NON HODGKIN LYMPHOMA Flashcards
INTRODUCTION
WHO classification of Lymphoid neoplasms classified Non Hodgkin Lymphoma into 4 out of the 5 broad categories
- Precursor B(pre-B)- cell neoplasms (immmature B cells)
- Peripheral B-cell neoplasms (mature B cells)
- Precursor T (pre-T)-cell neoplasms (immature T cells)
- Peripheral T-cell and NK-cell neoplasms(mature T cells and NK cells)
PRECURSOR B AND T CELL NEOPLASMS
Include just 2
1. Acute Lymphoblastic Leukemia (ALL)
2. Lymphoblastic lymphoma
1.) ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
-ALL is the most common cancer in children
-ALL is associated with infiltration of the CNS and sanctuary sites like the testes.
THE IMMUNOLOGIC CLASSIFICATION OF ALL:
A. B-CELL LINEAGE;
classification is based on presence or absence of cytoplasmic or surface markers viz:
-Surface immoglobulin (sIg) present: mature B-ALL — the leukemic form of Burkitt’s lymphoma)
-Cytoplasmic µ present : late pre-B-ALL
- Early pre B-ALL (most common, seen in children)
The rapid onset of symptom is due to MARROW INVOLVEMENT and PANCYTOPENIA.
B. T-CELL LINEAGE (T-ALL) (NOTCH1 mutation) is associated with mediastinal mass in young (adolescents) adult male
Factors causing good and Worse Prognosis in ALL
GOOD PROGNOSIS
1. Age between 2-10
2. A low white cell count
3. Hyperdiploidy
4. Trisomy of chromosomes 4, 7 and 10
WORSE PROGNOSIS
1. Age less than 2 years
2. Presentation in adolescence or adulthood
3. Peripheral blood blasts > 100,000
2.) LYMPHOBLASTIC LYMPHOMA
The majority of cases are T cells and are aggressive and rapidly progressive.
Clinical: young males with mediastinal mass
The leukemic phase of lymphoblastic lymphoma is similar to T-ALL.
PERIPHERAL B-CELL NEOPLASMS
9 in number (CFHDBMMML)
1.Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)
2. Follicular lymphomas
3. Hairy cell leukemia
4. Diffuse large B-cell lymphoma
5. Burkitt lymphoma
6. Mantle Cell Lymphoma (MCL)
7. MALToma
8. Multiple myeloma
9. Lymphoplasmacytic lymphoma
CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LYMPHOMA
CLL is very similar SLL aka well differentiated lymphocytic lymphoma
Presentation with blood findings = CLL
(Absolute lymphocyte count > 5000)
Presentation with lymph node findings = SLL
SLL is a proliferation of small B-lymphocytes which have B-cell markers and one T-cell marker(CD5), like B-CLL
CLL includes
B-CLL (95% of cases) CD19 & 20
T-CLL (5% of cases) CD5
CLL CLINICAL CHARACTERISTICS AND FEATURES
1-The most common and most indolent of all leukemias
2-Mean age at time of diagnosis is 60 years.
3-The malignant cells are nonfunctional thus patients develop hypogammaglobulinemia==increased risk of infection.
4-CLL is associated with warm autoimmune hemolytic anemia (AIHA) (10% of cases), which will cause spherocytes to be observed
1.Patients are often asymptomatic at diagnosis.
2.When symptoms appear, they are nonspecific and include easy fatigability, weight loss, and anorexia.
3.Generalized lymphadenopathy and hepatosplenomegaly are present in 50% to 60% of symptomatic patients.
TREATMENT:
1.“Gentle” chemotherapy and immunotherapy(anti-CD20) in symptomatic patients.
2.Hematopoietic stem cell transplantation to young pt.
3.BTK inhibitors.
FOLLICULAR LYMPHOMA
-The most common form of indolent NHL
-All are derived from B-Lymphocytes
CLINICAL FEATURES
1-commonly present with disseminated disease (more advanced stage)
2-generalized lymphadenopathy (extranodal involvement is uncommon).
3-has a better prognosis than diffuse lymphomas (median age of survival is 7 to 9 years).
4-doesn’t respond to therapy (palliative tx with low-dose chemotherapy or immunotherapy)
5-up to half of cases will progress to a diffuse large-cell NHL
DIFFUSE LARGE B CELL LYMPHOMA
COMMON FEATURES
1-Dysregulation of BCL6.
2-Composed of large cells with diffuse growth pattern.
3-May present at extranodal sites: CNS, stomach, etc.
