L:3

Myelodysplastic Syndrome[(MDS)or Preleukemia]

*Characterized by : Dysmyelopoiesis(=cells+ impaired maturation).

Peripheral blood cytopoenias.

●Clonal disorders including stem cell+ chromosomal abnormality.

*FAB((French, American, British)) classification:

Based on the presence of Dysmyelopoiesis

Quantification of Myeloblasts

Erythroblasts.

1) Refractory anemia (RA):

●Anemia.

●< 5% blasts.

●< 15% sideroblasts.

2) Refractory anemia with ringed sideroblasts (RARS):

●> 15% sideroblasts.((seen by Prussian blue stain)).

3) Refractory anemia with excess blasts (RAEB):

●5-20% myeloblasts and promyeloblasts.

4) Refractory anemia with excess blasts in

transformation (RAEBIT):

●21-29% blasts…………>30% blasts → acute leukemia.

5)Chronic myelomonocytic leukemia(CMML):

●Elevated WBCs.

●Persistent monosytosis.

●Splenomegaly.

:

dd. with CML In CMML: No Philadelphia[[t(9:22)]] chromosome.

In CMML: Trilineage dysplasia→ RBC→ anemia

WBC→infection

Platelets→ bleeding

●CMML transformed to Acute nonlymphocytic leukemia(ANLL) when blasts exceeds 30%.

*Management:

1) Supportive treatment:→ Packed cell transfusion.

Antibiotics.

Platelets transfusion.

2) Cytotoxic(antileukemic)chemotherapy.

3) B.M. Transplantation OR

Recombinant growth factors GM-CSF

G-CSF

Erythropoietin

Neoplasm of plasma cells

*Neoplasm of plasma cells→ B-lymphocytes(responsible for secreting ↓↓ Ig).

abnormal Ig = Para protein.

((So, paraprotein is abnormal Ig result from neoplasm of plasma cells)).

*3 Major groups are recognized:

a) Monoclonal gammopathy of uncertain significance(MGUS).

b) Multiple Myeloma.

c) Macroglobulinemia.

(Plasma cell Myeloma) Multiple Myeloma

* Incidence:

●1-2 cases/100,000 population.

●♂ > ♀ .

* Clinical Presentation:

a) Multiple osteolytic bone lesions(in skull and other bones) due to:

hypercalcemia. Common complaint is back pain.

b) Weakness and fatigue due to: B.M. suppression and anemia.

c) Renal impairment due to:

-toxic effects of filtered light chains,

-hypercalcemia,

-amyloid deposits.

d) Serious infections secondary to:

hypogammaglobulinemia and neutropenia.

e) Elevated levels of serum β2 microglobulin.

((بتحديد levels of serum β2 microglobulin نستطيع تعيين مرحلة المرض)).

*Diagnosis:

1) Presence of monoclonal immunoglobulin >3g/dl.

2) At least 10% plasma cells in B.M.

*Clinical staging:

Stages I,II,III according to levels of M(myeloma or macroglobulinemia) component.

In Stage I: -little radiologic disease.

-Normal serum calcium.

Stage III: -Extensive bone disease.

-Hypercalcemia.

* Treatment:

a) If pt is symptomatic or the myeloma shows signs of progression, such as increasing serum or urine levels of M component, renal insufficiency or anemia.

1)Chemotherapy:

a)Alkalyting agents such as melphalan.

b)Steroids such as prednisone.

2)Radiation therapy:

for local treatment of pathologic fractures.

3)B.M. transplantation.

b)Response to treatment is monitored by:

-serum levels of M component.

-β2 microglobulin levels.

((if the pt response to treatment the serum level of M component and β2microglobulin levels are low. If there is no response to treatment the levels are still as it or become high)).

Macroglobulinemia

Macroglobulinemia→ Essential(Benign)macroglobulinemia.

→ Plasmacytoid B cell lymphoma.

→ Waldenström΄s macroglobulinemia.

*Diagnosis:

●In essential macroglobulinemia→ ●Asymptomatic.

●Low levels of IgM para protein.

●In Waldenström΄s macroglobulenimemia→Levels of the M component >3g/dl.

●Organomegaly.

●Hyper viscosity Syndrome.

●Anemia.

