Pathology of Hematopoietic System

2012-2013
By Dr.Mai Ali
" Diseases of Lymphoid Tissue "
The Lymphoid System: The system which is responsible for the
complex cellular and molecular interactions that makes up the
immune response.
It includes:
A) Central lymphoid tissue: includes the thymus and bone
marrow.
B) Peripheral lymphoid tissue: includes the remaining lymphoid
organs. (lymph nodes, spleen, tonsils, etc)

Diseases of lymphatic vessels

1 - Acute lymphangitis: acute inflammation of
lymphatic vessels and the peritymphatic blood
vessels. It is due to streptococcus pyogenes
infection
Complications: Chronic lymphangitis
2- Erysipelas: Spreading acute lymphangitis of
dermis usually of the face due streptococcus
pyogenes infection
Pathology: a- The area is raised, painful, red
with well defined margin and endurated; and
Spreads rapidly
b- Cervical lymphadenitis
Course: Disease lasts 1-3 weeks and heals with
no disfigurement
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3- Chronic lymphangitis:
o Non specific:-Following acute lymphangitis
o Specific:- T.B, $, Filariasis.
4- tumours
Benign:
- Capillary lymphangioma
- Cavernous lymphangioma
Malignant
- Lymphangiosarcoma
Diseases of lymph nodes
I) Acute lymphadenitis
a- Bacterial: Acute inflammation of
regional lymph nodes draining an acute
bacterial infection (usually pyogenic
mainly face and hand)
N/E: The Lymph nodes are discrete
enlarged and soft.
- The cut surface bulges out and is
pink grey.
M/E: L.N show large germinal centers
containing numerous mitotic figures,
sometimes a neutrophilic infiltrate &
necrosis resulting in the formation of
an abscess.
Clinically: They are discrete, enlarged,
soft, painful and tender.
Complications:
Acute suppurative lymphadenitis
Chronic non specific lymphadenitis
b- Viral: Due to glandular fever
II)

Chronic lymphadenitis
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1- Chronic non specific lymphadenitis: Occurs in lymph nodes

draining foci of chronic non specific inflammation.
N/E: Affected nodes are matted, moderately enlarged and firm.
Cut surface has a red tinge and is hemogenous.
Reaction heals by fibrosis.
2- Chronic specific (granulomatous) lymphadenitis as infective
granulomas
Causes of lymph node enlargement
I- Acute lymphadenitis
II- Chronic lymphadenitis
III) Hyperplastic lymphadenopathy
Follicular hyperplasia
Sinus histiocytosis.
Nodes draining tumour
IV)

Histocytosis X: Due to proliferation

of langerhans cells.
V) Lymphomas: either
Hodgkins lymphoma
Non Hodgkins lymphoma
VI) Seconderies: either from
Carcinomatous
Sarcomatous
Lymphomas
Definition: Malignant neoplasms derived from cells native to
lymphpid
tissues
(lymphocytes
and
rarely
histiocytes).
According to the presence or absence of of characteristic ReedSternberg (RS) cell or their variants;
Two broad categories are recognized:
Hodgkins lymphoma
Non Hodgkins lymphoma
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Hodgkins lymphoma (HL)

A group of neoplasms the diagnosis of which are rests on the
identification of Reed-Sternberg (RS) cell or their variants in the
appropriate background of reactive inflammatory cells.
That arises in a single lymph node or chain of lymph nodes.
NB: Carl Sternberg (1898)9 and Dorothy Reed (1902)10 are
credited with the first definitive and thorough descriptions of
Hodgkin lymphoma
Clinical characters
The disease has two peaks; 1st in young adults; 2nd peak over
the age of 50.
Localized to single axial group of L.N (cervical, mediastinal,
para- aortic L.N) then spread in a stepwise fashion to the
contiguous nodes.
Mesentric nodes & Waldeyer ring rarely involved.
Extra- nodal involvement is uncommon.
Histopathology
The histologic diagnosis depends on
identification of Reed-Sternberg (RS)
cell or their variants in the appropriate
background of reactive inflammatory
cells.
Reed-Sternberg (RS) is a large cell (15-45 m in diameter)
with an enlarged multilobated nucleus, prominent nucleoli and
abundant usually slightly eosinophilic, cytoplasm.
Characteristic cells have two mirrorimage nuclei, each containing a large
(inclusion-like) acidophilic nucleolus giving
owl-eye appearance.
The immunophenotype of the RS cell is
positive expression of CD15 & CD30.The
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reactive inflammatory cells include small

