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Lymph Node Pathol ogy

Normal Lymph Node

Lymphadenitis (In fection of Lymph Nodes )

Lymph Nodes u ndergo reactive changes
Acute/ Chronic
Chronic
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)
Low Grade
Intermediate Grade
High Grade

Cat-Scratch Disease
Skin Lesion (7-12 days after contact)
Enlargement of Regional Lymph Nodes
History of being Scratched by Cat

Cat-Scratch Disease
Microabscesses of varying sizes
(pink areas)

Clinical Presentation
Depend on anatomical distribution of disease
2/3rd of Non-Hodgkins Lymph oma (NH L) & Hodgkins 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)

Enlarging Mass(es), typically Painless, at site of Nodal/ Lymphoid tissue
Obstruction, Ulceration of Hollow organs MALT Pain
Interference with Normal Organ Function Solid Organ Infiltration
(Kidneys, Liver, Bone Marrow)

Cat-Scratch Disease
Gram ve
Pleomorphic
Extra-cellular Coccoba cillary
pathogen (Bartonella henselae)
Warthin-Starry Silver stain
Singly, Small Clumps, Chains
(in Necrotic Foci)

2 Syphilis
Florid Follicular Hyperplasia
Partially Fused Lymphoid Follicles assume Bizarre shapes

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
Follicle Formation
cell type
Immune Cell Antigens detected by Monoclonal Antibodies
Primarily T cell associated
Primarily Monocyte/ Macrophages
CD3
CD13
CD4
CD33
Primarily B cell associated
Primarily Stem cells
CD10
CD34
CD19
CD20
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)

HL
Nodular Sclerosis
Mixed Cellularity
Lymphocyte Depletion
Lymphocyte Rich /Predominance

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Non-H odgkins Lymphoma

Follicular Lymphoma (Low Grade Non-Hodgkins Lymphoma )
Most common form among Caucasians (Not common in Malaysia)
Middle age
M=F
Neoplastic cells closely resemble normal germinal centre B cells
Predominantly Nodular/ Nodular & Diffuse growth pattern within lymph node
Almost similar to Reactive Hyperplasia
Predominantly Small Cleaved cells

Lymph node is effaced by Intermediate-sized Lymph oid cells

Mitotic Index
Apoptotic cell death
Starry Sky pattern
(due to scattered benign Macrophages among malignant lymphoid cells)

Intermediate Grade Lymphomas

Large Cell Lymphomas

Large Cell Cleaved

High Grade Lymphomas

Burkitt Lymphoma
Categories
(All Morphologically Identical)
(Some Clinical, Genotype, Virological Difference)

African (Endemic)

Sporadic (Nonende mic)

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

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

Clinical
Rapidly enlarging mass
(single nodal/ extranodal site)
(often symptomatic)
(can arise at any site)
Waldeyer ring, Oropharyngeal lymph node, Adenoids, Tonsils
Extranodal sites
Aggressive tumour & rapidly fatal if untreated
Very responsive to Chemotherapy

Complete Remission (60-80%)

Complete Cure (50%)

Therapy
Limited stage
Grade Lymphomas
Disseminated Grade
Lymphomas (90%)
Aggressive Lymphomas

Treated with Radiation Therapy

(can be curative)
No Therapy
Morbidity Limited Chemotherapy
Bone Marrow Transplant
Multiagents ( 5 drugs) Chemotherapy

Complete remission rate 60-80%

30-40% Cured

Large cell size

(4-5x mature lymphocytes)
Diffuse pattern of growth
Some Morphologic Variation
Vesicular nuclei
Prominent 2-3 nuclei
Moderate abundant cytoplasm

Staging (Ann Arbor Staging System) (Hodgkins & Non-Hodgkins)

I
Single Lymph
Node area
Involvement

II
2 or More Lymph
Nodal Areas
(con fined to 1
side of
diaphragm)

III
Involving Lymph
nodes Above &
Below
Diaphragm

Prognosis 5-Year Disease Free Survival Rate (Hodgkins)

90%
75-90%
50-85%

IV
Involvement
outside Lymph
Node areas
Diffuse,
Disseminated
disease of BM,
Liver, Extranodal
40-65%

