Lymphoma Flashcards
LYMPHOMA- overview
Solid tumors, lymphoid origin (LNs, bone marrow, thymus, tonsils, spleen, gut, liver, skin)
- Do not originate from BM (but may metastasize here)
- Do not start out in circulation (but may hematogenous-ly spread)
Hodgkins Lymphoma: 40%- Reed-Stenberg cells, most patients young adults, most present above diaphragm (75% mediastinal mass)- can have symptomology related to this
Non-Hodgkins Lymphoma: 60% - multiple types (lymphoblastic lymphoma, Burkitts- most common, diffuse large B cell, anaplastic large cell)- mostly in bone marrow <25% blasts, mediastinal masses rare
- *Presentation**
- Lymphadenopathy (large, increasing size, firm/rubbery/fixed, non-tender, supraclavicular)
- B-symptoms: fever, LOW, night sweats, body aches (33% in HL- prognostic significance, 10% NHL)
- Hepatosplenomegaly
Indications for investigation (LNBx): supraclavicular node, increasing size 2-4 weeks (or has not decreased 8-12wks), constitutional symptoms
Investigations
Lymph node biopsy (excisional) +/- splenectomy/BMA/liver Bx depending on site
Bloods
- FBE + film
- Immunoglobulins, B & T cell panels
- Viral serology
- HL: ESR
- NHL: CSF
Radiology
USS- abdo, mass
CXR- mediastinal mass
CT chest abdo pelvis
PET
MRI bones/spine, bone scan
+/- aspirates- peritoneal, pericardial, pleural
Staging
Murphy = NHL, Ann Arbor = HL
1. Tumor at one site
2. Two or more, unilateral (resectable primary)
3. Two or more bilateral (+ unresectable GI/mediastinal in NHL)
4. CNS or marrow involvement (NHL/Murphy)
4. Lung, liver or bone (HL/Ann Arbor)
NON HODGKINS LYMPHOMA- epidemiology & classification
Malignant solid tumor of undifferentiated lymphoid cells
- 60% of lymphoma, 15-35yrs
- Burkitt most common in 0-14yrs, DLBCL in teens
Characteristics
- Aggressive, diffuse and unpredictable spread, high growth and rapid doubling time
- Critical early diagnosis & early Rx
- Lymphoid tissues → BM, CNS
Risk factors
Immunodeficiencies (WAS, SCID), genetic syndromes (Bloom, AT), radiation exposure, post T cell deplete HSCT/organ transplant
Classification
- differentiated by cellular markers, some may have specific cytogenic features
- Immature
- Lymphoblastic lymphoma (LBL): 90% T cell origin, 10% B cell- <25% blasts in BM - Mature
- Burkitt lymphoma (BL): mostly B cell
- Diffuse large B cell lymphoma (DLBCL): multiple subtypes- mostly B cell
→ germinal centre B cell like (majority of paeds cases)- favorable prognosis
→ activated be cell like/primary mediastinal B cell type worse prognosis
- Anaplasic large cell lymphoma (ALCL) : mostly (70%) T cell, 20% no cell origin, 10% B cell
also determined by site of tumor
LBL = intrathorcic, sub-diaphragmatic, mets: BM & CNS
BL = abdominal, head & neck, mets: BM & CNS
DLBCL = abdominal & mediastinal, mets (rarely): BM & CNS
ALCL: systemic 90%, cutaneous 10%, mets: liver, spleen, lung, mediastinum
NON HODGKINS LYMPHOMA- clinical features & investigations
Clinical features
70% present with advanced stage- CNS/BM
B symptoms not prognostic
Capillary leak syndrome
Symptoms site specific
- Mediastinal- cough/dyspnoea, SVC obstuction
- Head & neck- lymphadenopathy, masses, nasal obstruction, CN palsies, vision loss
- CNS- headaches, vomiting, irritability, raised ICP, cord compression/paraplegia
- Bone pain
Tumor lysis syndrome common
Investigations
FBE, LFT, LDH
Bone marrow aspirate/biopsy → flow cytometry (immunophnotryping), cytogenetics/karyotype +/- FISH, microarray
LP/CSF cytospin
CT chest abdo pelvis
NON HODGKINS LYMPHOMA- Staging, treatment & prognosis, complications
Staging (Murphy)
Stage 1: Single area excluding mediastinum or abdomen
Stage 2: 2+ lymph node regions same side of diaphragm
Stage 3: 2+ regions above and below diaphragm- mediastinal, paraspinal, abdominal disease
Stage 4: Above with CNS/BM invasion
Treatment
- Prevent/treat complications- SVC obstruction/TLS
- Surgical excision
- Radiation therapy (emergency/rescue) if airway compromise, CNS disease
- Chemotherapy - low stage = CHOP +/- Rituximab, higher stages = aggressive CTx, reintroduce if relapse
MRD prognostic in ALCL & LBL (T cell)
If progressive/relapsed disease- consider repeat CTx +/- HSCT- allogenic superior (?graft vs tumor effect)
Localised disease 90-00% survival
Advanced 75-95% survival
Favorable prognosis: early stages, head & neck/peripheral or GIT nodes
