Lymphoma

Lymphoma Origins (B-cell Pathway)

• Hair - memory

• Margin - margin

• mantle - mantle

• post germ → Post PG → HOD

• Naive → Calling (CLL) Naive

• Germ → germ in a flower (Follicular) → nokki Bark (Burkitt) cheyth

Hodgkin's Lymphoma (HL)

PATHOGENESIS

• Epstein-Barr Virus (EBV)
↓

• Latent membrane protein 1 (LMP-1) virulence factor
↓

• Increased activation of NF-κB growth signalling pathway
↓

• Post-germinal B cell proliferation
↓

• Hodgkin's lymphoma

Classical Hodgkin's Lymphoma:

Four Types:

• HOD went on a CAR () to Anthra () Win (Vincristine) some Blow ()

• Associated with EBV.

• Characterized by Reed-Sternberg (RS) cells (owl-eye).
• Large, bi-nucleated cells with prominent nucleoli.

• RS Cell Markers: CD15, CD30, PAX5.
• CD30: Most sensitive.
• PAX5: Most specific.

Clinical Presentation

• Average age group: Middle-aged - elderly.

• B symptoms:
• Fever: 
• For >10 days.
• Pel Ebstein type (waxing & waning pattern).
• Night sweats.
• Weight loss.

• Generalized/cervical lymphadenopathy.
• Painless
• Rubbery
• Most commonly affected lymph node: 
• Cervical lymph node.

• Hepatosplenomegaly in 30%

• SVC syndrome due to obstruction from mediastinal LN involvement
• Mediastinal involvement differential diagnosis (D/D):
• T ALL
• Nodular Sclerosis → Hodgkin Lymphoma
• Thymoma

• Paraneoplastic syndromes:
• Amyloidosis: 
• AA type.
• Pain with alcohol ingestion.
• Intense pruritis.

Nodular Sclerosis:

Non-Classical Hodgkin's Lymphoma (NLPHL):

• aka Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL).

• Has maximum B symptoms

• Not associated with EBV, CD15, CD30.

• Markers: CD20+, CD45+, EMA (epithelial membrane antigen)+, BCL6+.

• Shows popcorn RS cells (convoluted).

• Best prognosis overall.
• Nodular types often good prognosis
• Mnemonic: NLPHL (popcorn) = best.

• Mnemonic: 20 (CD20) vayassula Ima (EMA), 45 (CD45) vayassulla alde, backil (BCL2) adichu, for popcorn ()

MANAGEMENT

Treatment:

• ABVD regimen:
• A - Adriamycin (Doxorubicin).
• B - Bleomycin.
• V -Vinblastine.
• D - Dacarbazine.

Ann Arbor staging system:

Prognostic Factors: 

• Staging > tumour type.

Note: 

• Hairy cells exhibit markers: Annexin A+, CD 25+, CD 11c+, CD 103+.

Myeloproliferative disorders

• Group of disorders with increased production of:
• Red blood cells
• White blood cells
• Platelets

WHO Classification

• Chronic myeloid leukemia (CML)

• Polycythemia vera (PV)

• Primary myelofibrosis (PMF)

• Essential thrombocythemia

• Juvenile myelomonocytic leukemia (JMML)

• Chronic neutrophilic leukemia (CNL)

• Chronic eosinophilic leukemia

• Myeloproliferative neoplasm, not otherwise specified (MPN-NOS)

• Note - CLL not included

Non-Hodgkin's Lymphoma (NHL)

Two types:

1. B-NHL (7 types)

2. T-NHL (2 types).

Genetics Summary

Translocations

CD Markers Summary:

BNHLs (7 Types):

3. Burkitt's Lymphoma:

• Classical: African child, jaw swelling.

• Chr 8 + Even No. 
• 8;14, 8;22, 2;8
• Mnemonic: 8 looks like B → Chromosome 8
• NOTE: Translocation 8;21 → AML M2

• Associated with
• C myc,
• Ki 67 100%
• EBV.

• M/c NHL, M/c aggressive, M/c extranodal

• Cells: Cytoplasmic vacuolations, Oil Red O positive (fat).

• Biopsy: "Starry sky appearance" (white macrophages vs dark blue tumor).

• Mnemonic: Bar il poi → Pcket kaliyayi (vacuolation), Mike vach pattu padi (C myc), Jaw yil (Jaw swelling) Kiss (Ki67) cheyth (→ EBV) → Star nokki kidannu

7. Hairy Cell Leukemia:

• Common in: Boys.

• Mutation: BRAF mutation.

• Presentation
• Hypercellular Pancytopenia

• Markers: 
• Annexin A1+
• TRAP+ (red color) 
• DBA 44+ (new)

• Old Markers: 
• CD11, CD25, CD103 (CD103 important, side profile).

• Microscopy:
• Best on face contrast microscopy.

• Splenomegaly:
• Affects red pulp of spleen.

• Infections:
• Often MAC (Mycobacterium Avium Complex) due to pancytopenia.

• Bone Marrow:
• Aspirate = dry tap.
• Biopsy = "fried egg appearance".

