eMedicine Specialties > Ophthalmology > Hematologic & Cardiovascular Disorders

Leukemias: Differential Diagnoses & Workup

Author: Lihteh Wu, MD, Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica
Coauthor(s): Teodoro Evans, MD, Retina Fellow, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica; Joaquin Martinez, MD, Consulting Staff, Department of Ophthalmology, Hospital Nacional de Ninos and Clinica Dr. Clorito Picado; Director of Retinal and Vitreous Clinic at Hospital Nacional de Ninos; Consulting Staff in Ultrosonography and Angiography, Clinica Oftalmologica Costarricense; Private Practice, San Rafael de Escazu, San Jose, Costa Rica
Contributor Information and Disclosures

Updated: Jul 20, 2007

Differential Diagnoses

Cellulitis, Orbital
Central Retinal Vein Occlusion

Other Problems to Be Considered

Rhabdomyosarcoma
Metastatic neuroblastoma
Hyperviscosity retinopathy
Childhood iritis

Workup

Laboratory Studies

  • CBC and differential

    • CBC is the most useful initial laboratory test in patients suspected of having leukemia. Most patients will show some abnormality in the CBC and some blasts will be seen in the peripheral smear in patients with acute leukemias.
    • To diagnose CLL, a lymphocytosis of greater than 5000/mm3 must be present. The absolute neutrophil count is usually normal and red blood cell counts and platelet counts are mildly decreased. In addition, the peripheral smear or bone marrow should show normal mature small lymphocytes with less than 55% atypical or blast forms.
    • CML is defined by its peripheral WBC count. Typically, leukocytosis is in excess of 100,000/mm3. The differential count shows that neutrophil precursors are present. This is accompanied by basophilia and eosinophilia. Unlike those in AML, these cells are mature and functional.
  • Bone marrow aspiration

    • Bone marrow aspiration establishes the diagnosis of leukemia. The morphology of blasts usually can differentiate between ALL and AML.
    • In ALL, a homogeneous infiltrate of lymphoblasts replaces the normal bone marrow elements. Lymphoblasts usually are small and measure approximately 14 µm in diameter. They have scant cytoplasm with no granules. The nucleus has no nucleoli or a small indistinct one.
    • For the diagnosis of AML, 30% of the nucleated cells in the aspirate must be blast cells of myeloid origin. Multiple large nucleoli, delicate chromatin, gray-blue cytoplasm, and Auer rods characterize myeloblasts. The presence of Auer rods is virtually diagnostic of AML, because these condensed lysosomal cytoplasmic azurophilic rod-shaped structures do not appear in ALL.
    • In CLL, bone marrow infiltration exceeds 30% lymphocytes. The lymphocytes are mature with less than 55% atypical or blast forms. The nuclei are round, cytoplasm is scant, chromatin is compact, nucleoli are inconspicuous, and mitotic figures are rare.
  • Immunophenotyping
    • Immunophenotyping using multiparameter flow cytometry following labeling with monoclonal antibodies to cell-surface antigens identifies the B or T cell origin of the lymphoblasts.
    • Based on the expression of B lineage-restricted antigens and clonal rearrangements of immunoglobulin heavy and light chain genes, it has been estimated that up to 80% of ALL cases arise from B-cell precursors. The majority possesses a common ALL antigen (CALLA) that is present only on leukemic cells.
    • T-cell ALL possesses receptors for sheep erythrocytes, and, when these are combined, they form E-rosettes.
    • A final subset of ALL lacks B- or T-cell characteristics and is referred to as null-cell ALL. 
    • Certain myeloid-specific antigens, such as CD13, CD33, and CD41, have been used to diagnose AML. 
    • The malignant cells in CLL correspond to a minor subpopulation of B cells that express cell surface immunoglobulin M (IgM) and immunoglobulin D (IgD) and the T-cell associated antigen CD5.
  • Histochemical stains
    • Histochemical stains for myeloperoxidase (Leder stain) and nonspecific esterase have a strong affinity for myelogenous precursors but fail to stain lymphocytic forerunners.
    • Demonstration of nuclear DNA polymerizing enzyme terminal deoxynucleotidyl transferase (TdT) is indicative of a lymphoid origin. However, up to 2-5% of patients with AML exhibit this enzyme. Exceptions may occur when a malignant clone arises from multipotent cells that may express both myelogenous characteristics and lymphocytic characteristics.
  • Chromosomal analysis

    • Chromosomal analysis also plays an important role. The diagnosis of CML is established by identifying cytogenetically or molecularly a clonal expansion of a hematopoietic stem cell possessing a reciprocal translocation between chromosomes 9 and 22.
    • Chromosomal analysis of the leukemic cell currently provides the most important pretreatment prognostic information in AML.