4-Aggressive, rapidly proliferating tumour
5-Median age is about 60 years
6-May respond to therapy.(60% to *80% complete remission, 40% to 50% cure with chemotherapy)
BURKITT LYMPHOMA (SMALL NON CLEAVED LYMPHOMA)
3 categories
1. African (endemic) Burkitt lymphoma:
-Involvement of mandible or maxilla is characteristic.
-may involve abdominal viscera: kidneys, ovaries and adrenal glands.
-mainly in children or young adults.
-All are associated with latent infection with EBV
- Sporadic (nonendemic) Burkitt lymphoma:
-Commonly involves the abdomen (ileiocecum and peritoneum)
-15 % to 20% are associated with EBV - Aggressive lymphoma occurring individuals infected with HIV (HIV-associated Burkitt lymphoma)
-25% is associated with EBV
MICROSCOPY:
i. Medium-sized lymphocytes with a high mitotic rate.
ii. “Starry-sky” appearance is due to numerous reactive tangible-body macrophages (phagocytosis of apoptotic tumour cells).
TRANSLOCATIONS OR CHROMOSOMAL ABNORMALITIES OR GENE DEFECTS OF THE LYMPHOID NEOPLASMS AFOREMENTIONED
1.Burkitt lymphoma— Translocation of MYC gene on chromosome 8, usually t(8;14)
2.DIffuse large b-cell lymphoma — Dysregulagion of BCL6
3.Follicular lymphoma — characteristic translocation is t(14;18)
4. ALL — t(12;21)
5. CLL/SLL — t(2;14)
PLASMA CELL NEOPLASMS
Plasma cell neoplasms/dyscracias are B-cell proliferations that contain neoplastic plasma cells that secrete a monoclonal Ig or Ig fragment (tumour markers)
They include:
1. Multiple myeloma (plasma cell myeloma).*
2. Waldenström macroglobulinemia
3. Heavy-chain disease
4. Primary or immunocyte-associated amyloidosis
5. Monoclonal gammopathy of undetermined significance (MGUS).*
MULTIPLE MYELOMA
—MM is the most common primary tumor arising in bone of adults, commonly associated with hyperCalcemia, Renal failure, Acquired immune abnormalities and lytic Bone lesions (CRAB).
LAB:
-Increased serum protein with normal serum albumin
-M-spike (monoclonal immunoglobulin spike): most common is IgG (60%), next is IgA (20%).
-20% express Bence-Jones proteins, which are light chains that are small and can be filtered in urine.
Histology:
-bone marrow has increased number of plasma cells (>20% is characteristic)
-peripheral blood may show rouleaux
—Multiple lytic bone lesions due to osteoclastic activation factor (OAF)
—Lytic bone lesions cause hypercalcemia, bone pain, and increased risk of fracture.

Complications:
-Increased risk of infection
-Renal disease, such as myeloma nephrosis
-Amyloidosis (10%) due to amyloid light (AL) chains
- Increased IL-6 is associated with a poorer prognosis(myeloma cells survival depends on IL-6)
PLASMACYTOMA
Plasmacytoma are aggregates of atypical plasma cells, which may be located:
—Within the bone: precursor lesions to later develop into myeloma.
—Outside the bone (extramedullary): usually found within the upper respiratory tract and are not precursor lesion for myeloma.
MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE (MGUS)
—M protein is found in 1-3% of asymptomatic individuals over the age of 50 (the incidence increases with increasing age).
—About 20% of these individuals will develop a symptomatic plasma cell dyscrasia (esp. MM) in 10-15 years.
PERIPHERAL T-CELL AND NATURAL KILLER CELL NEOPLASMS
6 in NUMBER
PAAMEL
1. Peripheral T-cell lymphoma(“waterbasket” diagnostic category).
2. Anaplastic large cell lymphoma.*
3. Adult T-cell leukemia/lymphoma (ATLL).*
4. Mycosis fungoides (MF) and Sézary syndrome (SS).
5. Extranodal NK/T-cell lymphoma
6. Large granular lymphocytic leukemia.
PERIPHERAL T-CELL LYMPHOMAS, UNSPECIFIED
—These lymphoma cells are largely a “wastebasket” category for tumors that do not fit any other WHO criteria.
—No morphologic feature is pathognomonic, but certain findings are characteristic:
Tumor cells diffusely efface lymph nodes —and are commonly composed of a pleomorphic mixture of variably sized malignant T cells.
+By definition, these all have a mature T-cell phenotype; they express pan T-cell markers (e.g., CD2, CD3, CD5) and have clonal T-cell receptor rearrangements
ANAPLASTIC LARGE-CELL LYMPHOMA
Anaplastic large-cell lymphoma is an entity defined by chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene on chromosome 2p23.
