TOC

Oncology Lymphadenopathy & Lymphoma

E V A L U A T I O N O F L Y M P H A D E N O P A T H Y (AFP 2016;94:896)
• Generalized LAD: HIV, EBV/CMV/toxo, mycobacteria, SLE, meds (e.g. phenytoin), sarcoid, lymphoma, Castleman’s, Kikuchi dz, IgG4
• Localized LAD: cervical (EBV/CMV/toxo, mycobacteria, lymphoma), supraclav. (malignancy), axillary (infection, breast), inguinal (STI)
• Hx: exposures, travel, meds, B Sx (fever, drenching night sweats, >10% unintentional wt loss in 6mo), other s/sx of infxn/malignancy
• Exam: localization (think about area of nodal drainage), size (abnormal >1cm), consistency, fixation, tenderness (inflammation)
• Labs: CBC/diff, LDH, HIV (PCR if acute), HBV, HCV. Depending on pre-test probability: T-spot, RPR, ANA, EBV/CMV/toxo serologies
• Imaging: CT C/A/P w/ contrast, PET/CT can define node size, distribution, monitoring of response/progression (w/ Deauville scoring)
• Biopsy: consider if large (>2cm), persistent 4-6w, or increased size, w/ immunophenotyping & cytogenetics. Empiric steroids may
decrease yield of biopsy. Excisional (cells & nodal architecture) > core needle (tissue for molecular studies) > FNA (high false neg.)
LYMPHOMA GENERAL PRINCIPLES
Lymphoma Staging: if Hodgkin lymphoma (HL), add “B” if B Sx. PET Deauville score (1-5): 1 = no FDG uptake; 5 = markedly FDG-avid
Stage I: 1 LN region, or single extralymphatic organ Stage III: LN groups above and below diaphragm
Stage II: ≥2 LN groups on same side of diaphragm Stage IV: disseminated ≥1 extralymphatic organs
LN region: cervical (R/L), axillary (R/L), subpectoral (R/L), mediastinal, hilar (R/L), celiac, paraaortic, mesenteric, iliac (R/L), inguinal (R/L)
Workup: PET/CT, HBV/HCV/HIV serology, G6PD, quantitative bHCG (if applicable), PFTs (+DLCO), TTE (prior to anticipated chemo)
Fertility Preservation: semen, oocyte or ovarian tissue cryopreservation. Menstrual suppression: GnRH agonists if ↓platelet expected
H O D G K I N L Y M P H O M A (NCCN; 2023)
Bimodal age distribution (Lancet 2012;380:836). Reed-Sternberg cells (CD15+ CD30+ CD20- CD45- PAX5+ PD-L1+) in inflammatory milieu
S/Sx: neck LAD, mediastinal mass, pruritis, constitutional sx, ↑Eos. Rare: burning pain w/
alcohol, nephrotic syndrome (i.e. minimal change disease), liver dysfunction, skin lesions HL International Prognostic Score (IPS)
WHO classification: nodular sclerosis (70%), mixed cellularity (25%), lymphocyte rich 1 point/factor (JCO 2012;30:3383)
Age >45 Points 5y PFS
(5%), lymphocyte depleted (<1%). Nodular lymphocyte-predominant HL is distinct entity.
Male 0 88%
Treatment: note long-term risk of cardio- and pulm-toxicity, 2° malignancy (t-AML) Stage IV 1 84%
o Stage I-II: ABVD ± XRT. Stage III-IV: ABVD vs. BV-AVD (NEJM 2018;378:331) Albumin <4 2 80%
vs. BEACOPP ± XRT. Interim PET/CT helpful for escalating vs. de-escalating tx Hb <10.5 3 74%
o Relapsed/refractory: salvage chemo + auto-HCT; brentuximab vedotin (BV); WBC ≥15,000 4 67%
PD1 inhibition (pembrolizumab or nivolumab), bendamustine, allo-HCT Lymphocytes <600 <8% ≥5 62%

