9. CHRONIC LYMPHOPROLIFERATIVE
DISORDERS(CLPDS) are a heterogeneous group of
malignancies characterised by the proliferation of mature
B and rarely T lymphoid cells in the peripheral blood,
bone marrow and/or lymph nodes/spleen and other
lymphoid tissues.
Classification-
1. FAB-MORPHOLOGY+
CYTOCHEMISTRY+IMMUNOHISTOCHEMIST
RY
2. WHO-
• Morphology
• Cytochemistry
17. B CELL CHRONIC LYMPHOCYTIC LEUKEMIA
Median age at diagnosis- 70 years
Incidence- Males= 2x Women
Symptoms related to- Anemia
Thrombocytopenia
Neutropenia
Neoplastic cells-
1. Small and mature appearing
2. Scant cytoplasm
3. Nuclei usually round
4. Chromatin regularly clumped(block-type chromatin)
5. Nucleoli inconspicuous
18. Diagnosis- Lymphocytosis >5 x 109 /L
Prolymphocytes <10%
Smudge cells
Cytogenetic abnormalities-
1. Trisomy 12
2. Del 11q22.3-23.1
3. Del 6q21-23
4. Deletions at 17p13.1(p53 aberrations)
5. 14q abnormalities and complex chromosomal
abnormalities
20. PROLYMPHOCYTIC LEUKEMIA
Aggressive leukemic disorder .
Often does not respond to treatment.
Incidence- 10% that of CLL.
Phenotypes-
1.Mature B cell
2.Mature T cell
21. B CELL PLL
70% cases of PLL.
Disease of adults
Male:Female-4:1
Lymphocytes-
1. Large cell
2. Moderate amount of pale basophilic cytoplasm
3. Moderately condensed chromatin
4. Single prominent nucleolus
23. T CELL PLL
Rare disorder of adults
Lymphocyte-
1. Medium size
2. Convoluted nuclear outlines
3. Prominent nucleolus
29. Bone marrow aspiration- DRY TAP
Bone marrow biopsy- monotonous infiltrate of abnormal
lymphocytes with small nuclei and abundant pale-staining
cytoplasm- FRIED EGG APPEARANCE
30. LARGE GRANULAR LYMPHOCYTIC LEUKEMIA
LYMPHOCYTOSIS-
1. Abundant pale staining cytoplasm
2. Azurophilic cytoplasmic granules
3. Nuclei with mature clumped chromatin
Phenotypes-
1. T LYMPHOCYTE TYPE
2. NK CELL TYPE
40. PARAMETER HODGKIN LYMPHOMA NON-HODGKIN
LYMPHOMA
STAGE Usually localized Usually widespread
DISTRIBUTION Usually central nodes Usually involves
peripheral nodes
MODE OF SPREAD Contiguous Non-contiguous
EXTRANODAL DISEASE Uncommon Common
PERIPHERAL BLOOD Never involved Can be involved
CELL TYPE Abnormal bizarre cells Resembles normal
lymphoid cells
TREATMENT REGIMEN Often ABVD Often CHOP
43. FOLLICULAR LYMPHOMA
Neoplasm composed of cell originating from the germinal
center.
Median age-50-60years
Presentation-generalized painless lymphadenopathy
peripheral blood involvement
bone marrow involvement
Lymph node-infiltrate of lymphoid cells forming poorly
circumscribed nodules
Neoplastic follicles diifer from reactive follicle in lacking
apoptosis of lymphocytes
Tingible body macrophages
Small cleaved cells(CENTROCYTES) and large
cells(CENTROBLASTS)
44. GRADING OF FOLLICULAR LYMPHOMA
GRADE DEFINITION
1 0-5 centroblasts per defined
HPF
2 6-15 centroblasts per defined
HPF
3 >15 centroblasts per defined
HPF
46. MANTLE CELL LYMPHOMA
Median age 60 years
Male predominance
Neoplastic cells-small to intermediate in size with round
to slightly irregular nuclear outlines.
