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Lymph Node Pathol ogy

Normal Lymph Node Clinical Presentation

Depend on anatomical distribution of disease
2/3rd of Non-Hodgkin’s Lymph oma (NH L) & Hodgkin’s Lymphoma (H L)
• Nontender Nodal Enlargement
o Localized
o Generalized
1/3rd are Extranodal
• Skin
• Stomach
• Brain
Multiple Myeloma (MM)
• Skeletal Bone Destruction (Pain, Pathological Fracture)
Lymphadenitis (In fection of Lymph Nodes ) Enlarging Mass(es), typically Painless, at site of Nodal/ Lymphoid tissue
Lymph Nodes u ndergo reactive changes Obstruction, Ulceration of Hollow organs – MALT – Pain
Acute/ Chronic Interference with Normal Organ Function – Solid Organ Infiltration
Chronic (Kidneys, Liver, Bone Marrow)
Follicular Hyperplasia
(Prominent Germinal Centers) Important Principles
Tissue Diagnosis is Mandatory
Traditionally All considered Malignant
(but wide range of clinical behaviours seen)
B cell in origin (80-85%)
Disrupt Normal regulatory mechanisms
(Lead to frequent Immune Abnormalities)
Monoclonal
(All derived from single transformed cell)
Neoplastic B & T cells – tend to Home & Grow in areas where their Normal
Counterparts resides
Disseminated at the time of diagnosis
HL spreads in orderly fashion
(Staging important for Treatment)

Classification
NHL (Working Formulation) HL
Cat-Scratch Disease
Low Grade Nodular Sclerosis
Skin Lesion (7-12 days after contact)
Intermediate Grade Mixed Cellularity
Enlargement of Regional Lymph Nodes
History of being Scratched by Cat High Grade Lymphocyte Depletion
Lymphocyte Rich /Predominance

Microscopic Features of Malignant Lymphomas

↓ Power ↑ Power
Loss of N ormal Architectural Loss of cellular Heterogeneity
organization
Presence of Absence of Aberrant Monotonous domination by Single
Cat-Scratch Disease
Follicle Formation cell type
Gram –ve
Pleomorphic
Cat-Scratch Disease Immune Cell Antigens detected by Monoclonal Antibodies
Extra-cellular Coccoba cillary
Microabscesses of varying sizes Primarily T cell associated Primarily Monocyte/ Macrophages
pathogen (Bartonella henselae)
(pink areas) CD3 CD13
CD4 CD33
Warthin-Starry Silver stain
Singly, Small Clumps, Chains Primarily B cell associated Primarily Stem cells
(in Necrotic Foci) CD10 CD34
2° Syphilis CD19
Florid Follicular Hyperplasia CD20
Partially Fused Lymphoid Follicles – assume Bizarre shapes Primarily NK cells On all Leukocytes
CD16 CD45 (LCA)
CD56

Most Common Lymphoid Neoplasms

↓ Grade Lymphoma cell types
Small lymphocytic
Small cleaved follicular

Toxoplasma Lymphadenitis
Painless Axillary Lymphadenopathy
Confirm by Serologic Tests
Hyperplastic Follicle with reactive germinal center (numerous Macrophages)
Clusters of Epitheloid cells (upper right of follicle)
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Non-H odgkin’s Lymphoma

Follicular Lymphoma (Low Grade Non-Hodgkin’s Lymphoma ) High Grade Lymphomas

Most common form among Caucasians (Not common in Malaysia) Burkitt Lymphoma
Middle age Categories
M=F (All Morphologically Identical)
Neoplastic cells closely resemble normal germinal centre B cells (Some Clinical, Genotype, Virological Difference)
Predominantly Nodular/ Nodular & Diffuse growth pattern within lymph node • African (Endemic)
Almost similar to Reactive Hyperplasia • Sporadic (Nonende mic)
Predominantly Small Cleaved cells • Aggressive type (HIV individuals)
Associated with Translocations of c-MYC gene on Ch8
IgH locus t(8;14) usually
Endemic tumours are latently infected with EBV
Endemic Sporadic
Children/ Young Adults Children/ Young Adults
Manifest at Extranodal sites Manifest at Extranodal sites
Mass over Mandible, Abdominal Abdominal Mass
Viscera (Kidneys, Ovaries, Adrenals) (Ileocaecu m, Peritoneum)
Very aggressive Very aggressive

