LYMPHOMA

Huang Jinwen

Hematology Dept. of SRRSH

Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage of the disease.

Lymphomas, multiple myeloma world map - Death - WHO2004

(per 100,000 inhabitants)

100

150

200

250

300

350

1975 1976-1978

1981-1983

1986-1988

1991-1993

1996-1998

2001-2003

Period of diagnosis

% o

f 19

75 r

ate

under25 25-44 45-64 65-74 75+ All

Figure 1.4: Percentage change in age-specific incidence ofNHL from 1975, persons, Great Britain

NHL CANCER INCIDENCE 2002

0 5 10 15 20

South Central Asia

Eastern Asia

Northern Africa

Middle Africa

Eastern Europe

Southern Africa

Central America

South-Eastern Asia

Western Africa

South America

Western Asia

Eastern Africa

Southern Europe

Northern Europe

Western Europe

Australia/New Zealand

Northern America

Rate per 100,000 population

Incidence

Mortality

Figure 1.5: Age-standardised incidence and mortality rates for NHLin males by region of the world, 2002 estimates

WHO Classification of Lymphomanon Hodgkin lymphoma

What should we do ?

when we meet a patient with suspected non-Hodgkin’s lymphoma

PAST HISTORY • A personal or family history

• Relevant infectious illnesses

• Connective tissue diseases, immunodeficiency disorders etc.

• Agricultural to pesticides and Agent Orange

malignancy, radiation therapy, immunosuppressive agents, chemotherapy, organ transplantation ， etc.

HIV-I,

HTLV-I,

Epstein-Barr virus (EBV), hepatitis C virus,

Pyothorax-associated lymphoma.

CHIEF COMPLAINTS

Systemic complaints (B symptoms)

* Fever — temperature >38ºC

* Weight loss >10 percent over the past six months

* Sweats — the presence of drenching night sweats

Lymphadenopathy

* Rapid and progressive or Waxing and waning

* The duration, observed sites, and extent

* Peripheral lymphocytosis

Symptoms in gastrointestinal lymphoma according to involved site

Symptom Stomach n = 277 Small bowel n = 32 Ileocecal n = 26 Multiple sites n = 24

Pain 78 75 77 58

Loss of appetite 47 41 23 58

Weight loss 24 34 15 25

Bleeding 19 6 12 8

Vomiting 18 31 8 21

Night sweats 11 12 19 46

Diarrhea 4 12 19 29

Constipation 3 25 23 12

Fever 2 6 8 4

Perforation 2 9 - -

Ileus - 38 19 4

No symptoms 4 - - -

This table shows the percent of patients with the listed symptom at each of the four major

sites of disease. Data from Koch, P, et al. J Clin Oncol 2001; 19:3861.

ONCOLOGIC EMERGENCIES • Spinal cord compression• Pericardial tamponade• Hypercalcemia (adult T cell lymphoma)• Superior or inferior vena cava obstruction• Hyperleukocytosis (lymphoblastic lymphoma)• Acute airway obstruction (mediastinal lymphoma)• Lymphomatous meningitis and/or CNS mass• Hyperuricemia and tumor lysis syndrome• Hyperviscosity syndrome • Intestinal obstruction, intussusception• Ureteral obstruction, unilateral or bilateral• Severe hepatic dysfunction • Venous thromboembolic disease • Severe autoimmune hemolytic anemia and/or thrombocytopenia

PHYSICAL EXAMINATION

• Waldeyer's ring • Standard lymph node sites • Liver and spleen• Abdominal nodal sites (mesenteric, retroperitonea

l)• Less commonly involved nodal sites (eg, occipital,

preauricular, epitrochlear, popliteal)

PHYSICAL EXAMINATION ： Head and Neck

Waldeyer's ring

Head and neck

• Waldeyer's ring is more frequently observed in patients with NHL than in HL.

• A useful clue to the presence of involvement of Waldeyer's ring is enlargement of preauricular nodes.

• Primary central nervous system lymphoma commonly involves the eye.

• Lymphoma involving the orbital structures is rare, but may be seen in marginal zone and mantle cell lymphoma.

PHYSICAL EXAMINATION ： Superior vena cava syndrome

Chest and lungs

• ~ 20% of pts with NHL present with mediastinal adenopathy.

• A superior vena caval syndrome is part of the clinical presentation (3 to 8 %).

• Pleural disease is seen in about 10 percent of all patients with NHL at diagnosis.

