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Non-malignant Haematological Disorders

Paroxysmal Nocturnal Haemoglobinuria
Idiopathic Thrombocytopenic Purpura (ITP)
Reactive Non-neoplastic Conditions
Iron Deficiency
Megaloblastic Anaemia
Anaemia of Chronic Disorders
Haemolytic Anaemia
Aplastic Anaemia
Metastatic Tumours
Neuroblastoma, Rhabdomyosarcoma, Ewing's and PNET

Paroxysmal Nocturnal Haemoglobinuria

Diagnosis of PNH is made by demonstrating the absence of GPI-anchored proteins by flow cytometry. For red cells deficiency of CD55 and CD59 should be shown, for granulocytes, deficiency of CD16, CD55, CD59 and/or CD66 should be shown. Expression of non GPI-linked proteins (red cells: Glycophorin A, and granulocytes: CD15) should be normal.

The size of the red cell and granulocyte PNH clones should be stated on the report. Further details of the size of the type III (complete deficiency) and type II (partial deficiency) red cell populations should be included. Follow up and regular monitoring of patients should be strongly recommended.

Idiopathic Thrombocytopenic Purpura (ITP)

Normal/increased numbers of morphologically normal megakaryocytes. Residual haemopoiesis should be normal, with no increase in blast cells or dysplastic features, although occasionally there may be some reactive lymphocytes present. A mild increase in eosinophils is usual.

Inadequate samples that are aparticulate remain the biggest problem, ideally assess the trephine biopsy.

Reactive Non-neoplastic Conditions

Increased haemopoiesis with no dysplastic features. No increase in blast cells. May be hypercellular.

Reactive lymphocytosis should be supported by flow cytometry.

Iron Deficiency

Iron stain shows the absence of iron stores (slide must be adequate with positive control). The erythroid series shows evidence of poor haemoglobinisation. Megakaryocytes may be increased, but appear normal. The myeloid series is morphologically normal. Iron studies must be recommended.

Megaloblastic Anaemia

Erythropoiesis may show marked megaloblastic changes that can be confused with erythrodysplasia. Expansion of the erythroid series with macrocytosis and nuclear-cytoplasmic asynchrony are characteristic. Megakaryocytes may be reduced. The myeloid series is abnormal with giant metamyelocytes and hyper-segmented neutrophils present. There should be no increase in myeloid blast cells.

Megaloblastic anaemia must be confirmed by B12 and folate assay.

Anaemia of Chronic Disorders

The marrow is usually cellular. There may be mild/moderate dyserythropoiesis, but the granulocytes and megakaryocytes are usually morphologically normal. Stainable iron is usually increased but ringed sideroblasts are not seen. The main differential diagnosis is usually MDS. The clinical context should be appropriate. This is a diagnosis of exclusion. The report should state the marrow is "compatible with anaemia of chronic disorders".

Haemolytic Anaemia

Relative or absolute erythroid hyperplasia is required to make this diagnosis, which should also fit the clinical context. In severe haemolytic anaemia of any cause there may be some dyserythropoiesis. An increase in mast cells should raise the possibility of PNH. A proportion of auto-immune haemolytic anaemias are associated with peripheral B-cell tumours, particularly Marginal Zone Lymphoma.

Aplastic Anaemia

Aplastic anaemia is defined as pancytopenia with a hypocellular marrow and no evidence of leukaemia. The trephine biopsy and a knowledge of the peripheral blood parameters as well as any preceding history (ie post chemotherapy) are required before a definitive diagnosis can be made. The bone marrow appearances are classically patchy and thus attempts to precisely quantitate the marrow cellularity should be made. When only a hypocellular bone marrow aspirate is present with other features of aplastic anaemia then the phrase "suggestive of aplastic anaemia which should be confirmed with a trephine biopsy" should be used. A request for a peripheral blood specimen to screen for PNH should be made in all cases (unless previously performed), and in children the possibility of Fanconi anaemia should be highlighted.

Metastatic Tumours

In all cases where the diagnosis of metastatic tumour is suspected in a bone marrow aspirate, it must be confirmed by immunocytochemistry.

If immunocytochemistry is inconclusive and there is no trephine biopsy the suspicion of metastatic disease can be raised in the report and further material requested, but a definitive diagnosis should not be made.

Neuroblastoma, Rhabdomyosarcoma, Ewing's and PNET

Cases that request an assessment of bone marrow involvement at either diagnosis or treatment follow up, will have flow cytometry and/or immunocytochemistry performed if indicated by morphological examination. Expected results in these cases are as follows:

Neuroblastoma: CD9⁺, CD56⁺, CD90⁺, CD99^-, CD34^-, CD45^-. Negative for Desmin, MyoD1 and Myogenin.
Ewing's/P.N.E.T.: CD9?, CD56⁺, CD90⁺, CD99⁺, CD34^-, CD45^-. Negative for Desmin, MyoD1 and Myogenin.
Rhabdomyosarcoma: CD9?, some CD56⁺, some CD90⁺, some CD99⁺, CD34^-, CD45^-. Positive for Desmin, MyoD1 and Myogenin.

Reports should comment on morphology and state either definite or suspected involvement.

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