eMedicine Specialties > Pediatrics: General Medicine > Oncology

Lymphoproliferative Disorders: Differential Diagnoses & Workup

Author: Stuart S Winter, MD, Associate Professor, Department of Pediatrics, University of New Mexico Health Sciences Center
Contributor Information and Disclosures

Updated: Nov 24, 2009

Differential Diagnoses

Non-Hodgkin Lymphoma

Other Problems to Be Considered

Castleman disease
Lymphomatoid papulosis
Anaplastic large cell lymphoma

Workup

Laboratory Studies

  • General tests in lymphoproliferative disorders (LPDs)
    • Clinical findings indicate local or distant adenopathy and hepatosplenomegaly.
    • In certain conditions, the GI tract or lung tissue may also be affected.
  • Biochemical panel
    • Perform serologic tests for cytomegalovirus and Epstein-Barr virus (EBV).
    • Measure the erythrocyte sedimentation rate.
    • Evaluate electrolyte, BUN, creatinine, phosphate, calcium, and uric acid levels to rule out tumor lysis syndrome.
    • Assess lactate dehydrogenase levels to assess the neoplastic burden.

Imaging Studies

  • Radiography
    • CT scans obtained with intravenous or oral contrast material can help in determining the true extent of abdominal adenopathy, infiltration of the bowel wall, and the accurate sizes of tumorous masses. This information is important for staging and assessing therapeutic response. For example, the CT scan in the image below reveals parenchymal nodularities.

    • Parenchymal nodularities.

      Parenchymal nodularities.

      [ CLOSE WINDOW ]
      Parenchymal nodularities.

      Parenchymal nodularities.

    • MRI studies of soft-tissue infiltrative processes can refine the clinician's understanding of the tumor burden and the potential that vital structures might be compromised.
    • Chest radiography is performed in patients with pulmonary lesions to follow the progression or regression of disease. In some patients, pulmonary functional tests can provide further objective evidence of disease progression or a therapeutic response.
  • Bone scanning
  • Ultrasonography: Ultrasonography is sometimes helpful.
  • Small bowel follow-through study: In children with GI lesions, this test helps in diagnosing ileal disease.

Other Tests

  • As with all neoplastic processes, "the tissue is the issue." In rapidly growing tumors, areas of necrotic tissue may complicate morphologic use of fine-needle aspirates.
  • EBV detection by means of Southern blot hybridization or polymerase chain reaction (PCR) can be helpful. The in situ hybridization of the EBV-encoded RNA (EBER) test has become a useful adjunct in the diagnosis of EBV-related lymphoproliferative disorders.

Procedures

  • Examination of the bone marrow may help in differentiating metastatic disease from other diseases.
  • Diagnostic spinal tap is used in children with primary tumors involving the head or neck region to exclude spread to the neuraxis.
  • Surgical resection does not play an important role in the control of lymphoproliferative disorders. Most lymphoproliferative tumors are not easily resectable and, given the underlying nature of the affected cell type, rapid lymphatic spread to distant sites is common.

Histologic Findings

  • Important histologic findings often include an amorphous oligoclonal or monoclonal population of immature-appearing lymphocytes. Histologic samples tend to show either polymorphic or monomorphic infiltrates of lymphocytes.
  • In most cases, flow cytometric and cytogenetic analyses show polyclonal populations of B cells or T cells without cytogenetic abnormalities. These features can distinguish lymphoproliferative disorders from true malignancies, which frequently show monoclonal cell populations and acquired cytogenetic abnormalities. However, the cell morphology occasionally mimics specific malignant lymphomas, such as Hodgkin disease or Burkitt lymphoma.

More on Lymphoproliferative Disorders

Overview: Lymphoproliferative Disorders
Differential Diagnoses & Workup: Lymphoproliferative Disorders
Treatment & Medication: Lymphoproliferative Disorders
Follow-up: Lymphoproliferative Disorders
Multimedia: Lymphoproliferative Disorders
References
[ CLOSE WINDOW ]

References

  1. Spector BD, Perry GS III, Kersey JH. Genetically determined immunodeficiency diseases (GDID) and malignancy: report from the immunodeficiency--cancer registry. Clin Immunol Immunopathol. Sep 1978;11(1):12-29. [Medline].

  2. Engel P, Eck MJ, Terhorst C. The SAP and SLAM families in immune responses and X-linked lymphoproliferative disease. Nat Rev Immunol. Oct 2003;3(10):813-21. [Medline].

  3. Latour S. Natural killer T cells and X-linked lymphoproliferative syndrome. Curr Opin Allergy Clin Immunol. Dec 2007;7(6):510-4. [Medline].

  4. Worth A, Thrasher AJ, Gaspar HB. Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. Br J Haematol. Apr 2006;133(2):124-40. [Medline].

  5. Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. Jan 2008;15(1):22-9. [Medline].