Markers-
1. CD19+
2. CD5+
3. CD23-
4. FMC7+
5. sIg+(strong intensity)
6. Cyclin D1
48. MALT LYMPHOMA
Prsentation-localized extranodal disease
A preceding chronic inflammatory disorder(chronic
gastritis,sjogrens,hashimotos)
Neoplastic cells-
1. Small lymphocytes
2. Round to slightly cleaved nuclei
50. BURKITT LYMPHOMA
High grade Non-hodgkin lymphoma
High incidence in Africa(ENDEMIC SUBTYPE)
1/3rd of pediatric lymphomas outside
africa(SPORADIC SUBTYPE)
Extranodal involvement
Endemic-involves facial bones and jaw
Sporadic- intestine,ovaries or kidney
EBV associated
51. Biopsy- STARRY SKY APPEARANCE-
• The SKY represents the blue nuclei of the neoplastic
lymphocytes
• The STARS formed by scattered pale staining tingible body
macrophages.
Infiltrating lymphoid cells are intermediate in size with
nuclei approximately the same size as the nuclei of the
tingible body macrophages.
Multiple small nucleoli,mitotic figures and apoptotic bodies.
Markers-
1. CD19+
2. sIg+
3. CD10+
4. CD5-
54. HODGKINS LYMPHOMA-CLASSIFICATION
SUBTYPE SCLEROSIS LYMPHOCYT
ES
TUMOUR
CELLS
VARIANTS
VARIANTS CELL TYPE
LYMPHOCYTI
C
PREDOMINA
NCE
- ++++ + L AND H B-CELL
NODULAR
SCLEROSIS
PRESENT ++ ++ LACUNAR UNCERTAIN
CELL OF
ORIGIN
MIXED
CELLULARIT
Y
- ++ ++ - UNCERTAIN
CELL OF
ORIGIN
LYMPHOCYTI
C RICH
- ++++ + - UNCERTAIN
CELL OF
ORIGIN
58. ANN ARBOR STAGING OF HODGKIN’S
STAGE FEATURE
STAGE I Involvement of single lymph node region(I) or a single extra lymphatic
organ/site(IE)
STAGE
II
Involvement of two more lymph node regions on the same side of
diaphragm(II) or
Localized involvement of an extra lymphatic organ and one more more
lymph node regions on the same side of the diaphragm(IIE)
STAGE
III
Involvement of lymph node regions on both sides of diaphragm(III), which
may also be accompanied by localized involvement of an extra lymphatic
organ(IIIE) or involvement of the spleen(IIIS) or both(IIIES)
STAGE
IV
Diffuse or disseminated involvement of one or more extra lymphatic
organs or tissues with or without associated lymph node enlargement.
59. SUBCLASSIFICATION
A- without symptoms
B- Systemic symptoms:
1. Unexplained fever 38 degree Celsius.
2. Unexplained weight loss 10% body weight in
preceding 6 months.
3. Night sweats.
60. MALIGNANT LYMPHOMA KEY FEATURE
1. FOLLICULAR LYMPHOMA Nodular growth pattern
Lack of tangible body macrophages
CD19+,CD20+,CD5-,CD10+
Surface Ig strong intensity
t(14;18)
BCL-2 protein overexpression
BCL-2 gene rearrangement
2. MANTLE CELL LYMPHOMA Lack of large cells
CD19+,CD20+,CD5+,CD23-,FMC-7+
Surface Ig+ strong intensity
Cyclin-D1 overexpression
t(11;14)
BCL-1 rearrangement
3. MALT LYMPHOMA Accompanied by infectious or autoimmune disease
Often localized
Extranodal
Lymphoepithelial lesions
Benign follicles
Heterogeneous neoplastic infiltrate
Phenotype and genotype not specific
61. 4. WALDENSTROM MACROGLOBULINEMIA Lymphoid malignancy with plasmacytic differentiation
