Diagnosing DLBCL

DLBCL diagnosis and patient characteristics

  • Patients are diagnosed based on a combination of characteristics, including clinical presentation, and laboratory, radiologic, and pathologic assessments8
    • The clinical presentation of DLBCL is variable4,9
    • Most patients present with peripheral lymphadenopathy or enlarged nodes in the mediastinum, the mesenteric region, or the retroperitoneum. As many as 40% of patients may present with extranodal involvement4,9,10
    • DLBCL is the most common lymphoma found in the central nervous system, the paranasal sinuses, Waldeyer's ring, the bone, the heart, the adrenals, the testes, the gastrointestinal tract, and the female genital tract11
    • Systemic B symptoms—fever, night sweats, and unexplained weight loss (>10% of body weight over the past 6 months)—occur in approximately 30% of patients4,9,10
  • Diagnosis of DLBCL should be made on the basis of excisional or incisional biopsy of a peripheral lymph node12
    • In specific circumstances where a lymph node is not easily accessible for excisional or incisional biopsy, a combination of core needle biopsy (CNB) and fine needle aspiration (FNA), in conjunction with other techniques (immunohistochemistry, flow cytometry, or cytogenetic analyses) used for making the differential diagnosis, may be sufficient for diagnosis of DLBCL. FNA or core needle biopsy alone is generally not suitable for the initial diagnosis of lymphoma
  • DLBCL often completely effaces the normal lymph node architecture, although partial nodal involvement can be seen. There are sheets of large atypical lymphoid cells and fine or broad bands of sclerosis that may be present in the background13
    • Diagnosis is made with immunophenotyping (Table 2).12 These assays should be used with other diagnostic tools
      • The 2 methods most frequently used to assess immunophenotype are immunohistochemistry (IHC) and flow cytometry9
    • Cytogenetic analysis by fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) testing can be used to determine the presence of cytogenetic events associated with DLBCL, such as chromosomal translocations t(14;18), t(3;v), t(8;14), or rearrangements of genes such as those encoding bcl-6 and IgH14

Table 2. Characterizing immunophenotypes in DLBCL12

Immunohistochemistry panel for DLBCL*

CD20 CD3 CD5 CD10 CD45 Bcl-2 Bcl-6 Ki-67 IRF-4/MUM-1 MYC

Flow cytometry panel for DLBCL

Kappa/lambda CD45 CD3 CD5 CD19 CD10 CD20

Additional IHC analysis to establish DLBCL subtype

Cyclin/D1 Kappa/lambda CD30 CD138 EBER-ISH ALK HHV8 SOX11

*Typical immunophenotype: CD20+, CD45+, CD3–; other markers used for subclassification.
Adequate immunophenotyping to establish diagnosis requires IHC with or without flow cytometry.
EBER-ISH=Epstein-Barr encoding region in situ hybridization; HHV8=human herpes virus 8.

  • Essential laboratory workup parameters include12:
    • Physical exam: attention to node-bearing areas, including Waldeyer's ring, and to size of liver and spleen
    • Performance status
    • B symptoms
    • Complete blood count (CBC), differential, platelets
    • Lactate dehydrogenase (LDH)
    • Comprehensive metabolic panel
    • Uric acid
    • PET-CT scan ± chest/abdominal/pelvic CT with contrast of diagnostic quality
    • Adequate bone marrow biopsy (>1.6 cm) ± aspirate; bone marrow may not be needed if PET scan is negative unless finding of another lymphoma subtype is important for treatment decision
    • Calculation of International Prognostic Index (IPI)
    • Hepatitis B testing
    • MUGA scan/echocardiogram if anthracycline or anthracenedione-based regime is indicated
    • Pregnancy testing in women of child-bearing age

Hepatitis B testing is indicated because of the risk of reactivation with immunotherapy + chemotherapy. Tests include hepatitis B surface antigen and core antibody for a patient with no risk factors. For patients with risk factors or previous history of hepatitis B, add e-antigen. If positive, check viral load and consult with gastroenterologist.