Summarize the following text to main points and sub-points and make detailed explain for them:

tiate it from AML), TDT terminal 
deoxyNucleotide transferase.
complete remission can be achieved with chemotherapy 
in about (80- 90%) of children.
Acute myeloblastic leukemia (AML).
Neoplastic proliferation of myeloblast.
characterized by greater than 20% myeloid blasts and is the most 
common acute leukemia in adults.
usually affect  individuals aged between 15-40years.
Myeloblast have oval to round nucleus , immature fine 
chromatin, prominent nucleoli ,  moderate amount of  in 
cytoplasm which stains positive for myeloperoxidase. (N.B 
negative for TDT).
(Auer rods), intracytoplasmic rod like structure in some cases.
Philadelphia chromosome (BCR22-ABL 9 fusion gene): 
genetic abnormality in chromosome 22 of leukemic 
cancer cells in CML.
The Philadelphia chromosome forms when 
chromosome 9 and chromosome 22 break and 
exchange parts.
CML have three phases:”
Chronic phase (80%) ,Asymptomatic , most pt
diagnosed here.
Accelerated phase (20%) splenomegaly & basophilia.
Blast phase clinically behave like acute leukemia.
CML can transform into Acute leukemia (AML or 
ALL).
Chronic lymphatic leukemia
CLL occurs from the proliferation of monoclonal lymphoid cells. 
Most cases occur in people between the ages of 60 and 70. 
is considered an indolent disease, for the most part, meaning not 
all patients with a diagnosis will need to start treatment until 
symptomatic from the disease.
C/P: generalized enlargement in  lymph nodes commonly in the 
cervical L.Ns, liver & spleen enlargement.
CLL is lymphocytosis in peripheral blood and bone marrow.
Classical "smudge" cells ("basket" cells) are also seen on 
peripheral blood smear; and are pathognomic of CLL, these cells 
reflect fragility or vulnerability to distortion of B-CLL cells upon 
mechanical manipulation.
Autoimmune hemolytic anemia may occur in 20% .  
Pathology of leukemia
1)
Bone marrow: leukoblastic reaction seen mainly in sternum, ribs, vertebrae, pelvis & ends of long 
bones, appears reddish brown in acute leukemia & grayish white in chronic leukemia.
2)
Blood changes: 
I.
Increase in leukocytic count .
II.
blast cells predominate  in acute leukemia
III.
in chronic leukemia differentiated cells are seen as ( myelocytes & leukocytes or lymphocytes).
IV.
Myelophthisic anemia in chronic leukemia.
V.
Thrombocytopenia can occurs and causes hemorrhage in tissues.
(3) leukemia infiltrate seen in different organs as liver, adrenal, kidney, heart , GIT, skin, gums.
(4) Lymph nodes show leukemic infiltration causing enlargement of nodes & loss of normal architecture. 
(5) Splenomegaly occurs due to leukemic infiltration of spleen. Splenic infarcts due to thrombosis of its 
vessels.
Laboratory findings of leukemia :
Blast cells in peripheral blood, and B.M (>20% in 
acute leukemia, <10% in chronic leukemia).
WBC count variable, ranges from 100.000 cells/ & 
less than 10.000 cells/ .
anemia, neutropenia, thrombocytopenia platelet 
count less than 100.000 plt/.
metabolic disturbances: due to (tumor lysis 
syndrome= rapid breakdown of tumor cells) results 
in increase in k+, phosphate, hyperuricemia , & 
hypocalcemia lead to acute renal injury & cardiac 
arrhythmia.
Basophilia , & thrombocytosis are seen in CML.
Clinical manifestation of leukemia:
fever, anorexia, weight loss, symptoms of anemia 
(dyspnea, fatigue, weakness &  pallor of skin).
neutropenia, results in recurrent infections which 
is lethal.
thrombocytopenia leading to bleeding (petechia & 
bruising).
lymphadenopathy, hepatosplenomegaly can occur. 
CNS symptoms: headache, symptoms of raised ICP  
(nausea, vomiting & lethargy).
bone  & joint pain  due to the  build-up of 
cancerous white blood cells that causes the bone 
marrow to expand in size and put pressure on nerves 
within the bone tissue, causing bone pain.
skin changes (leukemia cutis), (papules, nodules, 
ulcers).
Histiocytic neoplasm
Langerhans Cell Histiocytosis (LCH)
rare disease that affects the body in various ways. It emerges from an excessive buildup and 
proliferation of Langerhans cells.
LC  normally helps the body fend off infections. In LCH, these cells accumulate and can form tumors or 
lesions in one or more organs of the body.
affect individuals of any age, especially children less than 2 yrs.
symptoms ranging from localized bone lesions to multiorgan involvement, such as bone pain, skin 
rash, and hepatosplenomegaly, anemia, thrombocytopenia & infections.
Treated with intensive chemotherapy.
50% of pt survive 5 years.