  6. Notarangelo LD, Miao CH, Ochs HD. Wiskott-Aldrich syndrome. Curr Opin Hematol. Jan 2008;15(1):30-6. [Medline].

  7. Ohta H, Fukushima N, Ozono K. Pediatric post-transplant lymphoproliferative disorder after cardiac transplantation. Int J Hematol. Sep 2009;90(2):127-36. [Medline].

  8. Baehner RL. Lymphocytes. In: Miller DR, Baehner RL, eds. Blood Diseases in Infancy and Childhood. St. Louis, MO: CV Mosby; 1990:578-603.

  9. Bird AG, Britton S. The relationship between Epstein-Barr virus and lymphoma. Semin Hematol. Oct 1982;19(4):285-300. [Medline].

  10. Brusamolino E, Pagnucco G, Bernasconi C. Secondary lymphomas: a review on lymphoproliferative diseases arising in immunocompromised hosts: prevalence, clinical features and pathogenetic mechanisms. Haematologica. Nov-Dec 1989;74(6):605-22. [Medline].

  11. Certain S, Barrat F, Pastural E, et al. Protein truncation test of LYST reveals heterogenous mutations in patients with Chediak-Higashi syndrome. Blood. Feb 1 2000;95(3):979-83. [Medline].

  12. Craig FE, Gulley ML, Banks PM. Posttransplantation lymphoproliferative disorders. Am J Clin Pathol. Mar 1993;99(3):265-76. [Medline].

  13. Fiorilli M, Carbonari M, Crescenzi M, et al. T-cell receptor genes and ataxia telangiectasia. Nature. Jan 17-23 1985;313(5999):186. [Medline].

  14. Kempf W. CD30+ lymphoproliferative disorders: histopathology, differential diagnosis, new variants, and simulators. J Cutan Pathol. Feb 2006;33 Suppl 1:58-70. [Medline].

  15. Locker J, Nalesnik M. Molecular genetic analysis of lymphoid tumors arising after organ transplantation. Am J Pathol. Dec 1989;135(6):977-87. [Medline].

  16. Loughrey M, Trivett M, Lade S, et al. Diagnostic application of Epstein-Barr virus-encoded RNA in situ hybridisation. Pathology. Aug 2004;36(4):301-8. [Medline].

  17. Lundell R, Elenitoba-Johnson KS, Lim MS. T-cell posttransplant lymphoproliferative disorder occurring in a pediatric solid-organ transplant patient. Am J Surg Pathol. Jul 2004;28(7):967-73. [Medline].

  18. Marti GE, Rawstron AC, Ghia P, et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol. Aug 2005;130(3):325-32. [Medline].

  19. Nichols KE. X-linked lymphoproliferative disease: genetics and biochemistry. Rev Immunogenet. 2000;2(2):256-66. [Medline].

  20. Rigaud S, Fondaneche MC, Lambert N, et al. XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature. Nov 2 2006;444(7115):110-4. [Medline].

  21. Sanal O, Wei S, Foroud T, et al. Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region. Am J Hum Genet. Nov 1990;47(5):860-6. [Medline].

  22. Sander CA, Medeiros LJ, Weiss LM, et al. Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. Am J Surg Pathol. Dec 1992;16(12):1170-82. [Medline].

  23. Snyder MJ, Stenzel TT, Buckley PJ, et al. Posttransplant lymphoproliferative disorder following nonmyeloablative allogeneic stem cell transplantation. Am J Surg Pathol. Jun 2004;28(6):794-800. [Medline].

  24. Straus SE, Sneller M, Lenardo MJ, et al. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann Intern Med. Apr 6 1999;130(7):591-601. [Medline].

  25. Su HC, Lenardo MJ. Genetic defects of apoptosis and primary immunodeficiency. Immunol Allergy Clin North Am. May 2008;28(2):329-51, ix. [Medline].

  26. Uzel G. The range of defects associated with nuclear factor kappaB essential modulator. Curr Opin Allergy Clin Immunol. Dec 2005;5(6):513-8. [Medline].

  27. Vetrie D, Vorechovsky I, Sideras P, et al. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. Jan 21 1993;361(6409):226-33. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

lymphoproliferative disorders, LPD, immune dysfunction in children, immune deficiency disorders, immune disorder, X-linked immunodeficiency, agammaglobulinemia, autoimmune lymphoproliferative syndrome, severe combined immunodeficiency, common variable immunodeficiency

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Stuart S Winter, MD, Associate Professor, Department of Pediatrics, University of New Mexico Health Sciences Center
Stuart S Winter, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, New Mexico Pediatric Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Kathleen M Sakamoto, MD, PhD, Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA and California Nanosystems Institute and Molecular Biology Institute, UCLA
Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, International Society for Experimental Hematology, Society for Pediatric Research, and Western Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Timothy P Cripe, MD, PhD, Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.