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Hodgkins Lymphoma (HL)

Definition
Characteristics
Reed-Sternberg cells (Large, Abnormal cells)
Admixed with Non-Malignant Inflammatory Cells

Reed-Sternberg cells
Distinctive Tumour Giant cell
Bi-Nucleated/ Bi-Lobed
owl-eyed nuclei

Reed-Sternberg cell Variants

Lacunar
Popcorn/ L&H
Mononuclear
Mummified
Epidemiology
Commonly Young Adults (but can present at any age)
Incidence with respect to age bimodal
1st peak Late Adolescence, Young Adulthood
2nd peak 6th Decade
Bimodal Curve shifts to Younger Ages in Undeveloped countries
Male : Female = 2 : 1
Clinical
Painless Lymphadenopathy in Superficial Lymph Nodes involving
Cervical nodes (60-70%)
Axillary nodes (10-15%)
Inguinal nodes (6-12%)

Unexplained Fever > 38C

Night Sweats
Loss of >10% Body Weight in 6 months
Etiology
Unknown
Possible Etiologic Factors
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%)

Nodular Sclerosis
Most common type of HL (70%)
Women more common
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)
Most common type in Industrialized countries
Presents in Anterior Mediastinum & Neck (Young Adult Female)
Lymph Node/ Thymu s divided into variably sized nodules
(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
Associated with
L&H (Lymphocytic & Histiocytic) cell (p opcorn cell) variant Reed-Sternberg cell
Mixed Cellularity
Men (70%) with Late Stage (III-IV) Disease & B-symptoms
Systemic Manifestations (frequently)
Numerous Reed-Sternberg cells
Mixed Inflammatory Background (obliterate normal architecture)
Plasma cells (frequent)
Eosinophils (freq uent)
Fibrosis, Necrosis (small amount present)
Mixture of Lymphocytes, Eosinop hils, Histiocytes, Reed-Sternberg cells
Mononuclear variant of Reed-Sternberg cells
Lymphocyte-Depleted
Associated with HIV Infection
Clinical
Abdominal organs
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
Bizarre Reed-Sternberg cells
Extensive Fibrosis
Bizarre Anaplastic
Rare Reed-Sternberg cells
Reed-Sternberg-like variants seen
Present in Retroperitoneum (without peripheral nodal disease)
Tissue contain Precollagenous Sclerosis, Pleomorphic Reed-Sternberg variants
Liver Involvement in Hodgkins Disease

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Multiple Myeloma
Definition
Plasma cell Neoplasm
Men (common)
Involvement of Skeleton at Multiple sites
Bone involvement predominates
Lymph node Spread & Skin involvement

Clinical Course
Organ Infiltration
Excess Ig
Suppression of Humoral Immunity
HyperCalcaemia
Renal Failure
Prognosis generally Poor

Presentation
Multifocal Destructive Bone Lesions

Vertebral column (66%)

Ribs (44%)

Skull (41%)

Pelvis (28%)

Femur (24%)

Clavicle (10%)

Scapula (10%)
Punched -out lesion on Radiograph (1 -4cm in diameter)

Metastases
Breast
Lungs
Prostate
GIT

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
Hodgkins VS Non-H odgkins
Hodgkins
Usually Localised to Single lymph
node or Chain of node s
Orderly, Contiguous spread to
Adjacent lymph nodes
Peripheral Involvement
Morpholically distinctive
Reed-Sternberg (RS) cells

Non-H odgkins
Not as Localised
Spread often Random &
Unpredictable
Peripheral, Extranodal involvement
No Reed-Sternberg cells

Multiple Myeloma
Multiple Lytic Lesions of Vertebrae

Bone Marrow
Plasmacytosis > 30%
Malignant Plasma Cells

Lab Results
Serum Electrophoresis

Peripheral Blood Film

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

Generally Involves Contiguous Nodes

Rarely Extranodal
Bone Marrow involvement is unusual
(< 5%)
When involves the Spleen or Liver,
presents as Mass rather than Diffuse
involvement

Noncontiguous
Extranodal involvement Frequent