Lymphoma

Lymphoma - Margaret Wheless

Background

  • Malignancy of lymphoid cells comprising multiple different cancers of the immune system depending on the subtype and stage of development of cell/tissue involved
  • Characterized by lymphadenopathy & constitutional “B” symptoms:
    • Fevers, drenching night sweats and weight loss
  • Branch point of diagnosis:
    • Hodgkin: 10% - superficial, nodal disease with orderly spread
    • Non-Hodgkin: 90% - diffuse, nodal and extranodal disease with noncontiguous spread

 

Evaluation

  • B symptoms; pruritus (10-15% of pt with HL); history of radiation
  • Lymphadenopathy: painless, firm, fixed, >1cm
  • Exam: head & neck, tonsils, axilla, testes, liver, spleen
  • CBC, CMP, LDH, Uric Acid
  • HBV, HCV,  HIV, EBV, Quant gold, Treponemal Ab, ANA
  • Imaging: CXR most will eventually need PET-CT; MRI brain if neuro symptoms 
  • Diagnosis requires tissue
    • Excisional Lymph node biopsy (surg onc. Consult)
    • Core biopsy (CT guided procedure consult)
  • Ann Arbor Staging System: I. 1 LN region
    • II. >2 LN regions, same side of diaphragm
    • III. LN regions on both sides of diaphragm
    • IV. Dissem dz w/ 1+ extralymphatic organ

 

Non-Hodgkin Lymphoma (NHL)

Background

  • 65 y/o, M>F, 85-90% B-cell
  • Associated with immunodeficiency (HIV, post-transplant), autoimmune disease (both the disease and immunosuppression), infection (EBV, HTLV-1, H pylori,  HCV, Borrelia, C
  • psittacosis, Coxiella)
  • Stratify into:
    • Good prognosis: waxing/waning LAD, cytopenias, hepatomegaly or splenomegaly
    • Poor prognosis: Aggressive presentation: fever, night sweats, weight loss, TLS

 

Good Prognosis

Diagnosis

Key Features

Workup/Treatment

Follicular Lymphoma

 

20-30% of NHL

 

T (14; 18) bcl-2 over expression; CD19+, 20+, 10+, CD5-, CD23-

 

Grading based on # large cells

1: <25%, 2: 25-50%, 3. >50% (grade 3= closer to DLBCL)

Watchful waiting

Treatment:

  • bulky LAD
  • symptomatic disease
  • End-organ damage
  • Cytopenia’s

Excision or radiation (stage I)

Bendamustine-R (B-R) or RCHOP (> I)

Marginal Zone Lymphoma

Usually located in the GI, thyroid, orbit, lung, breast, salivary glands

 

Treatment:

  • Treat H pylori if MALT
  • Treat HCV if splenic

Extranodal MALT:

  • B-R, rituximab x 4 doses

Mycosis Fungoides

 

Sezary syndrome

 

Skin plaques with atypical CD4+ cells

 

May progress to Sezary syndrome aka T cell leukemia

Workup: Skin biopsy

 

Treatment:

Light therapy, topical steroids, superficial radiation

 

 

 

Aggressive/Poor Prognosis

 

Diagnosis

Key Features

Workup/Treatment

DLBCL

 

~25% of NHL; CD20+, CD45+

CD5+ confers the worst prognosis

Can arise as transformation from low-

grade lymphoma (Richter’s transformation)

 

60% present with advanced disease

Risk factors for CNS disease:  involvement of testicle, paranasal sinus,

epidural space, bone marrow or

>1 extra nodal sites + LDH

CNS disease needs IT and systemic MTX

 

If PET/CT reveals BM disease then no need for biopsy

 

Tx: RCHOP vs DA-R-EPOCH  (double hit)

 

Use IPI prognostic scoring

Mantle Cell  Lymphoma

7% NHL; CD20+, CD200+

T(11;14) =Cyclin D1

M>F; avg age ~50-60s

 

Most present with diffuse disease

Blastoid variant more often involves CNS

Dx: pathology from bx

Use MIPI prognostic tool

 

Treatment: Aggressive: R-hyperCVAD-M/ara-C

Poor PS: BR & Rituximab

Double or Triple Hit  Lymphoma

Similar to DLBCL with combination of bcl-2, bcl-6, or  myc aberrations conveying double or triple hits

 

Very aggressive needs intrathecal ppx even if no evidence of CNS disease

PET/CT for staging; if no evidence of BM involvement on PET, will need biopsy

Tx: Da-R-EPOCH vs R

hyperCVAD/MA vs R-CODOX-M/ IVAC

Burkitt Lymphoma 

MYC translocation - most commonly t (8;14) with path showing classic “starry-sky”

Rapidly growing tumors

HIV: CNS relapse is 30-50% if no CNS ppx

 

1. Endemic (African jaw); often EBV/CD21+ 

2. Sporadic (in the US): median age 30 at dx;  present w/ abdominal masses & metastasis

3. Immunodeficiency-related (often seen with CD4  counts >200); more often involve LN, CNS, and BM

R-EPOCH vs R-CODOX-M/IVAC 

Everyone gets CNS prophylaxis

 

TLS prophylaxis for all pts

 

Everyone will need TTE before anthracycline-based chemo

Lymphoblastic

Lymphoma

Express TdT+ (cyclin D1 -)

Aggressive; often present with mediastinal mass and CNS involvement

Consider empiric allopurinol before starting chemotherapy

Treated like acute leukemias

 

Will need LP with IT chemo

Anaplastic Large Cell  Lymphoma (ALCL)

< 2% of NHL

Primary cutaneous variant can arise from existing mycosis fungoides
Worse outcome predictor includes increased
β-2 microglobulin >3 

and age >40

Use IPI prognostic tool 

 

Treatment: check CD30 +/- status - CD30+: BV(brentuximab)+ 

CHP (cyclophosphamide, 

doxorubicin, prednisone)

CD30-: CHOP + etoposide

 

 

 

Hodgkin Lymphoma (HL)

Background

  • Bimodal Distritbution: 15-35 y/o and >50; M>F
  • CD15+, CD30+ (Reed Sternberg cells “owl eyes”)
  • Associated with EBV in immunocompromised pt
  • 4 classical types
    • Nodular sclerosing (60-80%): young adult, F>M, low stage, mediastinal LAD, collagen bands
    • Lymphocyte rich (5%): best prog
    • Lymphocyte depleted (<1%): worst prognosis, older, M>F, disseminated, HIV+, diffuse positive and RS cells
    • Mixed (15-30%): older, M>F, intermediate prognosis
  • 1 nonclassical (5%): nodular lymphocyte predominant, peripheral LN

 

Presentation

  • Lymphadenopathy (usually contiguous), generalized pruritus, Incidental mediastinal mass
  • B-Symptoms: fevers, night sweats, weight loss

 

Evaluation

  • IPS negative prognostic calculator: albumin <4, hemoglobin <10.5, male, stage IV by Ann Arbor, age>45, WBC count> 15K, lymphocyte <8%

 

Management

  • Stage I-II: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) ± RT
  • Stages III-IV: ABVD x6 or escalated BEACOPP (bleo, etop, doxo, cyclophos, vinc, procarbazine, prednisone)

Additional Information

  • Pts will need TTE prior to chemo given the use of anthracycline
  • Increased risk of secondary cancers (~25% of pt with 40% increased risk over next 40 years)