IgM
Hypervicosity syndrome
5. BURKITT LYMPHOMA Can be associated with EBV
Starry sky growth pattern
CD19+,CD20+,CD5-,CD10+
Strong surface Ig
t(8;14)
C-MYC gene rearrangement
6. ANAPLASTIC LARGE CELL LYMPHOMA Bizarre,anaplastic cells can resemble HD
T cell or Null phenotype
LCA+/-,CD30+,CD15-,EMA+/-,EBV-,ALK-1+/-
t(2;5)
7. CLASSIC HODGKIN LYMPHOMA Reed-Sternberg cells
LCA-,CD15+,CD30+,ALK-1-
Often EBV +
8. LYMPHOCYTIC PREDOMINANT HL Growth pattern frequently nodular
L and H cells
LCA+,CD20+,CD15-,CD30-,EBV-
63. KEY FEATURES OF PLASMA CELL DISORDERS
NEOPLASM FEATURES
1. MULTIPLE (PLASMA CELL) MYELOMA • LYTIC BONE LESIONS
• “M” SPIKE ON SERUM/URINE
ELECTROPHORESIS
• ROULEAUX ON BLOOD SMEAR
• >30% PLASMA CELLS IN BONE MARROW
2. PLAMACYTOMA • LOCALIZED MASS
• MONOCLONAL PLASMA CELLS
3. MONOCLONAL GAMMOPATHY OF
UNDETERMINED SIGNIFICANCE
• MONOCLONAL SERUM PROTEIN
• MONOCLONAL PROTEIN <3gm/dl
• LYTIC BONE LESIONS ABSENT
• BONE MARROW PLASMA CELLS <10%
64. CRITERIA FOR DIAGNOSIS OF MULTIPLE
MYELOMA(SALMON AND DURIE)
MAJOR CRITERIA-
1. Plasmacytoma on biopsy
2. Bone marrow plasmacytosis >30% plasma cells
3. M band in serum
• IgG >3.5 g/dl OR IgA >2 g/dl
• Light chain excretion in urine >/= 1 g/24 HOURS
MINOR CRITERIA-
1. Bone marrow plasmacytosis 10-30% plasma cells
2. Monoclonal globulin spike IgG <3.5 g/DL, or IgA <2g/DL
3. Lytic bone lesions
4. Normal IgM <50 mg/dl, IgA <0.1 g/dl OR IgG <0.6 g/dl
CRITERIA FOR MM
Diagnossi of myeloma is confirmed when at least-
• One major + one minor criteria OR
• 3 minor criteria, that must include 1 and 2 of minor criteria.
69. CELL SIZE DETERMINATION
Neoplastic cells are compared with the Reactive
Histiocytes interspersed among the lymphoma cells.
SMALL- Nuclei smaller than that of reactive histiocytes.
MEDIUM- Nuclei approx. same as that of histiocytes.
LARGE- Nuclei larger than those of histiocytes.
70. MEDIUM SIZED FOLLICLES-APPROACH
TO DIAGNOSIS
MAJOR DIFFERENTIAL DIAGNOSIS
1. Reactive follicular hyperplasia
2. Follicular lymphoma
3. Nodular mantle cell lymphoma
71. How to distinguish between reactive follicular hyperplasia and
follicular lymphoma?
FEATURE REACTIVE FOLLICULAR
HYPERPLASIA
FOLLICULAR
LYMPHOMA
FOLLICLES Discrete and separeated
by interfollicular lymphoid
tissue
A pattern of back to back
follicles with little
interfollicular tissue
TINGIBLE BODY
MACROPHAGES
Present Lack
CELLULAR POLARIZATION Into light and dark zones
present
Absent
POPULATION Heterogeneous population
of follicular cells
Predominance of
centrocytes in the
follicles
72. LARGE LYMPHOID NODULES:
APPROACH TO DIAGNOSIS
MAJOR DIFFERENTIAL DIAGNOSIS
1. NLPHL
2. N-LRCHL
3. NSHL
4. PTGC
74. DIFFUSE SMALL B-CELL LYMPHOMAS-APPROACH
TO CLASSIFICATION
MAJOR DIFFERENTIAL DIAGNOSIS
1. CLL/SLL
2. Lymphoplasmacytic lymphoma
3. Mantle cell lymphoma
4. Extranodal marginal cell lymphoma
75. LARGE CELL SCATTERED IN A BACKGROUND OF