eosinophils, plasma cells and benign histiocytes

lymphocytes,

Reed-Sternberg cells and variants

Diagnostic Reed-Sternberg cell 1
Reed-Sternberg
cell,
mononuclear
variant 2
Reed-Sternberg cell, lacunar variant 3
Reed-Sternberg cell, lymphohistiocytic
(L&H) popcorn variant 4
Types of Hodgkin's lymphoma
Lymphocyte predominance; nodular H.L
2
Nodular sclerosis H.L.
Mixed cellularity H.L.
Lymphocyte depletion H.L
Lymphocyte rich H.L.
Types of Hodgkins lymphoma
1- Lymphocyte predominance nodular H.L
Common in male gender in the 4th
decade of life.
Microscopically:
Loss
of
nodal
architecture Diffuse infiltrate (with mature lymphocytes 3
admixed with histiocytes).
Classic RS cells are extremely difficult to find but instead
there is lympho-histiocytic (L&H) variant that have multilobed,
puffy nucleus similar in appearance to popcorn ("popcorn cell").
Excellent prognosis
2- Nodular sclerosis
The most common subtype of Hodgkin lymphoma
Adolescent or young
Equally in men and women
Dense collageneous bands subdivide the lymphoid tissue in to
circumscribed nodules.
Varying proportions of lacunar cells and lymphocytes.
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 Excellent prognosis
3- Mixed cellularity
This is the most common form in patients older than the age
of 50 year
Typical RS are plentiful
Mixed celluar infiltrate (eosinophils, plasma cells, and
histiocytes).
The prognosis is intermediate
4- Lymphocyte Depletion
Uncommon pattern, affects older patients.
Paucity of lymphocytes and relative abundance of RS
(anaplastic).
Mixed cellular infiltrate.
Very poor prognosis
5- Lymphocyte rich H.L.
It can occur at any age, and is more common in men than in
women
Lymphocyte-rich type
Excellent prognosis
The clinical and pathological stage are of clinical importance
Stages of H.D
Staging of Lymphomas (Ann Arbor classification)
Stage I: Involvement of a single lymph node region (I) or
involvement of a single extralymphatic organ or tissue (IE)
Stage II: Involvement of two or more lymph node regions on the
same side of the diaphragm alone (II)
Stage III: Involvement of lymph node regions on both sides of the
diaphragm (III), which may include the spleen (IIIS)
Stage IV: Multiple or disseminated foci of involvement of one or
more extra lymphatic organs or tissues
All stages are further divided on the basis of the absence (A) or
presence (B) of the systemic symptoms
The systemic symptoms include significant fever, night sweats,
and unexplained loss of more than 10% of body weight.
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-------------------------------------------------------------The WHO Classification of Lymphoid Neoplasms

Based on morphologic, phenotypic, genotypic, and clinical features
Precursor B-Cell Neoplasms
Precursor B-cell leukemia/lymphoma (B-cell ALL)
Peripheral B-Cell Neoplasms
B-cell chronic lymphocytic leukemia/small lymphocytic
lymphoma (CLL)
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Mantle cell lymphoma
Follicular lymphoma
Extranodal marginal zone lymphoma (MALT lymphoma)
Splenic marginal zone lymphoma
Nodal marginal zone lymphoma
Hairy cell leukemia
Plasmacytoma/plasma cell myeloma
Diffuse large B-cell lymphoma
Burkitt lymphoma
Precursor T-Cell Neoplasms
Precursor T-cell leukemia/lymphoma (T-cell ALL)
Peripheral T-/NK-Cell Neoplasms
T-cell prolymphocytic leukemia
T-cell granular lymphocytic leukemia
Mycosis fungoides/Szary syndrome
Peripheral T-cell lymphoma, not otherwise specified (NOS)
Angioimmunoblastic T-cell lymphoma
Anaplastic large-cell lymphoma, primary systemic type
Enteropathy-type T-cell lymphoma
Panniculitis-like T-cell lymphoma
Hepatosplenic T-cell lymphoma
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Adult T-cell lymphoma/leukemia (HTLV1)