Lymph node is effaced by Intermediate-sized Lymph oid cells

Intermediate Grade Lymphomas ↑ Mitotic Index
Large Cell Lymphomas ↑ Apoptotic cell death
Starry Sky pattern
(due to scattered benign Macrophages among malignant lymphoid cells)

Large Cell Cleaved Large Cell NonCleaved Burkitt Lymphoma

Starry Sky pattern
Diffuse Large B-cell Lymphoma
20% of all NHL
Constitute 60-70% of aggressive Lymphoid Neoplasms
Male slightly ↑

Immunoblastic, Plasmacytoid

Large cell size

Clinical (4-5x mature lymphocytes)
Rapidly enlarging mass Diffuse pattern of growth
(single nodal/ extranodal site) Some Morphologic Variation
(often symptomatic) Vesicular nuclei
(can arise at any site) Prominent 2-3 nuclei
Moderate abundant cytoplasm
Waldeyer ring, Oropharyngeal lymph node, Adenoids, Tonsils
Extranodal sites
Aggressive tumour & rapidly fatal if untreated
Very responsive to Chemotherapy Staging (Ann Arbor Staging System) – (Hodgkin’s & Non-Hodgkin’s)
• Complete Remission (60-80%)
• Complete Cure (50%)

Therapy
Limited stage Treated with Radiation Therapy
↓ Grade Lymphomas (can be curative)
Disseminated ↓ Grade No Therapy I II III IV
Lymphomas (90%) ↓ Morbidity Limited Chemotherapy Single Lymph 2 or More Lymph Involving Lymph Involvement
Bone Marrow Transplant Node area Nodal Areas nodes Above & outside Lymph
Aggressive Lymphomas Multiagents (≥ 5 drugs) Chemotherapy Involvement (con fined to 1 Below Node areas –
• Complete remission rate 60-80% side of Diaphragm Diffuse,
• 30-40% Cured diaphragm) Disseminated
disease of BM,
Liver, Extranodal
Prognosis 5-Year Disease Free Survival Rate (Hodgkin’s)
90% 75-90% 50-85% 40-65%
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Hodgkin’s Lymphoma (HL)

Definition Nodular Sclerosis

Characteristics Most common type of HL (70%)
Reed-Sternberg cells (Large, Abnormal cells) Women more common
Admixed with Non-Malignant Inflammatory Cells Mediastinal involvement present with stage II disease (80% cases)
Characteristic Feature
Lacunar (Reed -Sternberg variant)
Sclerosing bands of collagenous fibrosis forming a nodular pattern
Fibrosis Thickens the capsule & Divides proliferating processes into “nodules”
or islands
Numerous Lacunar variants (Classical Reed-Sternberg cells are infrequent)
Reed-Sternberg cells Most common type in Industrialized countries
Distinctive Tumour Giant cell Presents in Anterior Mediastinum & Neck (Young Adult Female)
Bi-Nucleated/ Bi-Lobed Lymph Node/ Thymu s divided into variably sized nodules
“owl-eyed nuclei” (by collagenous bands – sclerosis ) extending from a thickened capsule
Nodules composed of mix of
Lymphocytes
Eosinophils
Histiocytes
Classic Reed-Sternberg cells
Lacunar variant of Reed-Sternberg cells

Lymphocyte-Rich/ Predominant
Mononuclear “L&H” Hodgkin cells
Popcorn shape d nuclei
Inconspi cuous n uclei
Background of Small Lymphocytes (Lymphocyte predominant)
Classic Reed-Sternberg cells (rare & difficult to find)
May be Diffuse or Nodular
Limited disease in Neck of Young Patients
Reed-Sternberg cell Variants Associated with
Lacunar L&H (Lymphocytic & Histiocytic) cell (p opcorn cell) variant Reed-Sternberg cell
Popcorn/ L&H
Mononuclear Mixed Cellularity
Mummified Men (70%) with Late Stage (III-IV) Disease & B-symptoms
Systemic Manifestations (frequently)
Epidemiology Numerous Reed-Sternberg cells
Commonly Young Adults (but can present at any age) Mixed Inflammatory Background (obliterate normal architecture)
Incidence with respect to age bimodal Plasma cells (frequent)
1st peak – Late Adolescence, Young Adulthood Eosinophils (freq uent)
2nd peak – 6th Decade Fibrosis, Necrosis (small amount present)
Bimodal Curve shifts to Younger Ages in Undeveloped countries Mixture of Lymphocytes, Eosinop hils, Histiocytes, ↑ Reed-Sternberg cells
Male : Female = 2 : 1 ↑ Mononuclear variant of Reed-Sternberg cells

