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