Unfavorable prognosis: late stage, CNS/BM involvement, extra nodal disease, incomplete remission <2mo, relapse, delay in treatment, pleural effusion, high LDH >1000/uric acid >7.1 (indicates high tumor burden)
Complications
2nd malignancy: solid tumors, leukemia
Cardiac, thyroid & pulmonary disease
Infertility
HODGKINS LYMPHOMA
- *Hodgkin’s Lymphoma**
- Malignancy of B cells in germinal centres (lymph nodes, spleen, Peyer’s patches), also affects reticuloendothelial (phagocytes) /lymphatic systems
- 6% of chilhood cancers, 40% of lymphomas (most common teenage malignancy)
- Bimodal peak 15-35, then >50, M>F 3:1
Characteristics
- Reed-Sternberg cells on histopathology
- Slow spread to nearby LNs, less commonly haematogenous spread
- Highly sensitive to chemo + rad
Risk factors
- Environmental: higher in developed areas
- Host: immunologic disorders, infectious agents - EBV, CMV
Pathogenesis
- Reed-Sternberg cell- clonal cell, arise from germinal center, has lost gene expression/function of B cell
- Surrounded by inflammatory infiltrate (proportions of this determine subtype)
→ plasma cells, lymphocytes, eosinophils
→ activation of eosinophils & macrophages = increased IL11, IL6, TNF → B symptoms, decreased response to therapy & advanced stage
HODGKINS LYMPHOMA- types, clinical features and diagnosis
Types
Nodular sclerosing 40-60%- cervical/supraclavicular/mediastinl nodes
Mixed cellularity 1530% advanced disease, extranodal
Lymphocyte rich 5-15% localised
Lymphocyte depleted <5 widespread
Clinical features
90% painless lymphadenopathy
60% mediastinal masses (can have signs of SVC obstruction)- bulky = ⅓ of thoracic diameter/>10cm, usually anterior, risk with anaesthesia if >50% compression
30% B symptoms - used for staging
25% hepatosplenomegaly
Below diaphragm disease rare
If BM infiltration then signs of cytopenia
Diagnosis
CXR- establish presence of mass, size involved in prognostication
Excisional biopsy
BMA to f/o extensive disease
HODGKINS LYMPHOMA- staging, treatment, prognosis & complications
Staging
- Ct chest abdo pelvis, PET, FBE, ESR & ferritin
Ann Arbor
Consider asymptomatic/B symptoms, if extralymphatic extension vs localised, bulky disease, response to treatment
Stage 1: single LN, single extralymphatic site
Stage 2: 2 or more LNs same side of diaphragm, extralymphatic 1 or more same side diaphragm
Stage 3: Both sides o diaphragm, + extralymphatic organ/site
Stage 4: Disseminated disease
Treatment
Chemo + radiotherapy
- RT alone = prolonged remission, high cure rates however side effects (stunted growth, cardio/lung/thyroid toxicity)
- Multiagent chemotherapy
- ?NF-KB modulators
- Rituximab- anti CD20 (nodular sclerosing)
- Brentuximab= anti CD30
Prognosis
- >80% 5 year survival for all cases
- Favourable- young, female, lymphocyte rich, stage 1 non-bulky
- Unfavurable- lymphocyte depleted, advanced stage, bulky, male, poor CTx response, elevated inflammtory markers
Relapse most common in first 3 yrs after Dx up to 10- difficult to predict
- If relapse >1yr, asymptomatic - may able to Rx with CTx & RT 60-70% survival
- If relapse <1yrwith B symptoms or extranodal disease - Chemo, RTx +/- HSCT poor prognosis 40-50% survival
Complications
Secondary malignancies
Pulmonary, cardiac, spinal cord damage
Infertility
Hypothyroidism
NON-HODGKINS LYMPHOMA- large cell lymphoma
15-20% of NHL
Heterogenous
1. Diffuse large B cell lymphoma (DLBCL): B cell predominant mainly mediastinum and abdomen, rarely BM/CNS - more like HL
2. Anaplastic lymphoma- CD30/ALK fusion protein- mediastinum, skin, gonads, bone, multivalent CTx, CNS prophylaxis with IT CTx, +/- RT
3. Peripheral T cell lymphoma- skin, CND, LNs, lung, testes, GIT, muscles
NON-HODGKINS LYMPHOMA- Burkitt lymphoma
Mean age onset 11yrs
M:F 3>1
Rapidly growing, high risk TLS
Endemic: african, peak 7y/o, head & neck, spine, abdomen, gonad- breakpoints upstream of C-myc, predominantly CNS
Sporadic: peak worldwide, 11yrs, abdomen, BM, nasopharynx, mutations within C-myc , predominantly BM
Cytogenetics
90% t (8:14), c-myc gene chromosome 8,14q
also t(2,8). t (8,22) chromosome 2,22p
Treatment
Localised CTx 6 weeks -6mo - >90% survival
Advanced 4-6mo- 80-90% survival
PMBCL inferior outcomes
Rituximab
NON-HODGKINS LYMPHOMA- Lymphoblastic lymphoma
30-35% of NHL
Most are immature T cells (similar to T-ALL)
Only difference <25% on blasts
Most have anterior mediastinal mass
Respiratory distress in setting of SVC obstruction
Painless lump
CNS/BM rare
12-24mo CTx- intrathecal/intracranial if CNS spread