Clinical Lymphocyte-Depleted
Painless Lymphadenopathy in Superficial Lymph Nodes involving Associated with HIV Infection
Cervical nodes (60-70%) Clinical
Axillary nodes (10-15%) Abdominal organs
Inguinal nodes (6-12%) Retroperitoneal lymph nodes
Bone Marrow
Peripheral Lymph Node (involvement ↓ common)
Approximately 70% of patients present have
Advanced Stage
B symptoms (80%)
Characteristics
↑ Reed-Sternberg cells & Variants
Extensive Fibrosis
Small Lymphocytes (virtually absent)
Subtypes
Sarcomatous Diffuse Fibrosis
Unexplained Fever > 38°C ↑ Bizarre Reed-Sternberg cells Extensive Fibrosis
Night Sweats Bizarre Anaplastic Rare Reed-Sternberg cells
Loss of >10% Body Weight in 6 months Reed-Sternberg-like variants seen
Present in Retroperitoneum (without peripheral nodal disease)
Etiology Tissue contain Precollagenous Sclerosis, Pleomorphic Reed-Sternberg variants
Unknown
Possible Etiologic Factors Liver Involvement in Hodgkin’s Disease
Prior EBV Infection
Frequent BCL-2 Translocations
Epstein-Barr Virus (EBV)
Detected in approximately 40% of cases of classical HL
Clonal

WHO Classification/ Histological Type

Nodular Sclerosing (64% )(worst prognosis)
Lymphocyte-Ri ch/ Predomi nance (7%) (best prognosis)
Mixed Cellularity (25%)
Lymphocyte-Depleted (4%)
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Multiple Myeloma

Definition Clinical Course

Plasma cell Neoplasm Organ Infiltration
Men (common) Excess Ig
Involvement of Skeleton at Multiple sites Suppression of Humoral Immunity
Bone involvement predominates HyperCalcaemia
Lymph node Spread & Skin involvement Renal Failure
Prognosis – generally Poor
Presentation
Multifocal Destructive Bone Lesions Metastases
• Vertebral column (66%) Breast
• Ribs (44%) Lungs
• Skull (41%) Prostate
• Pelvis (28%) GIT
• Femur (24%)
• Clavicle (10%)
• Scapula (10%)
Punched -out lesion on Radiograph (1 -4cm in diameter)
Plasma cell neoplasm, Multiple Myeloma, related entities
Lymphoid neoplas m of terminally differentiated B cells
Expansion of single clone of Ig secreting plasma cells
Resulted in ↑ serum levels of a single homogenous Ig or its fragments

Hodgkin’s VS Non-H odgkin’s

Hodgkin’s Non-H odgkin’s
Usually Localised to Single lymph Not as Localised
node or Chain of node s
Orderly, Contiguous spread to Spread often Random &
Adjacent lymph nodes Unpredictable
↓ Peripheral Involvement ↑ Peripheral, Extranodal involvement
Morpholically distinctive No Reed-Sternberg cells
Reed-Sternberg (RS) cells

Multiple Myeloma
Multiple Lytic Lesions of Vertebrae

Generally Involves Contiguous Nodes Noncontiguous

Bone Marrow
Plasmacytosis > 30%
Malignant Plasma Cells
Rarely Extranodal Extranodal involvement Frequent
Bone Marrow involvement is unusual
(< 5%)
When involves the Spleen or Liver,
presents as Mass rather than Diffuse
involvement

Lab Results
Serum Electrophoresis

Peripheral Blood Film

Rouleaux Formation Rouleaux Formation

Urine
Bence-Jones Protein excreted by Kidneys (can cause Renal Impairment)