K/T-cell lymphoma, nasal type
NK-cell leukemia
Hodgkin Lymphoma
----------------------------------------------------------------------Non Hodgkin Lymphoma (NHL)
Characters of NHL
NHL may be indolent or aggressive in behavior.
They interfere with the immune system
by dysregulating the function of normal B
and T cells.
They
often
contain
chromosomal
translocations or mutations involving
genes that regulate development and
survival
More frequent involvement of multiple peripheral node
Non contiguous spread
Mesenteric nodes and Waldeyer ring commonly involved
Extra-nodal involvement is common
Follicular Lymphoma
40% of adult lymphomas of B cell
phenotyping.
It usually involves lymph nodes, marrow,
and spleen.
The growth pattern is mainly nodular &
formed of small "cleaved" cells& large cell.
It is associated with t(14;18) with BcL-2 over expression by
mature B cells
Small Lymphocytic Lymphoma / Chronic Lymphocytic Leukemia
3%
of adult lymphomas, 30% of all
leukemias, indolent course
Occurs in older adults usually involves
nodes, marrow, and spleen.
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 Most patients have peripheral blood involvement

Diffuse effacement by small rounded lymphocytes
CD5+B-cell expressing surface Ig.
Diffuse Large B-Cell Lymphoma
50% of lymphomas; aggressive course
Occurs in all ages; often arise at
extra-nodal sites
Highly
associated
with
rearrangements or mutations of
BCL6 gene.
Transformed lymphoid cells with
vesicular nuclei and mitotic figures
B cells with variable expression of
CD10 and surface Ig
Burkitt Lymphoma
Endemic in Africa, sporadic elsewhere, often presents at
extranodal sites with visceral
involvement, predominantly affects
children.
It is associated with translocations
involving the c-MYC proto-oncogene
and is often associated with
infection by Epstein-Barr virus.
Highly aggressive tumor of B cells
formed of diffuse involvement by
intermediate-sized cells, excess mitoses & a "starry-sky"
appearance.
Immunophenotyping expression of CD10+B cells & surface Ig.
Peripheral T-cell lymphoma
Most common adult T-cell lymphoma.
Often disseminated, generally aggressive.
Spectrum of small to large lymphoid cells
with irregular nuclear contours.
CD3+mature T-cell phenotype.
Mycosis fungoides
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 Most common cutaneous lymphoid

malignancy, generally indolent.
Presents with localized or more
generalized skin involvement.
Small
lymphoid
cells
often
infiltrate the epidermis (Pautrier
microabscesses)
CD4+mature T cells.
Szary syndrome:
a more
aggressive variant
characterized by diffuse skin
erythema and peripheral blood
involvement.
Myeloid Neoplasms
They arise from hematopoietic stem cells
that give rise to cells of the myeloid (i.e.,
erythroid,
granulocytic,
and/or
thrombocytic) lineage.
Classification:
1) Acute myelogenous leukemias, in which
immature progenitor cells accumulate in the
bone marrow.
2) Myelodysplastic syndromes, which are
associated with ineffective hematopoiesis
and peripheral blood cytopenias.
3)

