Lymphomas

Question 1

CLASSIFICATION OF 2 MAIN TYPES OF LYMPHOMAS?

Answer 1

Classifications of NHL and HL: Clinically - 1. low, intermediate, high grade. 2. Acc. to ‘WHO’ - Tumors of B cells, T-cells, NK cells

1. NON-HODGKINS (NHL) –> presents at particular site but often dissemination.
   - Small lymphocytic lymphoma/chronic lymphocytic leukemia
   - Follicular lymphoma
   - Mantle cell lymphoma
   - Diffuse large B-cell lymphoma (DLBCL)
   - Burkitt’s lymphoma
   - Lymphoblastic lymphoma - childhood (40%) ,thymic origin (T-cells), rapidly progressing ->BM, associated with ALL, poor prognosis, uniform cells, high mitotic activity
   - Extranodal lymphomas
   - Adult T-cell lymphoma/leukemia??

2. HODGKINS (HL) --> present at single site with predictable spread to nearby LNs - depresses T-cell immunity.
5 sub-types: 
- Nodular sclerosis (60%)
- Mixed cellularity (30%)
- Lymphocytic predominance (5%)
- Lymphocytic rich (rare)
- Lymphocytic depletion (rare)

NB. common:
- Both arise in lymphoid tissue
- Monoclonal - all lymphoid neoplasms derived from a single transformed cell.
(B cell origination mainly (esp. those from germinal centers that have undergone somatic hypermutation))

Question 2

SMALL LYMPHOCYTIC LYMPHOMA (SLL) / (CHRONIC LYMPHOCYTIC LEUKEMIA - CLL)

Answer 2

• neoplastic proliferation of small mature naive B cells
• morpho, pheno and genotypically same as CLL except lymphocytosis >4000cells/mm3 in periph blood = CLL
• naive so cannot differentiate + suppresses non-tu functional B cells –> hypogammaglobinemia –> infections
• evetu. displaces normal marrow cells –> anemia, thrombocytopenia (bleeding), neutropenia etc.
• Bcl-2 over expression
• diffuse growth, mitotically active dividing cells form foci of proliferation centers.
  micro = small compact ly with dark round nuclei and clumpy chromatin. (May have fragile smudge cells in smear)
• older patients, asymptomatic, non-specific e.g. fatigue, anorexia
• lymphadenopathy, hepatosplenomegaly
• May be a precursor to more aggressive e.g. DLBCL

Question 3

FOLLICULAR LYMPHOMA (40%NHL)

Answer 3

• neoplastic prolif of CD20+ B cells in follicles forming a diffuse nodular appearance, enlarged germinal centers
• 2 types of cells present - centrocytes and centroblasts, proportions may differ at different stages.
• t(14;18) –> Bcl-2, no tingible body macrophages, nodular appearance - disturbs normal LN architecture –> helps distinguish from reactive follicular hyperplasia (e.g. infection)
  micro = small ly with angulated nuclei
• older people, painless lymphadenopathy, usu. involves BM
• possible progression to DLBCL (40%)
• symptomatic - low dose chemo & rituximab (anti-CD20Ab) (7-9yr survival)

Question 4

MANTLE CELL LYMPHOMA (4%)

Answer 4

• neopl prolif of CD20+ B-cells expanding/resembling mantle zone
• > 50yrs, men
• diffuse or nodular pattern
• tu cells larger w irreg nucleus
• involvement of BM, not do often peripheral blood
• also GIT - forms multifocal submucosal nodules resembling polyps
• fatigue, lymphadenopathy
• diagnosis - absence of proliferation centers (from SLL), t(11;14) –> cyclin D1
• aggressive, incurable (3-5yr survival)

Question 5

DIFFUSE LARGE B-CELL LYMPHOMA - DLBCL (50% of adult NHL, 15% in children)