Bleeding disorders: 
Are group of disorders characterized by defective 
hemostasis with abnormal bleeding.
(hemo=blood), (stasis= standing still).
Bleeding can be:
Spontaneous.
or follow initial trauma.
bleeding can be grossly manifested in the form of :
petechia.
purpura.
ecchymosis / bruises.
hematoma.
Tests to evaluate bleeding disorders: 
1)
Bleeding time: time interval between puncture to blood vessel to the stoppage of bleeding (2-9min).
2)
PLT count 150-450x 10 cells/mm3, 
3)
Prothrombin time (PT): adequacy of extrinsic & common coagulation pathway.
4)
Partial thromboplastin time (PTT): adequacy of intrinsic & common clotting pathway.
1- Disseminated intravascular coagulation (DIC)
Causes:
1.
sepsis.
2.
Malignant tumors. 
3.
Trauma,  surgery.
4.
infections.
5.
burns & shock.
6.
obstetric complications (amniotic fluid embolism, post-partum hemorrhage, preeclampsia…etc).
IN DIC :  endothelial injury release tissue factors & 
expose sub endothelial collagen & vWF to promote
plt aggregation & activate intrinsic coagulation 
system.
The clinical sequelae of DIC are :
Bleeding, thrombosis or both.
Without adequate treatment, DIC can eventually 
lead to multiorgan dysfunction / failure.
(2) Thrombocytopenia
results from decreased production, or increased 
destruction.
spontaneous bleeding , prolonged BT, normal PT 
&PTT,  platelet count 100.000 cells/L.
one of the most common manifestations in AIDS.
A.
Immune thrombocytopenic purpura
• destruction of PLT, by presence of autoantibodies 
directed against PLt Ag, triggered by drugs, 
infections, lymphoma or it can be idiopathic .
• spleen produce Ab & destruction of Ig coated plt 
occur, spleen normal in size. 
•Patient can benefit from splenectomy.
(B) Heparin induced thrombocytopenia
HIT can occur in up to 5% of patients exposed to heparin products, usually after 1-2 weeks of treatment with 
heparin.
HIT causes an extremely hypercoagulable state, where up to 50% of patients develop thromboembolic 
complications, associated with a mortality rate of up to 30%.
caused by IgG antibodies bind to PLt cause its activation result in venous & arterial thrombosis.
(C) Vonwillbrand disease (vWB)
is the most common inherited bleeding disorder.
autosomal dominant, caused by mutation in vWF, that acts as bridging molecules between pLt & 
subendothelial collagen.
vWF stabilizes factor VIII by binding to it.
C/P: easy bruising, epistaxis, bleeding from the gum, post dental / post surgical procedure bleeding, 
menorrhagia.
diagnosis: normal platlet, slight increase in PT & PTT, 
measuring factor VIII, and VWF  antigen.
Clinical manifestation of Hemophilia A & B  
-Male are more affected.
- C/P: 
- (bleeding either spontaneous or after trauma). 
-spontaneous intracranial bleeding in neonates, 
-excessive postoperative bleeding after 
circumcision.
-Hemarthrosis manifests as the most common 
hemorrhagic symptom in adolescents and 
adults.
- PTT is prolonged., while  PT normal .
Splenomegaly: enlargement of spleen secondary to 
systemic disease.
- moderate splenomegaly (500-1000gm)
1.
Portal hypertension.
2.
Hereditary spherocytosis.
3.
Thalassemia.
4.
Chronic lymphatic leukemia (CLL ).
5.
Amyloidosis.
6.
T.B, sarcoidosis.
7.
Metastatic carcinoma or sarcoma.
(N.B) massive splenomegaly when spleen size more than 1000gm.
- Mild splenomegaly (<500 gm)
1.
Acute splenitis.
2.
Acute splenic congestion.
3.
Infectious mononucleosis.
4.
Septicemia, SLE.
Disorders of thymus gland
I.
Thymic hyperplasia.
II.
Thymoma.
Thymic hyperplasia
There are two morphological forms of thymic hyperplasia”:
(1) True thymic hyperplasia: 
- It is characterized by an increase in the size and weight of thymus due to an increase in the number of thymic 
epithelial cells.
-More in children and young male patients. It is not associated with autoimmune diseases.
-(2) Lymphofollicular  hyperplasia:
- It is caused due to hyperplastic lymph follicles within the thymus.
-seen in myasthenia gravis.
The major treatment of massive thymic hyperplasia is surgical resection.
Thymoma
o Malignant epithelial tumor of the thymic gland. most commonly found in the 
prevascular mediastinum.
o It also can be found in the neck, pulmonary hilum, thyroid, lung, pleura, or 
pericardium..
o a  slowly growing tumor  and in the absence of metastasis, surgery is the treatment 
of choice.
o Complete resection and bland morphology are important prognostic features.
Malignant thymoma:: Classification accord

Summary :