eMedicine Specialties > Hematology > Stem Cells and Disorders

Lymphoma, Malignant Anaplastic (Ki 1+): Differential Diagnoses & Workup

Author: Delong Liu, MD, PhD, Associate Professor of Medicine, Division of Oncology/Hematology, New York Medical College; Chief of Hematology, Phelps Memorial Hospital Center; Director of Non-ablative Allogeneic Stem Cell Transplantation Program, Westchester Medical Center; Editor-in-Chief, Journal of Hematology and Oncology
Coauthor(s): Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University; Christine Urbanski, MD, Consulting Staff, Hematology/Oncology Associates, RMH Regional Cancer Center
Contributor Information and Disclosures

Updated: Dec 12, 2008

Differential Diagnoses

Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Diffuse Large Cell

Other Problems to Be Considered

Lymphomatoid papulosis
Malignant histiocytosis
Metastatic carcinoma
Metastatic melanoma

Workup

Laboratory Studies

  • The necessary imaging and laboratory tests to appropriately evaluate a patient who may have anaplastic large cell lymphoma (ALCL) are similar to those recommended in the standard evaluation of aggressive non-Hodgkin lymphomas and are described briefly, as follows:
    • Hematology: Complete blood cell (CBC) count, peripheral smear review, and bone marrow aspiration and biopsy are standard.
    • Chemistry: Electrolyte evaluations, renal function studies, liver function tests and liver-associated enzyme tests, and uric acid evaluations are appropriate. Serum lactic dehydrogenase (LDH), beta2-microglobulin, and albumin values are useful for prognostic categorization. The LDH and beta2-microglobulin levels also serve as indirect indicators of tumor burden and proliferative activity.
    • Absolute lymphocyte count (ALC) has been reported to be an independent prognostic factor.15 ALC <1000/μ L correlates with shorter survival and lower complete remission rate.

Imaging Studies

  • Chest radiographs are used to assess for lymphadenopathy, pleural effusions, and parenchymal lesions.
  • Computed tomography (CT) scans of the chest, abdomen, and pelvis should be performed, with close attention to lymphadenopathy, pleural effusions, pulmonary parenchymal lesions, splenomegaly, and hepatic and splenic filling defects.
  • Ultrasonography of the liver is indicated in patients who have abnormal results from laboratory liver function tests and normal hepatic imaging findings on CT scan images.
  • Gallium scans, although not as useful in the initial staging workup, can be helpful for evaluating the response to treatment, because continued positive uptake in a residual mass after completion of treatment is an indicator of persistent disease.
  • Magnetic resonance imaging (MRI) can be useful for detecting occult bone marrow lymphoma involvement, which is displayed as patchy distribution and, thus, will be missed on bone marrow biopsy findings. A spinal study is indicated for patients with epidural involvement and possible spinal cord compression.
  • A bone scan is indicated if musculoskeletal symptoms are present or if the alkaline phosphatase level is elevated.
  • Positron emission tomography (PET) scanning is gaining wider approval as a potential staging modality at both diagnosis and relapse of cases of anaplastic large cell lymphoma (ALCL).

Procedures

  • Excisional biopsy of lymphadenopathy is necessary to confirm the diagnosis of anaplastic large cell lymphoma (ALCL). Critical assessments of cell morphology, lymph node architecture, immunophenotype, and molecular and cytogenetic analyses are indicated.
  • Bone marrow aspiration and biopsy are performed to search for occult lymphoma involvement.
  • Immunophenotyping and immunohistochemistry study of the lymphoma cells is critical in the definitive diagnosis of anaplastic large cell lymphoma (ALCL). The major features of the ALCL immunophenotype typically include CD30+, CD15 –, and CD45+. (Hodgkin lymphoma typically expresses CD30+ and CD15+.) Sixty percent of cases express one or more T-cell antigens (CD3+, CD43, or CD45RO). ALK protein may be detected in most cases (60-70%) by immunohistochemistry.

Histologic Findings

The morphology of anaplastic large cell lymphoma (ALCL) is similar within its major clinical subforms, the primary systemic and cutaneous varieties. The tumor cells are usually large, with abundant cytoplasm. They manifest prominent nucleoli, display an eccentrically located and pleomorphic nucleus that is often kidney-shaped, and tend to infiltrate lymph nodes in a sinusoidal and paracortical pattern.1

The malignant cells stain positive for the CD30 antigen, a very sensitive but nonspecific test result that is also positive in other lymphomas, including Hodgkin disease. Most cases exhibit either T-cell or null phenotype, with frequent CD3 expression, cytotoxic protein expression, clonal T-cell receptor gene rearrangements by polymerase chain reaction (PCR), and lack of B cell – associated markers.16 The primary systemic form, unlike the primary cutaneous form, generally stains positive for EMA and usually displays the t(2;5) translocation and the chimeric p80 protein with PCR and antibody studies.

