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.cancerimmune systemtumorchemotherapyradiotherapybone marrow transplantation

Lymphomas, multiple myeloma world map - Death - WHO2004 (per 100,000 inhabitants)

WHO Classification of Lymphoma non Hodgkin lymphoma

国外 NHL 分类 邵院 NHL 分类 non-Hodgkin ’ s lymphoma 国内外亚型分布比较

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.

Risk factors for the development of gastrointestinal lymphoma Crohn's disease Gastrointestinal nodular lymphoid hyperplasia Helicobacter pylori-associated chronic gastritis Celiac disease

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

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, 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 Approximately 20% of pts with NHL present with mediastinal adenopathy. In 3 to 8 % of pts with NHL, a superior vena caval syndrome is part of the clinical presentation. 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 10 ~ 35 % of pts with NHL will have primary extranodal lymphoma at initial dx, and about 50 % will have extranodal disease during the course. 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, and are uncommon in the indolent lymphomas. Other sites involved with aggressive non-Hodgkin's lymphomas at presentation include the testis, bone, and kidney. The skin should be carefully examined for lesions; all suspicious areas should be biopsied.

PHYSICAL EXAMINATION ： Extranodal sites Colonic involvement with lymphomaLymphoma affecting the kidney

Lymphoma of boneLymphoma 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 in 30 to 50 %, most commonly in the indolent histologies BM aspirates / BM biopsy It remains controversial whether patients require bilateral or unilateral bone marrow biopsies

DIAGNOSIS AND DIFFERENTIAL DIANGNOSIS

CLINICAL EVALUATION

Ann Arbor staging classification for Hodgkin's and NHL

"B" symptoms Fever — temperature >38ºC Weight loss —>10 percent over the past six months Sweats — the presence of drenching night sweats “B” symptoms are more common in aggressive/ highly aggressive histologies (47%). < 25 % with indolent lymphomas have B symptoms.

International Prognostic Index Age >60 Serum lactate dehydrogenase (LDH) concentration greater than normal 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, >50 percent 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 Low-intermediate risk High-intermediate risk to 5 High risk 26 44

Treatment

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

Blood, 11 June 2009, Vol. 113, No. 24, pp Differential efficacy of bortezomib plus chemo within subtypes of DLBCL

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