Transcript الشريحة 1

The Non-Leukaemic Lymphoproliferative Disorders
Ahmad Sh. Silmi
Msc Hematology,
FIBMS
IUG
The Non-Leukaemic Lymphoproliferative
Disorders
These are malignant clonal disorders of the
lymphopoietic system and include:
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Multiple Myeloma and Related Plasma Cell Disorders
HD
NHL
Multiple Myeloma and Related Plasma Cell Disorders
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Multiple Myeloma (MM) is a B lymphoid malignancy
which, is characterized by the proliferation of a
malignant clone of plasma cells which synthesize
and secrete excessive amounts of monoclonal
immunoglobulin. In many respects, MM behaves as
a solid tumour with a prior involvement for bone
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Incidence
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Disease of elderly.
The median age at diagnosis is about 62
years.
The disease is more common in blacks
than in whites.
The disease shows slight excess
incidence in male than female.
Pathophysiology
Lytic Bone Lesions
Pathologic Fractures
Hypercalcemia
Palpable Plasmacytoma
Pancytopenia
Skeletal Destruction
Anaemia
infection
bleeding
Marrow Infiltration
Malignant Proliferation
Of Plasma Cells
Abnormal proteins
(immunoglobulins)
Decreased in the
amount of normal (Igs)
Clinical symptoms
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bone pains, pathologic fractures
weakness and fatigue
serious infection
renal failure
bleeding diathesis
Laboratory tests
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ESR > 100
anaemia, thrombocytopenia
rouleaux in peripheral blood smears
marrow plasmacytosis > 10 -15%
hyperproteinemia
hypercalcemia
proteinuria
azotemia
Diagnostic Criteria for Multiple Myeloma
Major criteria
I. Plasmacytoma on tissue biopsy
II. Bone marrow plasma cell > 30%
III. Monoclonal M spike on electrophoresis IgG > 3,5g/dl,
IgA > 2g/dl, light chain > 1g/dl in 24h urine sample
Minor criteria
a. Bone marrow plasma cells 10-30%
b. M spike but less than above
c. Lytic bone lesions
d. Normal IgM < 50mg, IgA < 100mg, IgG < 600mg/dl
Diagnostic Criteria for Multiple Myeloma
Diagnosis:
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I + b, I + c, I + d
II + b, II + c, II + d
III + a, III + c, I II + d
a + b + c, a +b + d
Staging of Multiple Myeloma
Clinical staging
 is based on level of haemoglobin, serum calcium,
immunoglobulins and presence or not of lytic bone lesions
 correlates with myeloma burden and prognosis
I. Low tumor mass
II. Intermediate tumor mass
III. High tumor mass
 subclassification
A - creatinine < 2mg/dl
B - creatinine > 2mg/dl
Poor prognosis factors
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cytogenetical abnormalities of 11 and 13
chromosomes
beta-2 microglobulines > 2,5 ug/ml
Treatment
At present, there is no curative therapy, but
symptomatic treatment may be as:
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Blood transfusion if anaemia present.
Antibiotic to treat infection.
Local radiotherapy for osteolytic bone.
Dialysis in case of renal failure.
Alkalating agents may provide pain relief, but the
response to these drugs is slow.
Waldenstrom's Macroglobulinaemia
Waldenstrom's Macroglobulinaemia
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Waldenstrom's Macroglobulinaemia (WM) is
an uncommon B lymphoid disorder, which is
characterized by hyperviscosity secondary to
the excessive secretion of a monoclonal IgM
immunoglobulin by the malignant clone.
Causes
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It is caused by the loss of regulation of a
clone of cells, which appear to be in an
intermediate stage of development between
the mature lymphocytes and the early
plasma cells. Morphologically, the malignant
cells of WM are rather more immature than
those in MM and frequently are described as
being "lymphoplasmacytoid".
Incidence
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WM is a disease of elderly, with a peak
incidence occurring in the seventh decade of
life with no sex predilection.
Life expectancy ranges from 8 months to 8
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Symptoms
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Weight loss.
Hepatosplenomegaly.
Lymphadenopathy.
bruising or bleeding tendency.
A long history of vague weakness, fatigue and
weight loss.