Imaging Studies

  • Fluorescein angiography may reveal myriad diffuse leakage points at the level of the RPE. This pattern also may be seen in Vogt-Koyanagi-Harada disease, diffuse choroidal melanoma, metastatic tumors, and posterior scleritis.
  • Optical coherence tomography (OCT) can help confirm the diagnosis of macular exudative detachment. OCT can also be useful in monitoring patients following treatment.

Histologic Findings

Histopathological studies have shown the choroid to be the ocular structure most commonly involved by leukemia. The choroid is thickened, especially at the posterior pole. The RPE may be hyperplastic, atrophied, or hypertrophied. Photoreceptor loss, drusen formation, serous detachment, and cystoid retinal edema may be present.

Immature white blood cells infiltrate the retina, and, when they accumulate, nodular masses may be seen. The retinal vessels usually are packed with immature leukocytes. Capillary nonperfusion may result due to massive accumulation of cells. Diffuse infiltration of the iris and the ciliary body is commonly seen. The infiltrates are usually denser near the sphincter and the base of the iris. The trabecular meshwork may be clogged with leukemic cells leading to glaucoma.

Histopathological studies indicate that leukemic infiltration in the orbit most often was mild and diffuse as opposed to massive and tumorous. A chloroma of the orbit is composed of immature granulocyte cells, which contain large amounts of the enzyme myeloperoxidase, giving the tumor a greenish hue on gross examination. Because of the poorly differentiated nature of this tumor on histological examination and often unremarkable CBC, it may be misdiagnosed as a lymphoma.

Histological diagnosis of lymphoma in a rapidly growing orbital mass of a child is unlikely because orbital lymphomas in children are quite rare.

More on Leukemias

Overview: Leukemias
Differential Diagnoses & Workup: Leukemias
Treatment & Medication: Leukemias
Follow-up: Leukemias
Multimedia: Leukemias
References
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Further Reading

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Keywords

leukemic retinopathy, acute myelogenous leukemia, AML, acute lymphocytic leukemia, ALL, chronic myelogenous leukemia, CML, chronic lymphocytic leukemia, CLL

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Contributor Information and Disclosures

Author

Lihteh Wu, MD, Consulting Surgeon, Department of Ophthalmology, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica
Lihteh Wu, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Association for Research in Vision and Ophthalmology, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Coauthor(s)

Teodoro Evans, MD, Retina Fellow, Vitreo-Retinal Section, Instituto De Cirugia Ocular, Costa Rica
Disclosure: Nothing to disclose.

Joaquin Martinez, MD, Consulting Staff, Department of Ophthalmology, Hospital Nacional de Ninos and Clinica Dr. Clorito Picado; Director of Retinal and Vitreous Clinic at Hospital Nacional de Ninos; Consulting Staff in Ultrosonography and Angiography, Clinica Oftalmologica Costarricense; Private Practice, San Rafael de Escazu, San Jose, Costa Rica
Joaquin Martinez, MD is a member of the following medical societies: Costa Rican Ophthalmology Association
Disclosure: Nothing to disclose.

Medical Editor

Andrew W Lawton, MD, Medical Director of Neuro-Ophthalmology Service, Section of Ophthalmology, Baptist Eye Center, Baptist Health Medical Center
Andrew W Lawton, MD is a member of the following medical societies: American Academy of Ophthalmology, Arkansas Medical Society, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Brian R Younge, MD, Professor of Ophthalmology, Mayo Clinic School of Medicine
Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society
Disclosure: Nothing to disclose.

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

 
 
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