Differentials
Acute myeloid leukemias (AML)
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.
INVESTIGATIONS
Bone marrow biopsy, peripheral blood smear, cytochemistry, and immunologic markers can be used to establish the diagnosis.
In many cases, the leukemic 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 favors the diagnosis of AML. Scoring panels enable the diagnosis of biphenotypic leukemia.
Lymphoblastic lymphoma (LBL)
SIGNS / SYMPTOMS
Clinically, ALL and LBL may be indistinguishable.
INVESTIGATIONS
Extramedullary involvement.
Bone marrow aspiration and trephine biopsy: lymphoblasts <25%.
Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes (MLNE)
SIGNS / SYMPTOMS
Clinically, ALL and blast phase MLNE may be indistinguishable.
Reactive lymphocytosis ("leukemoid reaction")
SIGNS / SYMPTOMS
Infectious mononucleosis may present more commonly with pharyngitis, lymphadenopathy, and splenomegaly.
INVESTIGATIONS
Complete blood count: abnormal lymphocytes; cytomegalovirus infection and Bordetella pertussis infection may present with significant lymphocytosis.[1][2]
Bone marrow aspiration and trephine biopsy: normal hematopoiesis.
Immunophenotyping may show increased numbers of hematogones (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
SIGNS / SYMPTOMS
History of smoking, cough, hoarseness, dysphagia, hemoptysis, cachexia, and chest pain.
Clinical findings of clubbing or Horner syndrome.
INVESTIGATIONS
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 tumor
SIGNS / SYMPTOMS
Skin lesions, local lymphadenopathy, systemic symptoms suggesting dissemination (e.g., pulmonary or neurologic symptoms).
INVESTIGATIONS
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 tumors.
Rhabdomyosarcoma
SIGNS / SYMPTOMS
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).
Aplastic anemia
SIGNS / SYMPTOMS
Aplastic anemia may resemble the aleukemic pancytopenic subtype of ALL.
Immune thrombocytopenia (ITP)
SIGNS / SYMPTOMS
Childhood ITP may resemble the aleukemic pancytopenic subtype of ALL.
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