• Mnemonic of Hairy Cell Leukemia:
• Boys (mc) have red hair (HCL) (TRAP+ → red color; Spleen red pulp)
• He is dumb (DBA 44) and Brat (BRAF)
• Only eat eggs (fried egg on BMB)
• Use MAC (Mycobacterium avium complex) to show off
• He brought a useless tap (dry tap) for 103 Rs (CD103) instead of buying for 11 (CD11) or 25 () Rs.
• Mnemonic: 103 → face turned to side (refer screenshot)
• So Trapped (TRAP) cheyth face (Face contrast) idich Red Pulp (Spleen red pulp) aaki

• Cladribine, Pentostatin
• ⛔ ADA
• NOTE: SCID
• ADA deficiency

• Lesch Neyhan syndrome
• ⛔ HGPRT

TNHLs (2 Types):

Anaplastic Large Cell Lymphoma (ALCL):

• CD30 positive.

• Shows 
• donut cells
• hallmark cells (kidney-shaped)

• Mnemonic:
• Anaplastic → ANayude Kidney eduth vaishna donut undakki 30 Rs nu vittu

Granuloma Shapes

NOTE: donut cells → Anaplastic Large Cell Lymphoma → CD30

Mycosis Fungoides (MF)

• Paul (Pautriers) tried sex (sesary) with
• mike (mycosis) → 45 yr old and
• dani (denileukin) → 4 yr old
• → Into brain (cerebriform nucleus)

• Description:
• Cutaneous T-cell lymphoma (CTCL) variant
• T-cell tumour in skin

• Cell Proliferation:
• CD4 positive &
• CD45 RO positive helper T-cells

• Course: Very indolent

• Metastasis: Very commonly seen

• Skin biopsy: 
• Pautrier's microabscesses (cancer cell clusters).

• Blood spread → Sézary Syndrome.
• Sézary cells with cerebriform nuclei (brain-like).

• DNA analysis
• Clonal arrangement of T cell receptor genes (TCR gene) → Standard now
• Mycoides → Fungal → Flower like
• Fungoides → T cell cancer ⇒ Clonal arrangement of TCR

Clinical Presentation:

• Location:
• Trunk (central girdle),
• upper lower limb
• Central body

• Stages:
• Patches,
• plaques,
• tumour/nodular,
• erythroderma

Sezary Syndrome:

Triad

1. Erythroderma

2. Peripheral lymphadenopathy

3. Sezary cells (>20% lymphocyte count OR >1000 cells/mm³)
• Atypical lymphocytes
• Grooved or cerebriform nucleus
• Seen in tissue & blood
• Mnemonic: Sezary cell → Sezary seed → middle groove (+)

• Cerebriform appearance
• Inverted papilloma → Thala (Cerebriform) thirinjavan

Histopathology:

• Epidermotropism:
• Many T-lymphocytes in epidermis

• Pautrier's microabscesses:
• Collections of T-cells forming microabscesses in epidermis
• Poultry → easily infected with fungus → fungoides

Treatment:

• Total Skin Electron Beam Therapy (treatment of choice)

Newer Drug:

• Denileukin Diftitox (IL2 fusion toxin)

• Mnemonic: Di → Di → 2

Multiple Myeloma (MM)

SKULL XRAY PATTERN APPROACH

 

• Definition: Cancer of plasma cells.

Normal Plasma Cell:

• Eccentric nucleus.

• Cartwheel chromatin.

• Perinuclear halo (Golgi for antibody synthesis).

• vs. Osteoblast:
• Also eccentric nucleus but paranuclear halo (shuttlecock appearance).

Diagnostic Criteria (CRAB & SLIM):

• Bone marrow plasma cells > 10%.

• Immunoglobulin (Ig) level > 3 g/dL (most common IgG).

Myeloma Defining Events:

• CRAB SLM
• C: Calcium elevated.
• R: Renal insufficiency.
• A: Anemia.
• B: Bony lytic lesions (X-ray: skull, vertebra; MRI: focus > 5mm).
• S: Sixty 60% plasma cells in bone marrow.
• L: Light chain ratio abnormality.
• M: MRI focal lesions > 5 mm.

• New IMWG biomarkers (≥60% cells, FLC ratio ≥100, MRI lesions)
• → diagnosis even without CRAB.

• MGUS
• Monoclonal gammopathy of Undetermined significance
• premalignant;

• Smoldering
• intermediate.

Peripheral Smear: 

• Plasma cells usually not seen.

• Rouleaux formation of RBCs.

Bone Marrow Aspirate Inclusions 
(all are immunoglobulins, mostly IgG):

• Mott cell/Mulberry cell

• Flame cells:
• Look "on fire"
• M/c with IgA increase.

Bone Marrow Biopsy: 

• Sheets of plasma cells 
  (eccentric nuclei).

Electrophoresis (Serum): 

• M-spike in gamma region
  (myeloma/monoclonal spike, → most commonly IgG, don't confuse with IgM).

Punched out lytic lesion/ rain drop lesion

• Well defined lytic lesions in the skull.

• Involves outer and inner tables equally.

• Seen in multiple myeloma & LCH

• It is a lytic lesion:
• No new bone formation.
• No increase in ALP.
• No hot spots on bone scan.

Plasma Cell Leukemia: 

• > 20% plasma cells in peripheral blood.

• Myleoma → > 20% plasma cells in bone marrow

• CD Markers for Plasma Cells:

Plasma Cell Type	CD45 (WBC marker)	CD19 (B cell marker)	CD38	CD138
Normal Plasma Cell	+	+	+	+
Malignant (MM)	-	-	+	+

Multiple myeloma → bad kid → do not show markers of Parents (WBC and B cell)