Staging

The Cotswold modification of the Ann Arbor staging system is the standard anatomic staging system for non-Hodgkin lymphoma and Hodgkin disease, and it is used to evaluate the extent of disease in patients with anaplastic large cell lymphoma (ALCL). Accurate staging allows appropriate therapeutic selection and contributes to predicting the prognosis. Staging for anaplastic large cell lymphoma (ALCL) is as follows1,11 :

  • Stage I – Involvement of a single lymph node region or lymphoid structure
  • Stage II – Involvement of 2 or more lymph node regions on the same side of the diaphragm
  • Stage III – Involvement of lymph node regions or structures on both sides of the diaphragm
  • Stage IV – Involvement of extranodal sites beyond that designated as E (see below)
  • Further staging designations include the following:
    • Suffix A – No symptoms (any disease stage)
    • Suffix B – Fever (temperature >38 º C); drenching sweats; unexplained weight loss (eg, 10% of body weight within preceding 6 mo) (any disease stage)
    • Suffix E – Involvement of a single extranodal site that is contiguous or proximal to the known nodal site (stages I-III)
  • Cotswold modifications are as follows:
    • Suffix X – Denotes bulky disease (a widening of the mediastinum by more than one third or the presence of a nodal mass with a maximal dimension of >10 cm)
    • Subscripts – Used to indicate the number of anatomic regions
    • Stage III subdivisions – May be subdivided to include III(1), with or without splenic, hilar, celiac, or portal nodes, and III(2), with para-aortic, iliac, or mesenteric nodes
    • Further identification – Staging identified as clinical stage (CS) or pathologic stage (PS)

More on Lymphoma, Malignant Anaplastic (Ki 1+)

Overview: Lymphoma, Malignant Anaplastic (Ki 1+)
Differential Diagnoses & Workup: Lymphoma, Malignant Anaplastic (Ki 1+)
Treatment & Medication: Lymphoma, Malignant Anaplastic (Ki 1+)
Follow-up: Lymphoma, Malignant Anaplastic (Ki 1+)
References
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References

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  2. Rodriguez J, Pugh W, Romaguera J, Cabanillas F. Anaplastic Ki-1 + large-cell lymphoma. Cancer Invest. 1993;11(5):554-8. [Medline].

  3. Stein H, Foss HD, Durkop H, et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood. Dec 1 2000;96(12):3681-95. [Medline]. [Full Text].

  4. Zinzani PL, Bendandi M, Martelli M, et al. Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients. J Clin Oncol. Mar 1996;14(3):955-62. [Medline].

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  6. Lamant L, de Reynies A, Duplantier MM, et al. Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes. Blood. Mar 1 2007;109(5):2156-64. [Medline]. [Full Text].

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  10. Pugh WC, McBride JA. The pathologic basis for the classification of non-Hodgkin lymphomas. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:1263-93.

  11. van Besien K, Cabanillas F. Clinical manifestations, staging, and treatment of non-Hodgkin lymphoma. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:1293-339.

  12. Beljaards RC, Kaudewitz P, Berti E, et al. Primary cutaneous CD30-positive large cell lymphoma: definition of a new type of cutaneous lymphoma with a favorable prognosis. A European Multicenter Study of 47 patients. Cancer. Mar 15 1993;71(6):2097-104. [Medline].

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Further Reading

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Keywords

malignant anaplastic lymphoma, Ki-1+ anaplastic lymphoma, anaplastic large-cell lymphoma, Ki-1 lymphoma, CD30+, ALCL, anaplastic lymphoma kinase-positive lymphoma, ALK-positive lymphoma, anaplastic Ki-1+ large cell lymphoma, lymphoma, large cell anaplastic CD30+ Ki-1 lymphoma, Ki-1 large cell lymphoma, cutaneous and nodal Ki-1 positive anaplastic large cell lymphoma, cutaneous lymphoma, skin cancer, cancer, extranodal lymphoma, extra-nodal lymphoma, systemic lymphoma, systemic cancer, anaplastic lymphoma, systemic anaplastic large-cell lymphoma

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Contributor Information and Disclosures

Author

Delong Liu, MD, PhD, Associate Professor of Medicine, Division of Oncology/Hematology, New York Medical College; Chief of Hematology, Phelps Memorial Hospital Center; Director of Non-ablative Allogeneic Stem Cell Transplantation Program, Westchester Medical Center; Editor-in-Chief, Journal of Hematology and Oncology
Delong Liu, MD, PhD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Koyamangalath Krishnan, MD, FRCP, FACP, Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, James H Quillen College of Medicine at East Tennessee State University
Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians
Disclosure: Nothing to disclose.

Christine Urbanski, MD, Consulting Staff, Hematology/Oncology Associates, RMH Regional Cancer Center
Christine Urbanski, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

David Aboulafia, MD, Medical Director, Bailey-Boushay House; Clinical Professor, Department of Medicine, Division of Hematology, University of Washington
David Aboulafia, MD is a member of the following medical societies: American College of Physicians, American Medical Association, American Medical Directors Association, American Society of Hematology, Infectious Diseases Society of America, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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