A 50-year-old Iraqi man presented with splenomegaly and pyrexia of unknown origin. A bone marrow aspirate was done as part of the investigations and unexpectedly showed Plasmodium falciparum parasites. Malaria had not been suspected as this condition is now rare in Iraq but it subsequently transpired that the patient had recently visited Pakistan.The gametocytes that are observed in the bone marrow differ from those that are observed in the blood, being less mature [1]. The immature gametocytes that are seen include some that are sail-shaped, spindle-shaped or oval (top) rather than the crescent-shaped macrogametocyte and sausage-shaped microgametocyte that are usually observed in the blood. This reflects the fact that gametocytes develop in the internal organs, including the bone marrow, rather than in the circulating blood. Photographs of the bone marrow of this patient show sail-shaped (left), spindle-shaped (centre) and oval (right) immature gametocytes. Some mature gametocytes were also present.
A 4-year-old boy presented with pallor, visual problems and recurrent multiple bilateral renal stones that had been unresponsive to (non-specific) medical treatment. He had seen a number of physicians over a period of two years without a diagnosis being made. He was found to have pancytopenia, the blood count showing: white cell count 3.1 3 10 9 /l, hemoglobin concentration 86 g/l, and platelet count 102 3 10 9 /l. A bone marrow aspirate was performed to investigate the pancytopenia and revealed numerous clear cystine crystals, apparently free and within macrophages (images). This rare lysosomal storage disease is readily diagnosed from a bone marrow aspirate because of the presence of distinctive non-staining crystals. The crystals have straight edges and, when seen end on, are hexagonal (lower image).
Diagnosis of acute leukemia in Iraq is mainly dependent on the personal experience of the laboratory physician. Local guidelines in this field were never proposed and the international guidelines are very difficult to apply as the only available techniques include morphology of peripheral blood and bone marrow specimens plus very limited immunohistochemistry CD markers and PCR testing for BCR-ABL oncogene only, therefore the aim for diagnosis, classification and subclassification of acute leukemia in this country should be that of diagnosis and lineage assignment that serves a clear therapeutic goal.Having been working in the field of laboratory hematology since 2003 in the major teaching hospitals in Baghdad, I found that the following scheme is the available useful option:Acute leukemia should be classified on the basis of FAB group, but using a cut-off point of 20% blast cells, as proposed in the WHO classification [1]. Acute myeloid leukemiaWith Romanowsky stain morphology AML-M2, M3, M4, M5b and M6 can be recognized readily.By adding few special stains such as Sudan black B (SBB) [2] (and not myeloperoxidase as SBB has a little more sensitivity in detecting myeloblasts which is the crucial point), plus a non-specific esterase stain as -naphthyl acetate esterase it becomes possible to recognize AML-M1 and most cases of AML-M5a [3].The AML cases that cannot be distinguished by morphology and cytochemistry, specifically M0 and M7, for which the presence of myeloid dysplasia in the former and the cytoplasmic blebs in the latter may give a hint for the probable diagnosis, however there is still the need for more positive diagnostic technique and as the flow cytometry immunophenotyping is not available then the use of a limited number of CD markers study by immunohistochemistry to identify the lineage of acute leukaemia is the option, these include CD33, anti-myeloperoxidase and CD41.Rare types of AML like M5c require high degree of morphology experience, in which malignant cells appearance is reminiscent of tissue histiocytes [4].There is still a small proportion of cases that would be only certainly diagnosed after the response to treatment as in rare forms of AML-M3v [5].
A variety of types of inclusions are seen in the neoplastic cells of multiple myeloma (plasma cell myeloma). Among these, crystalline inclusions resembling Auer rods are uncommon. This 47-year-old Iraqi woman presented with back pain and anemia (haemoglobin concentration 100 g/l). A diagnosis of immunoglobulin (Ig) Gj myeloma with Bence-Jones proteinuria was made [1]. The bone marrow was heavily infiltrated by cytologically abnormal plasma cells including multinucleated and nucleolated cells (left). In addition the majority of neoplastic cells contained azurophilic cytoplasmic crystals. A further curious feature (right) was the presence of mitotic figures within crystal-containing myeloma cells, the presence of the crystals serving to identify the cells in mitosis as myeloma cells.Auer-rod like inclusions in myeloma cells have been described in association with IgG, IgA, IgM and light chain only (kappa) myeloma[2]. They are generally[2], but not invariably [3], associated with paraproteins with kappa light chains and are more often associated with IgA myeloma. They do not represent immunoglobulin but rather are of lysosomal origin, being positive for alpha naphthyl acetate esterase, beta glucuronidase and acid phosphatase [4]. There is an association with adult Fanconi syndrome due to deposition of crystals in renal tubules [2]. Myeloma cells can also contain crystalline inclusions that do represent immunoglobulin but these differ from Auer-rod like inclusions in that they stain pale pink on Romanowsky stains, rather than being azurophilic.
