrow picture. Six patients with PRCA--two with isolated PRCA and no apparent underlying disease, two with a lymphoproliferative disease, one with thymoma, and one with chronic myelomonocytic leukemia--have been studied. Four of the six patients had overt PCRA and were clearly immunocompromised. Parvovirus B19 was not detected in any of the six patients by PCR analysis and serology investigating the presence of IgM or IgG antibodies. Although parvovirus B19 infection needs to be ruled out in PRCA it represents only one, and probably not the most frequent, etiological factor of PRCA.

A CASE OF HAIRY CELL LEUKEMIA PRESENTING WITH A SPLENOMA WHICH OFFERED DIFFICULTY IN DIAGNOSIS

A 52-year-old woman was seen at the hospital for close examination, because she was pointed out having a splenoma at a nearby hospital when she visited there complaining of abdominal distention. There were no fever, anemia, and jaundice. No superficial lymph nodes were palpated. In the abdomen the spleen extending from an area under the left costal arch to the infraumbilical area was palpated. Abdominal CT and echography revealed a giant splenoma with homogenous internal structure. The liver had no morphological abnormalities nor tumor shadow. No lymph node swelling was also shown. There were no hepatitis nor abnormal findings in peripheral blood (white blood cell fraction), blood biochemical tests, tumor markers, neutrophilic Al-p value, and bone marrow picture. No causative disease for the splenoma was able to be determined preoperatively, and a possibility of lymphoma arising in the spleen or leukemia was not ruled out. So, splenectomy was performed in order to diagnose and to alleviated the symptoms. The excised spleen was 1, 860 g in weight and 24.3×14.7×5.8cm in size. Pathologically it was diagnosed as hairy cell leukemia. This disease is uncommonly encountered, but we should entertain it as a probable differential diagnosis for giant splenoma. This paper presents this case with a review of the literature.

IgE pyroglobulinemia in multiple myeloma

A new case of IgE/K myeloma in a 38-year-old male is described. The clinical course, bone marrow picture and serum electrophoretic pattern were typical of multiple myeloma. Heating of the serum at 56°C induced an irreversible gel formation or pyroglobulin that was isolated and proved to be identical to the IgE paraprotein, by biochemical and immunochemical methods. The thermoprecipitability was abolished by treatment with urea, sodium dodecyl sulphate and neutral salts and not inhibited by sugars, alcohols, 2-β-mercaptoethanol and guanidine HC1. The association of an IgE myeloma protein with a pyroglobulin is a finding not previously reported in a myeloma of this class.

The influence of a growth promoter (Zeranol) on the growth rate, haemogram, myelogram and selected blood biochemical value of calves

Summary Implantation of Zeranol in calves caused an improvement in mean liveweight gain which was greater in bull calves than in heifer calves. Among heifer calves, implantation had no significant effect on haematological values, but serum urea was significantly lowered. Implanted bull calves had lower mean haemoglobin (Hb) concentration, red blood cell count and mean cell Hb concentration values, but they had higher mean cell volume (MCV) and mean cell Hb values than control calves. Mean serum albumin and albumin-to-globulin (A/G) ratio were significantly higher in implanted than in control bull calves. These haematological changes were reflected in the bone marrow picture of bull calves by a significantly lower myeloid erythroid (M/E) ratio in implanted than in control calves. Different responses to the drug in male and female calves may have been caused by age and weight differences between them when the experiment was carried out.

Changes in the blood and the bone marrow picture of the pharaoh quail ( Coturnix coturnix pharaoh) chicks as a manifestation of adaptation to postembryonal life

1. 1. The aim was determination of the rate of adaptation of the respiratory and defence functions of the blood and bone marrow of quail chicks. 2. 2. In the early post-hatching period, enhanced haemoglobin synthesis is the mechanism adapting the bird to the rich oxygen conditions beyond the egg. 3. 3. In 2-week-old chicks, the increased respiratory function of the blood is associated with a parallel rise of the erythrocyte count and haemoglobin content. 4. 4. The defence mechanisms of the chick in the first days after hatching are mainly connected with a high content of heterophilic granulocytes and in older chicks with a rising lymphocyte count.

Clinical significance of cytostasis activity of mononuclear cells in childhood acute lymphoblastic leukemia.

Cytostasis activity of mononuclear cells (MNC) was studied in 32 children with acute lymphoblastic leukemia (ALL) with special reference to the relapse of the disease. MNC from ALL even in complete remission had decreased cytostasis activity. The cytostasis activity in ALL patients who relapsed within 3 months after the assay was significantly lower than that of the patients who continued to be in remission for more than 6 months after the assay. Serial assays in six patients demonstrated that a sudden decrease of the cytostasis activity occurred 4 to 8 weeks before the relapse when there were no apparent changes of the peripheral blood cell counts and bone marrow pictures. When relapsed, the cytostasis activity was markedly impaired. These results demonstrate that the assay of MNC cytostasis activity is a useful tool to predict or detect relapse of ALL at an earlier time. The cytostasis activity was still decreased after the cessation of chemotherapy for ALL, demonstrating a characteristic immunologic defect in ALL.