*Clinical presentation:

a)Weight loss, fatigue and mild bleeding(as epistaxis).

b)B.M.: lymphoplasmacytic and plasma cells which are also present in peripheral blood. Lymphadenopathy and Splenomegaly are common.

c)Monoclonal IgM present cause:

((level of M component >3g/dl)) Hyper viscosity Syndrome:

a)Generalized neurologic dysfunction→ Coma.

b)A bleeding due to impaired platelet function.

c)Generalized hypervolemia→ Congestive heart failure.

d)Renal changes: hemorrhages and papilledema.

Amyloidosis

Extravascular deposition of proteinaceous material.

1)Primary amyloidosis due to:

the deposition of monoclonal immunoglobulin light chains, usually in the heart, tongue, GIT, liver, and connective tissue.

2)Secondary amyloidosis due to:

the deposition of amyloid A protein mainly in the liver, spleen, adrenals, and kidney, and is associated with chronic inflammatory diseases such as rheumatoid arthritis, osteomyelitis, tuberculosis, and carcinoma.

3)Familial amyloidosis:

are caused by specific genetic mutations in a variant prealbumin protein(seen by electrophoresis) called transthyretin.

Neoplastic Disorders Of Monocytes & Histocytes

-Malignant histocytosis.

-True histocytic lymphomas:

+ve cytochemical and immunological markers of monocytic origin.

((ذكرأسماء فقط)).

Malignant Lymphoma

Malignant Lymphoma:→ Hodgkin's

→ Non hodgkin's.

*Introduction:

●Incidence: 5-10 cases/100,000 population((in one year)).

2:1 non hodgkin's : hodgkin's

3:2 ♂ : ♀

●Etiology:

a)Infections and viruses:

-HTLV-1 with acute T cell lymphoma/leukemia.

-EBV with Burkitt's lymphoma.

b)Immunologic dysfunction:

-AIDS.

-Autoimmune disorders.

c)Heredity.

d)Chemical:

-Farmers exposed to herbicides.

-Benzene.

*Diagnosis:

Hodgkin's and Non Hodgkin's are differ in staging, treatment and prognosis.

*Treatment:

-Radiation.

-Combination of radiation and chemotherapy.

*Staging of Lymphomas:

Hodgkin's disease:

*Clinical presentation:

-Early adulthood.

-Spread from one lymphoid region to the next.

-Defect in cellular immunity : increase susceptibility to infection.

*Diagnosis:

Red-Sternberg (RS) cells((most characteristic cell for diagnosis of Hodgkin's lymphoma under the microscope)):

Large cell with two or more nuclei demonstrating prominent central nucleoli.

*Subtypes: Nodular sclerosis, lymphocyte predominant, mixed cellularity and lymphocyte depleted((these case has poorest prognosis)).

*Prognosis:

90% of pt cure. (poorest prognosis).

*Treatment:

-Radiation.

-Chemotherapy.

Non hodgkin's disease:

*pathology:

a)Anatomic, phenotypic, proliferative, and functional characteristics:

-Lymphomas of morphologically mature cells.

-Non Hodgkin's lymphomas of larger and less mature cells.

-65% -75% of lymphomas are of B lymphoid origin, and 25% - 35% are of T lymphoid origin.

-Lymphomas of mature B cells may produce immunoglobulin paraproteins while tumors of mature T cells may be associated with hypergammaglobulinemia.

b)Pattern and cell type Indolent tumors: small mature cells((low grade))

Aggressive tumors: diffuse large less- differentiated cells((high grade))

c)Histologic progression : low grade or high grade tumors.

*Clinical presentation:

-Enlarged painless lymph nodes.(Cervical, inguinal, and axillary).

-Extranodal sites(in high grade lymphomas)such as GIT, skin, salivary glands, and bones.

*Subtypes:

a)Lymphoplastic lymphoma is the tissue equivalent of ALL: usually of T lymphocyte origin.

b)Small noncleaved(Burkitt's) lymphoma:

-association with EBV.

-always of B cell origin.

c)Intermediate differentiation lymphomas.

d)Cutanenous T cell lymphomas such as mycosis fungoides also in Sézary syndrome diffuse erytheroderma

mycosis fungoides

circulating lymphoma cells.

((treatment as we said as general in lymphoma: radiation or chemotherapy, or combination b/w radiation and chemotherapy)).

انتهى بفضل الله...

1

Dr.Ashwag B. Alshareif