Transcript Approach to the diagnosis of non

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)
Figure 1.4: Percentage change in age-specific incidence of
NHL from 1975, persons, Great Britain
350
under25
25-44
45-64
65-74
75+
All
% of 1975 rate
300
250
200
150
100
1975
19761978
19811983
19861988
19911993
Period of diagnosis
19961998
20012003
NHL CANCER INCIDENCE 2002
Figure 1.5: Age-standardised incidence and mortality rates for NHL
in males by region of the w orld, 2002 estimates
Northern America
Australia/New Zealand
Western Europe
Northern Europe
Southern Europe
Eastern Africa
Western Asia
South America
Western Africa
South-Eastern Asia
Central America
Southern Africa
Incidence
Eastern Europe
Middle Africa
Northern Africa
Mortality
Eastern Asia
South Central Asia
0
5
10
15
Rate per 100,000 population
20
WHO Classification of Lymphoma
non 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
malignancy,
radiation therapy,
immunosuppressive agents,
chemotherapy,
organ transplantation， etc.
HIV-I,
HTLV-I,
Epstein-Barr virus (EBV),
hepatitis C virus,
Pyothorax-associated
lymphoma.
• Connective tissue diseases, immunodeficiency
disorders etc.
• Agricultural to pesticides and Agent Orange
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.
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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
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Waldeyer's ring
Standard lymph node sites
Liver and spleen
Abdominal nodal sites (mesenteric, retroperitoneal)
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
involvement is common in most histologic
subtypes of NHL.
• Diffuse hepatosplenomegaly is common in the
indolent lymphomas,
• Hepatic masses are more commonly seen in the
aggressive or highly aggressive lymphomas.
• Not all focal liver lesions in a patient with NHL
are due to lymphoma.
• Ascites may be present
PHYSICAL EXAMINATION： Abdomen and Pelvis
Retroperitoneal lymphadenopathy
Extranodal sites
• Patients with NHL will have primary
extranodal 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
PHYSICAL EXAMINATION：Extranodal sites
Lymphoma of bone
Lymphoma of testis
INITIAL LABORATORY STUDIES
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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
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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
0 to 1
2
3
4 to 5
Low risk
Low-intermediate risk
High-intermediate risk
High risk
5-yr OS
(%)
CR rate
(%)
73
51
43
26
87
67
55
44
Treatment
OS compared between
conventional chemotherapies and R-CHOP
100
CHOP
MACOP-B
ProMACE-CytaBOM
m-BACOD
Overall survival (%)
80
60
40
20
0
0
5
10
15
Patients over 60 (LNH98-5) 2002
侵袭性局灶NHL的治疗: 化疗或化疗+放疗
高危患者自体干细胞移植后生存优于化疗
LNH87-2 PROTOCOL
OS According to Gene-Expression Profiles in DLBCL
N Engl J Med, Vol. 346, No. 25.June 20, 2002
Genetic, molecular and characteristics
of the DLBCL subgroups and PMBL recognized by expression profiling
WHO classification of tumours and haematopoietic and lymphoid tissues,2008
Differential efficacy of bortezomib
plus chemo within subtypes of DLBCL
Blood, 11 June 2009, Vol. 113, No. 24, pp. 6069-6076
THANKS