Differentials

Acute myeloid leukaemias (AML)

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SIGNS / SYMPTOMS

Clinically, ALL and AML may be indistinguishable.

Skin infiltration and gum hypertrophy are more common in AML. Central nervous system, testis, and mediastinal involvement are more common in ALL.

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Bone marrow biopsy, peripheral blood smear, cytochemistry, and immunological markers can be used to establish the diagnosis.

In many cases, the leukaemic cells of AML or biphenotypic ALL are often poorly differentiated with minimal amount of cytoplasm. Morphologically, these cells are difficult to differentiate from those of ALL.[3][8]

The presence of myeloid markers and absence of lymphoid markers favours the diagnosis of AML. Scoring panels enable the diagnosis of biphenotypic leukaemia.

Lymphoblastic lymphoma (LBL)

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Clinically, ALL and LBL may be indistinguishable.

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Extramedullary involvement.

Bone marrow aspiration and trephine biopsy: lymphoblasts <25%.

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (MLNE)

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Clinically, ALL and blast phase MLNE may be indistinguishable.

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Full blood count: sustained/persistent eosinophilia.[71]

Biopsy: tissue eosinophilia.[71]

Serum tryptase: elevated.[71]

Presence of tyrosine kinase fusions (e.g., PDGFRA, PDGFRB, FGFR1, JAK2, ABL1, FLT3).[71][72]

Reactive lymphocytosis ('leukaemoid reaction')

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Infectious mononucleosis may present more commonly with pharyngitis, lymphadenopathy, and splenomegaly.

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Full blood count: abnormal lymphocytes; cytomegalovirus infection and Bordetella pertussis infection may present with significant lymphocytosis.[1][2]

Bone marrow aspiration and trephine biopsy: normal haematopoiesis.

Immunophenotyping may show increased numbers of haematogones (normal reactive B-cell progenitors).

Epstein-Barr virus serology: positive.

Viral testing: may be positive.

Culture of nasopharyngeal secretions: may be positive.

Small-cell lung cancer

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History of smoking, cough, hoarseness, dysphagia, haemoptysis, cachexia, and chest pain.

Clinical findings of clubbing or Horner syndrome.

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Chest x-ray: pulmonary mass.

Biopsy: small-cell lung cancer appears histologically as sheets of small round cells with dark nuclei, scant cytoplasm, fine granular nuclear chromatin, and indistinct nucleoli. In addition, immunohistochemical staining reveals positivity for chromogranin, neuron-specific enolase, and synaptophysin.

Merkel cell tumour

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Skin lesions, local lymphadenopathy, systemic symptoms suggesting dissemination (e.g., pulmonary or neurological symptoms).

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Biopsy: the Merkel cell exhibits immunocytochemical properties of both epithelial and neuroendocrine cells. Immunoreactivity for intermediate filaments such as the cytokeratins may differentiate Merkel cell from other undifferentiated tumours.

Rhabdomyosarcoma

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Disseminated disease can mimic ALL. There may be symptoms and signs suggesting primary site or other symptoms of metastatic disease (e.g., bone pain or respiratory symptoms).

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Rhabdomyosarcoma: immunohistochemical staining (IHC) or electron microscopy may provide evidence supporting myogenic differentiation. IHC can detect muscle-specific proteins.[30][48]

Aplastic anaemia

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Aplastic anaemia may resemble the aleukaemic pancytopenic subtype of ALL.

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Peripheral blood smear and bone marrow aspiration are helpful in differentiating diagnosis.

No blast cells in peripheral blood or bone marrow, and no leukoerythroblastic features.[30][48]

Bone marrow aspiration and biopsy are hypocellular in aplastic anaemia.

Immune thrombocytopenia (ITP)

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Childhood ITP may resemble the aleukaemic pancytopenic subtype of ALL.

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Peripheral blood smear and bone marrow aspiration are helpful in differentiating diagnosis.

No blast cells in peripheral blood or bone marrow, and no leukoerythroblastic features.[30][48]

Bone marrow aspiration and biopsy are normocellular in ITP with preservation of all three lineages.

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