Studies on bone marrow and red cell enzymes (cholinesterase and ATPase) in Indian kala-azar.

In 31 kala-azar patients, the bone marrow picture and activities of three erythrocyte enzymes were studied: acetylcholinesterase (EC 3.1.1.7), pseudocholinesterase (EC 3.1.1.8) and ATPase (EC 3.6.1.3). The bone marrow was usually hypercellular with erythroid hyperplasia. The activities of these enzymes were similar to those in healthy individuals. The effect of treatment on the level of these enzymes was also followed.

胃癌摘出一年半後,左鎖骨上窩に形質細胞を主とする腫瘤と高γ-グロブリン血症をきたした一症例

A patient,77 years old male, who underwent partial gasterectomy due to gastric cancer at cardia (histologically: well-differentiated papillary adenocarcinoma (Photo.4), showing lymph node metastasis) in Dec.,1976, noticed one small tumor in his left supraclavicular region one and a half year thereafter, which had grown rapidly up to 5.0 x 5.5cm in Nov.,1978.Laboratory examinations (Tab.1, Fig.1) revealed anemia (249 x 104/mm3, mac rocytic normochromic)and polyclonal hypergammaglobulinemia (2.4g/dl,4O), although no plasma cell was found in his peripheral blood.As the biopsies of this tum or, carried out twice, showed a picture of non-specific chronic inflammation of the lymphnodi remarkably infiltrated with mature plasma cells (Photo.1), no tumor cells being found, it was difficult to rule out the plasma-cell type of Castleman's lymphoma.The bone marrow picture of the patient showed a slightly increased percentage of plasma cells.Gastroscopy and X-ray examination of the bones revealed no abnormalities. Because this tumor had continuously extended into the medi astinum, exstirpation could not be done; and anticancer drugs were not used, as no cancer cells were found anywhere.Thus, radiation and steroid therapies were performed against the plasma cell proliferation and hypergammaglobulinemia, resulting a decrease of the tumor size and a descent of the serum gammaglobulin level. But, after these therapies were stopped because of melena and decreased lymphocyte number, the tumor size began to increase again, the serum gammaglobulin level elevating up to 4.0g/dl (56 %) (Fig.1).The patient expired due to chachexia at the end of March,1979.The autopsy revealed in the tumor, considered to be swol len Virchow's node (Photo.2), undifferentiated carcinoma cells (Photo.3), probably originated from the gastric cancer previously resected, were found surrounded by immense plasma cell and lymphocyte proliferation.As to the interpretation of the cytological difference found between the cells of the primary focus and those of the Virchow's node, i. e. well-differentiated papillary adenocarcinoma and undifferentiated carcinoma respectively, the former cells might have been transformed into the latter through the influence of the anticancer drugs administered after the operation or that of the host immunity, or only the undifferentiated ones among the cancer cells existed in the primary focus might have metastasized.Besides, no carcinoma cell was found in the residual gastrium and, in the bone marrow, plasmacytosis was seen (Photo.5).The intensive plasma cell infiltra t ion concomitant with the metastatic cancer cells seen in the Virchow's node, the bone marrow plasmacytosis, and the hypergammaglobulinemia observed in this case could be interpreted as the signs of the immune response occurred in the cancer bearing host.Further, induction of plasmacytoma could be expected, if the immune stimulation as seen in this case persisted for a longer term.

Studies on hypoimmunoglobulinemia caused by unusual non-secretory plasmocytoma

The studies performed concerned the cause of severe infections and hypoimmunoglobulinemia observed in a 14 year old boy. The non-secretory plasmocytoma was detected. Data of immunological and other investigations are the subject matter of the paper. There were very low concentrations of serum IgA, IgM, IgG, IgE, not detectable IgD, and very low levels of chosen antibodies. Monoclonal protein and Bence-Jones protein were not found. Microscopic picture of bone marrow (using also immunofluorescent and electron-microscopy methods) was typical of the disease. The parameters of cellular immunity were normal.The investigations indicate the rare cause of acquired hypogamma-globulinemia in children and stress the necessity of its early diagnosis.

Accumulation of Orthochromatophilic Normoblasts in Bone Marrow of Vitamin E-deficient Monkey, Macaca fasicularis

Crab-eating monkeys, Macaca fasicularis, fed a vitamin E-depleted diet for over 15 months, showed signs of anemia manifested by a lowering in hematocrit, hemoglobin concentration and red blood cell number, and by an increased susceptibility of erythrocytes to hydrogen peroxide lysis. Bone marrow pictures indicated the presence of multinucleated erythroid precursor cells and an accumulation of orthochromatophilic normoblasts. Supplementation with vitamin E resulted in reticulocytosis and a return of the normal bone marrow picture.