SMALL LYMPHOCYTES
MAJOR DIFFERENTIAL DIAGNOSIS
1. Reactive lymphoid hyperplasia
2. T-cell/histiocytic rich large B-cell lymphoma
3. Hodgkin lymphoma
76. Possible diagnosis All large cells show
morphologic
features acceptable
for immunoblasts or
centroblasts(
nuclear size <x2.5
small lymphocyte
nucleus: nuclear
contour round to
oval)
Large cells are
atypical(with
irregular nuclear
folding or granular
chromatin),but
most nuclei are
<x2.5 small
lymphocyte nucleus
Most large cells
have nuclei >x3
small lymphocyte
nucleus
Reactive lymphoid
hyperplasia
+ - -
TCRBCL + + +
Hodgkin’s
lymphoma
- - +
77. CELL IDENTIFICATION BY
CCYTYOTCHOEMCICHAL EREMACTIIOSNTRY CELL TYPES
1. NON SPECIFIC ESTERASE • MYELOID CELLS
• MONOCYTES
• MEGAKARYOCYTES
• T LYMPHOCYTES(dot like staining)
2. CHLOROACETATE ESTERASE • MYELOID CELLS
• MAST CELLS
3. PEROXIDASE • MYELOID CELLS
• EOSINOPHILS
• MONOCYTES
4. SUDAN BLACK B • MYELOID CELLS
• MONOCYTES
5. METHYL GREEN PYRONINE • PLASMA CELLS
• IMMUNOBLASTS
6.PERIODIC ACID-SCHIFF WITH DIASTASE • PLASMA CELLS
7. TARTRATE-RESISTANT ACID PHOSPHATASE • HAIRY CELL LEUKEMIA
80. MOST USEFUL ANTIBODIES FOR ASSESSMENT OF LYMPHOID
PROLIFERATIONS
PROBLEM TO BE ASSESSED FIRST-LINE ANTIBODIES
B LINEAGE ? CD20( or CD79a, PAX5)
T LINEAGE ? CD3( OR CD2)
NK LINEAGE ? CD56, SURFACE CD3, CYTOPLASMIC CD3, TCR
FOLLICULAR CENTER CELL ? CD10( OR BCL6, HGAL)
FOLLICULAR LYMPHOMA OR HYPERPLASIA ? BCL2, CD10(interfollicular invasion)
CLL ? CD5, CD23
NORMAL MANTLE ZONE CELLS ? IgD
MANTLE CELL LYMPHOMA ? CYCLIN D1, CD5
BURKITT LYMPHOMA ? Ki67, CD10(+/-BCL6), BCL2, MYC
IMMATURE(PRECURSOR LYMPHOBLASTIC)CELL ? TdT
ANAPLASTIC LARGE CELL LYMPHOMA ? CD30, ALK
PLASMA CELL ? CD20- , CD138+
HISTIOCYTE ? CD163( or CD68)
INTERDIGITATIONG DENDRITIC OR
LANGERHANS CELL ?
S100( also LANGERIN/ CD207 for the latter cell type)
FOLLICULAR DENDRITIC CELL ? CD21 or CD35
HODGKIN LYMPHOMA ? CD30, CD15, PAX5
84. CHARACTERISTIC CYTOGENETIC FINDINGS IN
SPECIFIC LYMPHOMA TYPES
LYMPHOMA TYPE SPECIFIC CHROMOSOMAL
TRANSLOCATION
ONCOGENE OR TUMOUR
SUPPRESSOR GEENE
IMPLICATED
Follicular lymphoma t(14;18)(q32;q21) BCL2
Mantle cell lymphoma t(11;14)(q13;q32) CCND1
Extranodal marginal zone
lymphoma of MALT type
t(11;18)(q21;q21)
t(1;14)(p22;q32)
t(14;18)(q32;q21)
t(3;14)(p14.1;q32)
API2, MALT1
BCL10
MALT1
FOXP1
Burkitt lymphoma t(8;14)(q24;q32)
t(8;22)(q24;q11)
t(2;8)(p12;q24)
MYC
T-lymphoblastic
lymphoma/leukemia
t(1;14)
87. REACTIVE LYMPADENOPATHIES AND
THEIR DISTICTION FROM LYMPHOMA
INFECTIOUS MONONUCLEOSIS AND OTHER VIRAL
INFECTIONS
HYPERSENSITIVITY REACTIONS(PHENYTOIN)
KIKUCHI LYMPHADENITIS
88. REFERENCES
MCKENZIE-2ND EDITION,VOLUME 2
WHO CLASSIFICATION OF TUMOURS OF
HAEMATOPOIETIC AND LYMPHOID MALIGNANCIES-
4TH EDITION
WINTROBES-11TH EDITION
ROBBINS- 18TH EDITION
DIAGNOSTIC HISTOPATHOLOGY OF TUMOURS-FLETCHER
4TH EDITION,VOLUME 2
IOACHIM’S LYMPH NODE PATHOLOGY
INTERNET