Hyperviscosity syndrome due to malignant infiltration
or accumulation of monoclonal immunoglobulin.
Clinical symptoms
Accumulation of the IgM can lead to a variety of clinical symptoms
include:
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Neurological symptoms such as headache, vertigo, and in severe
cases coma.
Visual disturbances secondary to retinal haemorrhage and oedema,
which may cause permanent blindness.
Cardiac failure which is severe by the increased plasma viscosity.
Platelet dysfunction secondary to coating of the platelets by the
monoclonal IgM.
Haemostatic disturbances secondary to the inhibition of fibrin
polymerization and factor VIII activity by the monoclonal IgM.
Laboratory Findings
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Normocytic normochromic anaemia secondary to suppression of
erythropoiesis by the malignant clone.
Rouleaux formation secondary to hyperviscosity.
Chronic bleeding and dilution by the increased plasma volume.
The WBC may be normal or depressed but a relative
lymphocytosis commonly is present.
The platelet count is normal at presentation. However,
neutropenia and thrombocytopenia become more severe as the
disease progress.
Hypercellular and extremely hyperviscous bone marrow, which
makes attempts to aspirate the bone marrow frequently difficult.
The malignant cells are pleomorphic: some resembles
lymphocytes whereas others clearly resemble plasma cells;
most, however, have an intermediate appearance and are
described as being lymphoplasmacytoid.
Prognosis
Depends on the pattern of infiltration of the malignant clone in the
bone marrow:
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Diffuse infiltration is associated with poor prognosis, with
a median survival of 17 months.
Nodular infiltration is associated with a much better
prognosis, with a median survival of 72 months.
The intermediate form of infiltration, which shows features
of both nodular and diffuse infiltration, is associated with a
median survival of 52 months.
Treatment
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Symptomatic relief from hyperviscosity syndrome is
achieved mostly by repeated plasmapheresis.
Progressive disease is treated with chemotherapy.
Hodgkin's Disease
Hodgkin's Disease
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Hodgkin's disease (HD) is a neoplastic
disorder with development of specific
infiltrate containing pathologic ReedSternberg cells. It usually arises in lymph
nodes and spreads to contiguous groups.
Extranodal presentation are rare. Disease
is associated with defective cellular
immunity.
Incidence
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2-4 cases per 100000 population / year
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bimodal age distribution :
15-35 years and above 50 years
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male predominance
M:F = 1,7:1
Pathophysiology
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The most common presenting feature in HD is the
presence of painless, a symmetrical enlargement of
cervical or supraclavicular lymph nodes. Axillary, inguinal
or femoral lymphadenopathy also is seen occasionally.
The lymphadenopathy may be accompanied by severe,
generalized itching in the absence of skin rash.
In contrast to non-Hodgkin's lymphomas, which frequently
are disseminated at presentation, most cases of HD are
restricted to a single anatomical site at presentation.
The presence of pyrexia and night sweats usually are
associated with more advanced disease.
Clinical Presentation
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Nontender lymph nodes enlargement ( localised )
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systemic symptoms (B symptoms)
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neck and supraclavicular area
mediastinal adenopathy
other ( abdominal, extranodal disease )
60-80%
50%
30%
fever
night sweats
unexplained weight loss (10% per 6 months)
other symptoms
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fatigue, weakness, pruritus
cough , chest pain, shortness of breath, vena cava syndrome
abdominal pain, bowel disturbances, ascites
bone pain
Recognition
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The peripheral blood is entirely normal at presentation.
Occasionally, mild non-specific changes such as; a mild
thrombocytosis, neutropenia or relative eosinophilia is present.
The presence of anaemia, lymphocytopenia or leucoerythroblastosis
all suggest the presence of advanced disease with bone marrow
involvement, but this is uncommon at presentation.
The disease is recognized by histological examination of an affected
lymph node biopsy, which reveals the presence of a diffuse infiltrate of
lymphocytes, histiocytes, and eosinophil, plasma cells and neutrophils,
which are of normal appearance. Scattered among this infiltrate are
variable numbers of Reed-Sternberg (RS) cells, the characteristic
feature of HD.
The presence of RS cells is not specific for HD, they also are present
in some cases of infectious mononucleosis, NHL, and CLL but their
demonstration is required for a diagnosis of HD.