• The differential diagnosis of mediastinal presentation includes infections,

sarcoidosis, Hodgkin's lymphoma, other neoplasms.

Mediastinal lymphoma

Abdomen and pelvis • Retroperitoneal, mesenteric, and pelvic involveme

nt is common in most histologic subtypes of NHL. • Diffuse hepatosplenomegaly is common in the ind

olent lymphomas, • Hepatic masses are more commonly seen in the ag

gressive or highly aggressive lymphomas.• Not all focal liver lesions in a patient with NHL ar

e due to lymphoma. • Ascites may be present

PHYSICAL EXAMINATION ： Abdomen and Pelvis

Retroperitoneal lymphadenopathy

Extranodal sites • Patients with NHL will have primary extrano

dal lymphoma at initial Diagnosis (10~35 %).

• The most common site of primary extranodal disease is the GI tract, followed by skin.

• Symptoms due to extralymphatic disease are usually associated with aggressive NHL.

• The skin should be carefully examined for lesions; all suspicious areas should be biopsied.

PHYSICAL EXAMINATION ： Extranodal sites

Colonic involvement with lymphoma Lymphoma affecting the kidney

Lymphoma of bone Lymphoma of testis

PHYSICAL EXAMINATION ： Extranodal sites

INITIAL LABORATORY STUDIES • CBC with differential• Renal and hepatic function• Serum calcium, electrolytes, and uric acid• Serum protein electrophoresis• the tumor markers beta-2 microglobulin

lactate dehydrogenase

etc

LYMPH NODE AND TISSUE BIOPSY

• Peripheral lymphonodes

• CT-guided core needle biopsies

• Bone marrow examination

• Laparoscopic multiple biopsies• Surgical operation

Lymph node selection

• Size:

* Significant enlargement

* Persistence for more than four to six weeks

• Site: * Supraclavicular nodes — 75 to 90 percent

* Cervical and axillary nodes — 60 to 70 percent

* Inguinal nodes — 30 to 40 percent

Studies on excised tissue

• An intact lymph node is critical for histologic, immunologic, molecular biologic assessment.

• The FNA findings of "lymphoma" requires to be confirmed.

• Immunologic, cytogenetic, and molecular studies are useful for making therapeutic decisions and assessing prognosis.

Reactive lymph node versus follicular lymphoma, and versus diffuse lymphoma

Bone marrow examination • BM involvement occurs commonly in the indolent

histologies. • BM aspirates / BM biopsy

CLINICAL EVALUATION

Ann Arbor staging classification for Hodgkin's and NHL

"B" symptoms

• “B” symptoms are more common in aggressive/ highly aggressive histologies (47%) .

• < 25 % with indolent lymphomas have B symptoms.

International Prognostic Index

• Age >60• Serum LDH• ECOG performance status 2 • Ann Arbor clinical stage III or IV • Number of involved extranodal disease sites >1

ECOG Performance Status

Performance Status Definition

0 Fully active; no performance restrictions

1 Strenuos physical activity restricted; fully ambulatory and able to carry out light work

2 Capable of all selfcare but unable to carry out any work activities, Up and about 50 percent of waking hours

3 Capable of only limited selfcare; confined to bed or chair, less than50% of waking hours

4 Completely disabled; cannot carry out any selfcare; totally confined to bed or chair

5-yr OS and CR rates according to IPI score

Score Risk group 5-yr OS CR rate

(%) (%)

0 to 1 Low risk 73 87

2 Low-intermediate risk 51 67

3 High-intermediate risk 43 55

4 to 5 High risk 26 44

Treatment

OS compared between conventional chemotherapies and R-CHOP

Patients over 60 (LNH98-5) 2002

100

80

60

40

20

0

0 5 10 15

CHOPMACOP-BProMACE-CytaBOMm-BACOD

Ove

rall

surv

ival

(%

)

侵袭性局灶 NHL 的治疗 : 化疗或化疗 + 放疗

LNH87-2 PROTOCOL

高危患者自体干细胞移植后生存优于化疗

N Engl J Med, Vol. 346, No. 25.June 20, 2002

OS According to Gene-Expression Profiles in DLBCL

Genetic, molecular and characteristics of the DLBCL subgroups and PMBL recognized by expression profiling

WHO classification of tumours and haematopoietic and lymphoid tissues,2008

Blood, 11 June 2009, Vol. 113, No. 24, pp. 6069-6076

Differential efficacy of bortezomib plus chemo within subtypes of DLBCL

THANKS