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Lymphoma, Follicular: Differential Diagnoses & Workup

Author: Cesar O Freytes, MD, FACP, Director of Bone Marrow Transplant Program, Professor, Department of Internal Medicine, Division of Hematology, University of Texas Health Science Center at San Antonio
Coauthor(s): Julianna A Burzynski, PharmD, BCOP, BCPS, Clinical Pharmacy Specialist in Hematology/Oncology, Mayo Clinic
Contributor Information and Disclosures

Updated: Nov 3, 2009

Differential Diagnoses

Chronic Lymphocytic Leukemia
Lymphoma, Diffuse Large Cell
Lymphoma, Diffuse Mixed
Lymphoma, Lymphoblastic
Mucosa-Associated Lymphoid Tissue

Other Problems to Be Considered

Autoimmune disorders
Chronic infections

Workup

Laboratory Studies

  • Complete blood count should be obtained, including examination of the peripheral blood smear.
  • Frequently, abnormal lymphocytes can be identified in the blood smear.
  • Blood chemistries, including LDH, uric acid, liver function tests, and creatinine, should be assessed.
  • LDH is an indicator of tumor load.
    • Elevated LDH is a negative prognostic factor.
    • Hyperuricemia can be observed upon presentation or during therapy.
    • Allopurinol should be considered in patients with hyperuricemia and before treatment to prevent uric acid nephropathy.
    • Increased creatinine can be observed in patients with renal obstruction caused by lymphadenopathy.
    • Increased alkaline phosphatase and bilirubin can be observed in patients with biliary obstruction due to lymphadenopathy.

Imaging Studies

  • Chest radiograph should be performed.
  • CT scan of chest should be considered if the findings from the chest radiograph are abnormal or cause suspicion.
  • CT scans of the abdomen and pelvis should be performed to determine if abdominal or pelvic adenopathy is present.
  • CT scans allow visualization of the kidneys, ureters, and the hepatobiliary system. At times, these organs are affected by obstruction due to lymphadenopathy or by parenchymal involvement with lymphoma.
  • Positron emission tomography (PET) scanning complements standard radiologic testing, but only a minority of patients will be diagnosed with a higher stage of disease.
  • PET scanning can distinguish between viable tumor and fibrosis in patients with residual lymphadenopathy after therapy, but because the majority of patients with follicular lymphoma are not curable, this finding will not change management. This is in contrast to Hodgkin lymphoma and intermediate-grade lymphoma where a positive PET scan might prompt salvage chemotherapy or radiation.

Procedures

  • Pathologic diagnosis from biopsy specimen
    • Biopsy is essential to establish a diagnosis of lymphoma. Obtain an excisional biopsy of an involved node.
    • A needle aspiration is not adequate for the initial diagnosis of lymphoma. If the disease is extranodal, a surgical biopsy sample should be obtained from the involved organ.
  • Bilateral posterior iliac crest bone marrow aspiration and biopsies
    • Although a diagnosis of follicular lymphoma can be established based on histologic findings from lymph nodes and involvement of the bone marrow can be diagnosed using morphologic criteria, cytogenetic analysis of bone marrow cells should be performed because the t(14;18) translocation is found in the majority of patients with follicular lymphoma and can help establish the diagnosis.
    • Immunophenotyping of bone marrow using flow cytometry also should also be performed. It can detect an abnormal clone of B cells, which also can help establish the diagnosis.
    • Polymerase chain reaction for bcl-2 in bone marrow also can help establish the diagnosis because the majority of follicular lymphomas are positive for bcl-2.

Histologic Findings

Follicular lymphomas exhibit a follicular or nodular pattern of growth reminiscent of germinal centers. This follicular pattern of growth contrasts with diffuse lymphomas, which usually are intermediate or high-grade neoplasms.

Several pathologic classification systems have been used since the late 1960s, including the Rappaport, Lukes-Collins, Kiel, Working Formulation, Revised European-American Classification of Lymphoid Neoplasms (REAL), and World Health Organization (WHO). Early classification systems relied solely on the architecture and cytologic appearance of lymph nodes. As more sophisticated tests became available, immunophenotypic, cytogenetic, and molecular criteria were incorporated in the diagnosis of lymphomas. REAL was based on the premise that a classification should attempt to define disease entities using all available information, including morphology characteristics and immunophenotypic, genetic, and clinical features.

More recently, the WHO classification of lymphoid neoplasms adopted the REAL classification and proposed several changes. The WHO classification changed the nomenclature from follicle center cell lymphoma to follicular lymphoma. The WHO classification calls for grading of the follicular lymphoma from grades 1-3 based on the number of centroblasts per high-power field (hpf) and recognizes the importance of reporting on the presence of diffuse areas. In addition, the WHO classification recognizes 2 variants of follicular lymphomas: cutaneous follicle center cell lymphoma and diffuse follicle center lymphoma. Follicular lymphoma according to the WHO classification is staged as grade 1 (0-5 centroblasts per hpf), grade 2 (6-15 centroblasts per hpf), and grade 3 (>15 centroblasts). Variants include cutaneous follicle center cell lymphoma and diffuse follicle center cell lymphoma.

Importantly, progression to diffuse large-cell lymphoma occurs in 10-50% of patients depending on the duration of disease presence. Transformation to diffuse large-cell lymphoma frequently is associated with rapid progression of the disease, including increasing adenopathy, development of systemic symptoms, and infiltration of extranodal sites. Progression to large-cell lymphoma is a poor prognostic factor, and most patients who experience transformation succumb to the disease.

Staging

Most patients with follicular lymphoma present at an advanced stage. Most patients have bone marrow involvement at diagnosis.

  • Stage I - One involved lymph node or lymph node area
  • Stage II - Two or more involved lymph nodes or lymph node areas on the same side of diaphragm
  • Stage III - Involved lymph node or lymph node areas on both sides of diaphragm
  • Stage IV - Disseminated disease such as bone marrow, liver, or central nervous system involvement

More on Lymphoma, Follicular

Overview: Lymphoma, Follicular
Differential Diagnoses & Workup: Lymphoma, Follicular
Treatment & Medication: Lymphoma, Follicular
Follow-up: Lymphoma, Follicular
Multimedia: Lymphoma, Follicular
References
Further Reading
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References

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Keywords

follicular lymphoma, non-Hodgkin's lymphoma, nodular lymphomas, low-grade lymphomas, indolent lymphomas, non-Hodgkin lymphoma, lymphoid tissue, lymph nodes, spleen, bone marrow, primary extranodal lymphoma

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Contributor Information and Disclosures

Author

Cesar O Freytes, MD, FACP, Director of Bone Marrow Transplant Program, Professor, Department of Internal Medicine, Division of Hematology, University of Texas Health Science Center at San Antonio
Cesar O Freytes, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, International Society for Experimental Hematology, and New York Academy of Sciences
Disclosure: Genzyme Grant/research funds Review panel membership; Otsuka Consulting fee Review panel membership

Coauthor(s)

Julianna A Burzynski, PharmD, BCOP, BCPS, Clinical Pharmacy Specialist in Hematology/Oncology, Mayo Clinic
Julianna A Burzynski, PharmD, BCOP, BCPS is a member of the following medical societies: American College of Clinical Pharmacy
Disclosure: Nothing to disclose.

Medical Editor

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.

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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