RS cells typically are large, with two or more large, oval nuclei, each of
which contains a huge nucleolus, which is separated from the
thickened nuclear membrane by a clear zone.
Classification
On the basis of the pattern of the lymph node
infiltration, four subtypes of HD are
recognized:
Lymphocyte predominant HD (LPHD)
is characterized by:
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A heavy infiltrate of small lymphocytes and
histiocytes which have a normal morphology.
The infiltrate is diffuse but may form loose nodules.
RS cells usually are sparse.
This subtype of HD is common in young men.
It's associated with a rapid response to treatment
and good prognosis.
Nodular sclerosing HD (NSHD)
Involves:
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Nodular sclerosis and the presence of classical RS cells, as
well as a distinctive RS cell variant called Lacunar cell in
which the cell cytoplasm has contracted as an artifact of
fixation, leaving an unstained zone between it and the
surrounding tissue.
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Sclerosis is found in the form of well-organized bands of
collagen that subdivides the tissue into distinct nodules.
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NSHD is the most common subtype, accounting for more
than 40% of cases.
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It appears to be commonly associated with a thymic origin
and offers a fairly good prognosis.
Mixed cellularity HD (MCHD)
is characterized by:
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The presence of large numbers of typical
and mononuclear RS cells, scattered
among morphologically normal
lymphocytes, histiocytes, neutrophils,
eosinophils, plasma cells and fibroblasts.
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This subtype of HD is associated with a
less favorable prognosis than either of the
above subtypes.
Lymphocyte depleted HD (LDHD)
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Large numbers of RS cells and atypical
histiocytes, scanty lymphocytes and
variable fibrosis.
This subtype is the least common form of
HD, and is associated with elderly
subjects, who often present with advanced
disease and have a poor prognosis.
Immunophenotyping
The consistent antigenic markers on RS cells
include:
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CD25, the IL-2 receptor, CD15 and CD30.
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The NSHD and MCHD are more commonly
associated with B lymphoid markers while
LPHD is associated with T lymphoid markers.
Staging of Hodgkin's Disease
Stage
I
Definition
Involvement of single L.N region
II
Involvement of 2 or more L.N groups on the same side of the
diaphragm
Involvement of L.N regions on both sides of the diaphragm
III
IV
Diffuse or disseminated involvement of 1 or more
extralymphatic organs or tissues with or without associated
L.N involvement
Treatment
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According to the stage of disease, early
stage requires localized radiotherapy to the
involved lymph nodes, while advanced stage
involve the use of combination chemotherapy
with or without radiotherapy.
Prognosis
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With modern treatment, more than 80% of
cases of stage I HD and more than 50% of
stage IV HD survive for more than 10 years
after presentation. Most of these can be
considered to be cured.
Non-Hodgkin Lymphoma
Aetiology
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Possible infectious aetiology secondary to EBV. This virus
induces chronic suppression of the immune system, such as
occurs in AIDS. Recent evidence has suggested that
reactivation of EBV is associated with an increase incidence
of NHL.
Epidemiological studies have shown a small excess of NHL
among agricultural workers and rubber industry workers but
the significance of this observation remains in doubt.
Cytogenetic abnormalities are present in almost all cases of
NHL. The most common chromosomal rearrangement often
involves chromosome2, 3, 7, 12, 14 and 18.
Pathophysiology
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Lymphomas with a follicular pattern of growth are
less aggressive than those with a diffuse pattern
of growth.
Small lymphocytic lymphomas are less
aggressive than large cell lymphomas.
In common with acute leukaemias, some forms of
high-grade lymphoma are more amenable to
treatment than the chronic types.
In contrast to HD, most NHL is disseminated to a
greater or lesser extent at presentation.
Classification
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Low Grade Lymphoma
Intermediate Grade Lymphoma
High Grade Lymphoma
Treatment
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Lymphomas with a follicular pattern of growth are
less aggressive than those with a diffuse pattern
of growth.
Small lymphocytic lymphomas are less
aggressive than large cell lymphomas.
In common with acute leukaemias, some forms of
high-grade lymphoma are more amenable to
treatment than the chronic types.
In contrast to HD, most NHL is disseminated to a
greater or lesser extent at presentation.