According to the WHO classification of acute leukemia, diagnosis is based on an arbitrary cut-off point of 20% blasts, as the percentage of bone marrow total or non-erythroid cells, or as the percentage of peripheral blood cells. This cut-off point is also currently used in under-resourced laboratories in which the FAB classification is more commonly used.This cut-off point seems to be universally accepted, and for the time being represents the bestknown criterion for defining acute leukemia; however, "arbitrary" may still precede the criterion due to the follow:1. This percentage does not represent a specific biological event in the continuum of an increasing blast count, but is merely, to the best to our knowledge, a cut-off point that facilitates relatively clear classification and therapeutic planning. Nonetheless, some high-risk MDS patients with only 10% bone marrow blasts are actively treated. 2. A significant difference in the blast percentage cut-off point between peripheral blood and bone marrow is well established in MDS; RAEB-1 (blast count <5% in peripheral blood and 5%-9% in bone marrow) and RAEB-2 (blast count of 5%-9% in peripheral blood and 10%-19% in bone marrow). In acute leukemia no such differentiation exits. 3. Morphological findings of pathological "clonal" blasts (type II that contain Auer rods, PseudoChédiak-Higashi or other specific inclusions that are not seen in reactive marrow) refer to the diagnosis of RAEB-2 or AML; here again the arbitrary cut-off point of 20% blasts results in a specific diagnosis. 4. The original FAB classification was based for many years on the arbitrary cut-off point of 30% bone marrow blasts and in the past some patients with 20%-29% blasts remained stable for months without chemotherapy. 5. Although there is a general consensus concerning the criterion for identifying myeloblasts as agranular (type I) and granular blasts (types II and III), there is some disagreement concerning their definitions, and in practice it may be a matter of convention (subjective method) to differentiate them from the continuum of cells, such as determining whether the cell is a type III blast or a promyelocyte. 6. Blasts refer to myeloblasts, lymphoblasts, monoblasts, promonocytes, and megakaryoblasts.
An 8-year-old Iraqi male presented with fever and pallor of 2-months duration. There was no lymphadenopathy, splenomegaly or hepatomegaly. A full blood count showed: hemoglobin concentration 6.9 g/dl, white blood cell count 1.5 3 10 9 /l and platelet count 217 3 10 9 /l. Examination of a bone marrow aspirate showed acute myeloid leukemia (AML) with little maturation; blast cells were 85% of nucleated cells, and the case was classified as FAB (French-American-British) M1 AML. An unusual feature was the presence not only of Auer rods (left) but also of pseudo-Ché diak-Higashi inclusions, which on a Romanowsky stain varied from pink to deep purple (right). In addition to typical thin Auer rods there were also thick rodshaped inclusions (left and right).Pseudo-Ché diak-Higashi inclusions are observed occasionally in AML 1 (including acute promyelocytic leukemia) and also, rarely, in refractory anaemia with excess of blasts. 2 The inclusions are formed by fusion of azurophilic (primary) granules and show myeloperoxidase activity and Sudan black B staining. On ultrastructural examination they are heterogeneous and, in contrast to the inclusions seen in the inherited anomaly, contain rod-shaped structures showing periodicity. 1 The diagnostic significance of these inclusions is likely to be similar to that of Auer rods, indicating either AML or a high grade myelodysplastic syndrome.
This composite photograph is of the peripheral blood of a 16-year-old Iraqi girl presenting with mild hepatosplenomegaly, generalized bruising and rectal bleeding. A blood count showed a white cell count of 17 3 10 9 /l, hemoglobin concentration 2.5 g/dl and platelet count 7 3 10 9 /l. A peripheral blood film made without delay showed blast cells of unusual morphology, many having striking nuclear lobulation (top); nucleoli were prominent. Some blast cells contained Auer rods or granules, confirmed on Sudan black B staining (bottom left and bottom right). Maturing myeloid cells were dysplastic. A diagnosis of acute myeloid leukemia with differentiation was made, FAB (French-American-British) M2 AML.Lobulated promonocytes are characteristic of acute monocytic leukemia and lobulated promyelocytes are similarly typical of the variant microgranular form of acute promyelocytic leukemia. However pronounced symmetrical nuclear lobulation of myeloblasts, as shown in this patient, is a quite uncommon feature of AML.
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