Chronic

myeloproliferative

disorders

(MPDs), which are associated with an increased production of

terminally differentiated myeloid cells (e.g., granulocytes) &
elevated peripheral blood counts.
Chronic myelogenous leukemia
Polycythemia vera
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 Essential thrombocytosis
Primary myelofibrosis
All four have some similar features. The neoplastic stem
cells have the capacity to circulate and they give rise to
extramedullary hematopoiesis. As a result, all chronic MPDs
cause varying degrees of splenomegaly. They also terminate
by marrow fibrosis and peripheral blood cytopenias.
Further, all can progress over time to acute leukemia.
Acute Myelogenous Leukemia (AML)
Acute myelogenous leukemias affect primarily adults between the
ages of 15 and 39 years.
Classification :
The revised FAB divided AML into eight (M0 to M7)
categories according to the degree of maturation (M0 to M3)
and the lineage of the leukemic blasts (M4 to M7).
The WHO classification retains the FAB categories M0 to M7
but also creates special categories for AMLs associated with
particular chromosomal changes.
Morphology:
Myeloid blasts make up more than 20% of the cells in the bone
marrow.
Myeloblasts have delicate nuclear chromatin, two to four
nucleoli, more voluminous cytoplasm than lymphoblasts.
The cytoplasm often contains Auer rods, which represent
peroxidase-positive granules & it is definitive evidence of
myeloid differentiation.
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 Monoblasts have folded or lobulated nuclei, lack Auer rods&

non specific esterase positive.
Immunophenotype: by staining cells for myeloid-specific markers.
Cytogenetics and Molecular Genetics: Most AMLs are associated
with acquired genetic translocation that disrupts genes encoding
transcription factors needed for normal myeloid differentiation
with blast cell accumulation. T (8;21), T(15;17) chromosomal
translocation.
Clinical Features: (less striking in AML than in ALL)
Fatigue, fever, cutaneous petechiae and ecchymoses.
Infections, mild lymphadenopathy and organomegaly.
Chloromas: Localized masses composed of myeloblasts in the
absence of marrow or peripheral blood involvement may
progress to systemic AML within several years.
Prognosis: Approximately 60% of the patients achieve complete
remission with chemotherapy. Only 15% to 30% remain free from
disease for 5 years.
Acute Lymphoblastic Leukemia (ALL)
ALL are neoplasms composed of immature, precursor B (pre-B) or
T (pre- T) lymphocytes referred to as lymphoblasts.
ALL is twice common in whites than in non whites and more
frequent in boys than in girls.
The majority of ALLs are precursor B-cell tumors that
typically manifest about the age of 4 as childhood acute
"leukemias" with extensive bone marrow and blood
involvement.
The less common precursor T-cell ALLs tend to present in
adolescent males as "lymphomas" often with mediastinal
thymic involvement.
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Morphology: Lymphoblasts have condensed chromatin, small

nucleoli & scant agranular cytoplasm.
Histochemical stains of lymphoblasts revealed lack of peroxidasepositive granules and prescence of periodic acid-Schiff (PAS)positive material.
Immunophenotype :
Immunostaining for terminal deoxy nucleotidyl transferase (TDT) is
positive in >95% of cases.
Distinction between ALLs of precursor B- and T-cell origin requires
specific markers.
Cytogenetics and Molecular Genetics: Approximately 90% of
patients with ALL have numerical or structural changes in the
chromosomes of the leukemic cells. Most common is hyperploidy,
but also polyploidy, and t (12;21) and t (4;11) translocations.
Clinical Features:
Abrupt stormy onset
Fatigue, fever, bleeding (petechiae, ecchymoses, epistaxis,
gum bleeding)
Bone pain and tenderness
Generalized
lymphadenopathy,
splenomegaly,
and
hepatomegaly more common in ALL
Central nervous system manifestations also more common in
ALL than in AML.
Testicular involvement is more common in ALL
Prognosis: More than 90% of children with ALL achieve complete
remission & at least two thirds can be considered cured

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Chronic Myelogenous Leukemia (CML)