Answer 5

• B-cell prolif (CD20+) - large cells (poorly differentiated), diffuse growth, aggressive (high grade)
  (can start due to e.g. chronic irritation to gut mucosa –>stomach lymphomas)
• may arise sporadically or transformation from a low grade lymphoma e.g. follicular, SLL
  (- may have30% mutations in BCL6 (regulator of germinal center B-cells), 30% t(14;18) –> BCL-2, remaining myc gene translocations etc.)
• associated with EBV (AIDS, immunosup), HHV-8 (Kaposi’s sarcoma)
  micro = large B-cells with round/irregular/cleaved nucleus and distinct vesicular nucleoli, macrophages w. apoptotic bodies found.
• rapidly enlarging mass at 1 or several sites
• enlarged LN and/or extra-nodal sites e.g. brain/GIT (any tissue/organ)
• aggressive, lethal and relapse is common after therapy
• BM involvem. rare –> poor prognosis, otherwise 50% remission (chemo)

Question 6

BURKITT’S LYMPHOMA (30% of childhood NHL)

Answer 6

• EBV associated, t(8;14) –> c-myc gene (cell growth)
• endemic in Africa –> jaw - mandible/maxilla, sporadic in US and other –> abdomen, bowel, ovaries etc.
  Micro = B cell lymphoma - uniform tu cells (intermediate size), round/oval nuclei, tissue macrophages - ingested nuclear debris –>starry sky (microscope), high mitotic activity.
• high grade tu, fast growing but can be cured. (chemo, immunoth - rituximab, transplant)etc.

Question 7

EXTRANODAL LYMPHOMAS

Answer 7

1. EXTRANODAL MARGINAL CELL LYMPHOMA
   - associated with chronic infl. e.g. Hashimoto’s, Sjorgen sy, H.pylori gastritis etc.
   - MALToma is an example in mucosal sites - gastric MALToma may decrease with H.pylori treatment.
2. Cutaneous T-cell lymphoma (mycosis fungoides) - neoplasia of T4 helper cells - skin rashes, infiltration of epidermis/dermis, older patients
3. Sezarys sy - - later stages of fungoides:
   - manifestation in skin, epidermotropism of CD4 Th cells
   - generalised erythroderma
   - Sezary/tu cells in blood (atypical T cells)
   - HSM

Question 8

CHARACTERISTICS AND DIFFERENCES BETWEEN NHL AND HL

Answer 8

1. NON-HODGKINS (NHL)
   - presents at particular site but often dissemination.
   - often involvement of multiple perip nodes (common involv of mesenteric nodes and Waldeyer ring)
   - common extra-nodal involvement
   - spread –> inv. many LNs
   - older usu. >40yrs

MICRO:
– monomorphic cells, an entire mass composed of mlg cells

2. HODGKINS (HL) – germinal center B-cell proliferation
   - present at single site with predictable spread to nearby LNs (step-wise) - depresses T-cell immunity. i.e. localized to a single axial group of nodes
   - no periph blood involv.
   - extra-nodal involvem uncommon
   - spread –> from neck (90%) to mediastinal, celiac LNs –> spleen, liver BM
   - younger < 30yrs

MICRO:

• • characteristic neoplastic (polymorphic) Reed-Sternberg giant cells (variants = popcorn/lacunar cells)
• • more reactive non-neopl inflam cells e.g. ly, macroph, plasma cells etc. and few RS mlg cells

Question 9

HODGKINS

Answer 9

• definitive diagnosis =
  1. RS cells – large cell . multi-lobed nuclei, prominent nucleoli, eosinophilic cytoplasm (usu. showing 2 nuceli/lobes w. clear nuclear memb+ large distinct nucleoli in each ‘owl-eye’ appearance)
• Hodgkin cells (practical)
  2. Lots of reactive inflam cells - ly, plasma cells, eosinophils etc.
• CD30 +ve
• 5 subtypes
• painless LN enlargement, occasionally B cell symptoms - fever, chills, night sweats
• distinguish NHL by biopsy
• response to treatment is good
• staging important for prognosis and therapy I-IV (LN involvement)
  I/II = less likely of systemic manifestations, those younger patients with more favorable sub-types, free of B symptoms
  III/IV - systemic, advanced B symptoms - fever, weight loss, anemia etc.