Non-Hodgkin Lymphoma
Background
What is the pathologic definition of non-Hodgkin lymphoma (NHL)?
NHL is a monoclonal expansion of malignant B or T cells that lacks the pathologic characteristics of Hodgkin disease (HD) (no RS cells) and is typically characterized by nodal/focal involvement vs. the more disseminated presentation of leukemias.
How does the clinical presentation of NHL differ from that of HD?
NHL typically involves more nodes at presentation, is more likely to be extranodal, is more likely to spread in a noncontiguous fashion, and has a prognosis that is more strongly affected by histologic subtype than HD.
What are the most common presenting signs or Sx of NHL?
Painless adenopathy (axillary, inguinal, femoral) is the most common presenting sign of NHL. ~30% of pts have B Sx. Waxing and waning adenopathy suggests an indolent form of NHL. Tumor bulk may cause intestinal obstruction, urinary tract obstruction, or nerve compression.
What are B Sx?
B Sx include fever >38°C, >10% body weight loss in 6 mos, or drenching night sweats.
What is the NCI working formulation for NHL?
The working formulation groups NHL by clinical aggressiveness or grade with subgroups based on cell type or presentation.
Low-grade NHL: follicular (grades 1–2), chronic lymphocytic leukemia (CLL), MALT, mycosis fungoides
Intermediate-grade NHL: follicular (grade 3), mantle cell, diffuse large B-cell lymphoma (DLBCL), T/natural killer (NK) cell, peripheral T cell, anaplastic large cell
High-grade NHL: Burkitt, lymphoblastic
What is the WHO classification of NHL?
The WHO classification divides NHL into B- and T-cell/NK cell neoplasms. The indolent, aggressive, and highly aggressive subgroups roughly correlate to the aforementioned working formulation groups.
Is there a relationship between clinical aggressiveness and curability of NHL?
Advanced-stage indolent NHL is rarely curable. Intermediate-grade NHL may be curable even in advanced stages.
Without Tx, what is the life expectancy for pts with NHL of varying aggressiveness?
Pts with indolent NHL have survival measured in yrs. Pts with aggressive NHL have survival measured in mos, and those pts with highly aggressive Dz have an expected survival of wks.
What % of NHL is indolent, and what are the most prevalent subtypes?
~35% of NHL is indolent by the WHO classification. 95% of indolent NHL are follicular lymphoma (FL) (grades 1–2; 65%), small lymphocytic lymphoma (SLL) (18%), and marginal zone B-cell lymphoma or MALT lymphoma (12%).
What are common cytogenetic abnormalities associated with indolent NHL?
t(14;18) is seen in 90% of FLs. This results in overexpression of antiapoptotic Bcl-2. Chromosome 13 deletion, t(14;19), and trisomy 12 are associated with SLL and CLL. Trisomy 3 (60%) and t(11:18) (25%–40%) are associated with MALT lymphoma.
How is FL graded?
FL demonstrates a mix of centrocytes (small, cleaved cells) and centroblasts (large, noncleaved cells). Grade correlates to the density of centroblasts (e.g., 0–5 centroblasts/high-power field (hpf), grade 1; >15 −centroblasts/hpf, grade 3a).
What is SLL?
SLL is the same Dz entity as CLL but with a predominant manifestation in the spleen, liver, or nodes as opposed to peripheral blood or BM.
What is Richter syndrome? What is its rate of occurrence?
Richter syndrome is the transformation of SLL or CLL into DLBCL. It occurs in roughly 5% of cases.
How is bulky mediastinal Dz commonly defined?
Bulky mediastinal Dz is commonly defined as a mass greater than one third of the intrathoracic diameter at T5-6 on upright PA film.
How is bulky Dz defined outside of the mediastinum?
Outside of the mediastinum, bulky Dz is variably defined in clinical trials but most often is either any mass >5 cm or any mass >10 cm.
Workup/Staging
What are the pertinent focused aspects of the physical exam in a person with suspected NHL?
The physical exam should include complete nodal assessment including epitrochlear and popliteal groups. Cervical adenopathy palpable above the hyoid bone should prompt an ENT exam. (The Waldeyer ring is more frequently involved in NHL than in HD.) Exam of extranodal at-risk sites including the liver, spleen, testicles, bones, abdomen, and flanks is appropriate.
What lab studies should be performed?
Laboratory studies should include: CBC with differential, CMP, LDH, β2-microglobulin, serum protein electrophoresis, HIV, hepatitis B virus (essential as it may reactivate with rituximab Tx), and hepatitis C virus. BM Bx should be performed for all lymphomas. LP should be performed for CNS Sx, testicular or paranasal sinus involvement, or immunodeficiency.
What imaging studies should be performed?
The imaging workup should include CT C/A/P. PET is appropriate in most cases. MRI brain should be performed for CNS Sx, testicular or paranasal sinus involvement, or immunodeficiency.
How is NHL staged?
NHL is staged similar to HD using the Ann Arbor (AA) system:
Stage 1: involvement of 1 LN region or localized involvement of 1 extralymphatic organ or site (IE)
Stage 2: involvement of ≥2 LN regions on same side of diaphragm or localized involvement of 1 associated extralymphatic organ or site and its regional LN, with or without involvement of other LN regions on same side of diaphragm (IIE)
Stage 3: involvement of LN regions on both sides of diaphragm, which may also be accompanied by localized involvement of an associated extralymphatic organ or site (IIIE)
Stage 4: multifocal involvement of ≥1 extralymphatic organ, with or without associated LN involvement, or isolated extralymphatic organ involvement with distant nodal involvement
Note: Pts without B Sx are designated with an A, otherwise with a B. Pts with splenic involvement are designated with an S.
What is a major limitation to the AA staging of NHL (as opposed to HD)?
NHL typically spreads in a less contiguous fashion compared to HD and thus stage I NHL is very rare (10%).
How is NHL practically staged?
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