Chronic myelogenous leukemia is a disease primarily of adults
between the ages of 25 and 60 years with the peak incidence in the
fourth and fifth decades of life.
Morphology :
In contrast to normal bone marrow, which is usually about 50%
cellular and 50% fat,
B.M in CML is usually 100% cellular, with excess maturing
granulocytic precursors.
Increased megakaryocytes & increased reticulin fibers are
typical.
A characteristic finding is the presence of scattered storage
histiocytes.
Peripheral blood examination:
There is a reciprocal (9;22)(q34;q11) translocation.
The resultant BCR-ABL fusion gene directs the synthesis of
fusion protein with tyrosine kinase activity. It reveals a
marked leukocytosis, often exceeding 100,000 cells per mm3.
The circulating cells are predominantly neutrophils,
metamyelocytes, and myelocytes, with less than 10%
myeloblasts.
Chromosomal Abnormalities and Molecular Genetics :
CML is distinguished from other chronic MPDs by the
presence of a translocation involving the BCR gene on
chromosome 9 and the ABL gene on chromosome 22.
In more than 90% of CML cases, karryotyping reveals the socalled Philadelphia chromosome (Ph)
Clinical Features: The onset of CML is insidious with mild anemia,
weakness, weight loss, and anorexia.
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 Marked splenomgaly or left abdominal pain due to splenic

infarction.
Prognosis: Slow progression and even without treatment. The
median survival is 3 to 4 years.
Chronic Lymphocytic Leukemia (CLL/SLL)
Most patients present at ages over 50 (median age 60); a male
predominance has been noted (M: F ratio of 2:1).
CLL/SLL are morphologically, phenotypically, and genotypically
indistinguishable, differing only in the degree of peripheral
blood lymphocytosis.
CLL patients have sufficient lymphocytosis (absolute
lymphocyte count >4000 per mm3).
Morphology:
Lymph node architecture is diffusely effaced by a
predominant population of small lymphocytes containing round
nuclei with condensed chromatin and scant cytoplasm.
These cells are mixed with variable numbers of larger cells
called "prolymphocytes that may form proliferation centers
that are pathognomonic for CLL/SLL.
Peripheral blood examination :
CLL show increased numbers of small, round lymphocytes with
scant cytoplasm. These cells are fragile and are frequently
disrupted, producing smudge cells.
Involvement of the bone marrow is observed in all cases of
CLL and most cases of SLL.
Immunophenotype:
CD19 and CD20.

CLL/SLL express the pan B-cell markers

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Chromosomal Abnormalities and Molecular Genetics Chromosomal

translocations are rare in CLL/SLL. The most common findings are
deletions of 13q12-14, deletions of 11q, trisomy 12q, and deletion of
17.
Clinical Features :
Patients are often asymptomatic.
When symptoms appear, they are non specific and include easy
fatigability, weight loss, and anorexia.
Generalized lymphadenopathy and hepatosplenomegaly are
present in 50% to 60% of the cases.
Prognosis: It is variable and depend on the clinical stage. The
median survival is 4 to 6 year

SPLENOMEGALY
A. Massive splenomegaly (weight more than 1000 gm)
1. Chronic myeloproliferative disorders & chronic leukemia
2. Hairy cell leukemia
3. Lymphomas
4. Malaria & Gaucher disease
5. Primary tumors of the spleen (rare)
B. Moderate splenomegaly (weight 500-1000 gm)
1. Congestive splenomegaly
2. Leukemias
3. Autoimmune hemolytic anemia
4. Amyloidosis
5. Niemann-Pick disease
6. Langerhans histiocytosis
7. Chronic splenitis
8. Tuberculosis, sarcoidosis
C. Mild splenomegaly (weight <500 gm)
1. Acute splenitis
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2. Acute splenic congestion

3. Infectious mononucleosis
4. Acute febrile disorders e.g. septicemia & SLE
Hypersplenism
Enlargement of spleen occurs with anemia, leukopenia, and
thrombocytopenia due to increased sequestration and
destruction of these cells in the spleen.
Hyposplenism
It follows splenectomy. It is diagnosed by circulating red
cells containing nuclear debris.
It may also occur in amyloidosis, sickle cell disease &
autoimmune diseases.

( THANK YOU & GOOD LUCK)

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