NON-HODGKIN LYMPHOMA
Most common blood cancer, a/w immunosupp., autoimmunity, infection (EBV, H. pylori, HCV, HIV, HHV8, HTLV1) (Lancet 2012;380:848)
Indolent (e.g. FL): incurable, but better prognosis vs. Aggressive (e.g. DLBCL): higher chance of cure, but worse prognosis overall
Diagnosis Prevalence Clinical Features Treatment
- Stage I-II: R-CHOP + RT; Stage III-IV: R-CHOP; if DHL, consider
Aggressive, rapid growth, nodal/extranodal
more aggressive Tx (i.e. R-EPOCH); if old/frail, R-mini-CHOP
Diffuse BCL2, BCL6, or MYC translocations common
- CNS ppx controversial; some give high CNS-IPI IT MTX
Large Prognosis: IPI, cell-of-origin (GCB > ABC)
~35% - Relapsed/refractory: CD19 CAR T-cells preferred (Lancet
B-cell Double-hit lymphoma (DHL): more
2022;399:2294, NEJM 2022;386:640) vs. salvage chemo + auto-HCT
(DLBCL) aggressive subtype w/ MYC + either BCL2 or
- Trials adding drugs to R-CHOP failed in most phase III RCT so far,
BCL6 translocations. Triple-hit = ultra-HR.
except polatuzumab (NEJM 2022;386:351)
Generally indolent; occasionally aggressive - Stage I/contiguous II: RT preferred; Stage II-IV: observation, anti-
Follicular
~25% t(14:18) BCL2+. High grade = more CD20 ± bendamustine (BR), lenalidomide (LR), CHOP, or CVP
(FL)
centroblasts. FLIPI score prognostic - Monitor for transformation (rapid LN growth, ↑LDH, B symptoms)
Often indolent, painless LAD, IgM M-protein - Only treat when “active” (Blood 2018;131:2745), i.e. cytopenia, bulky
Small or chronic No risk of leukostasis unless WBC >400k disease, progressive lymphocytosis w/ increase >50% over 2mo,
lymphocytic ~5% Prognosis: Rai/Binet, IGHV unmutated (HR), autoimmune dz (AIHA, ITP), significant constitutional symptoms
(SLL/CLL) ZAP70+ (HR), CD38+ (HR), FISH (del17p = - Evolving combinations with BTKi (zanubrutinib, acalabrutinib,
HR), genetics (TP53 mut. = HR) ibrutinib), anti-CD20 (obinituzumab, rituximab), and venetoclax
Wide clinical spectrum, can involve spleen, - Stage I/non-bulk II: BR, VR-CAP, R-CHOP, or LR + R maintenance
Mantle Cell
~5% GI, BM. Leukemic (SOX11-) often indolent - Stage II-IV: RDHA + platinum, R-CHOP, NORDIC or HyperCVAD +
(MCL)
t(11;14), cyclin D1+. MIPI score prognostic auto-HCT w/ R maint. Relapsed/refractory: BTKi, CD19 CAR T-cells
Extranodal MZL (MALT): a/w sites with - Gastric MALT: if H. Pylori+, quad Tx can cure; if H. Pylori-, RT
chronic inflammation, e.g. stomach w/ H. - Nongastric extranodal localized: RT, observation
Marginal Zone pylori+ t(11;18), salivary glands (Sjogren’s), - Advanced nodal: observe, rituximab + chlorambucil/bendamustine
~10%
(MZL) thyroid (Hashimoto’s), small intestine, etc. - Splenic MZL: if HCV+, HCV Tx can lead to regression. If HCV-,
Splenic MZL: often HCV+, cryoglobulinemia Rituxumab (preferred) or splenectomy (definitive for diagnosis to
Nodal MZL: generally indolent, similar to FL differentiate from splenic diffuse red pulp small B-cell lymphoma)
Burkitt Aggressive, extranodal sites (jaw if African). - More aggressive than DLBCL treatment: R-EPOCH, R-CODOX-
~1%
(BL) ↑spont. TLS. t(8:14), cMYC+, EBV/HIV M/IVAC, R-HyperCVAD. Relapsed: chemo + auto- or allo-HCT
Diverse varieties. Peripheral T-cell (PTCL) NOS most common. Cutaneous T-cell (CTCL) i.e. Mycosis fungoides,
T-cell lymphoma ~15% Sezary syndrome (disseminated). Anaplastic large cell (ALCL) a/w ALK, breast implants. Adult T-cell leukemia/
lymphoma (ATL) a/w HTLV-1, geography (e.g. Caribbean). Enteropathy-associated T-cell (EATL) a/w celiac disease
ABVD = Doxorubicin, Bleomycin, Vinblastine, Dacarbazine CVP = Cyclophosphamide, Vincristine, Prednisolone
BEACOPP = Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, DHA + platinum = Rituximab, Dex, Cytarabine and Carbo-, -Cis- or Oxali-platin
Procarbazine, Prednisone EPOCH = Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin
CHOP = Cyclophosphamide, Doxorubicin, Vincristine, Prednisone HyperCVAD = Hyper-fractionated Cyclophosphamide, Vincristine, Doxorubicin,
CODOX-M/IVAC = Cyclophosphamide, Vincristine, Doxorubicin, Methotrexate, Ifosfamide, Dexamethasone, alternated w/ methotrexate & cytarabine, followed by maintenance POMP
Etoposide, Cytarabine VR-CAP = Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone

Priyanka Pullarkat
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