Immunohistochemistry

 This is a method is used to detect a specific antigen in the tissue in order to identify the type of disease.

Lichen planus is an itchy, violaceous, flat-topped papule highlighted by white dots or lines called Wickham's striae.
 - lichen planus may occur in the oral mucosa, where it has a fine white net-like appearance.
 - increased epidermal proliferation; ? immunologic; initiated by epidermal injury from drugs, viruses, or topical agents.
 - characteristic histologic features include:
 - hyperkeratosis
 - absence of parakeratosis
 - prominent stratum granulosum
 - an irregular "saw toothed" accentuation of the rete pegs. 

 - dermal-epidermal junction obscured by a band-like infiltrate of lymphocytes.
 - It is generally self-limiting and resolves spontaneously 1 to 2 years after onset; however, the oral lesions may persist for years.

Lymphomas

A. Hodgkin’s disease

1. Characterized by enlarged lymph nodes and the presence of Reed-Sternberg cells (multinucleated giant cells) in lymphoid tissues.

2. Disease spreads from lymph node to lymph node in a contiguous manner.

3. Enlarged cervical lymph nodes are most commonly the first lymphadenopathy observed.

4. The cause is unknown.

5. Occurs before age 30.

6. Prognosis of disease depends largely on the extent of lymph node spread and systemic involvement.

B. Non-Hodgkin’s lymphoma

1. Characterized by tumor formation in the lymph nodes.

2. Tumors do not spread in a contiguous manner.

3. Most often caused by the proliferation of abnormal B cells.

4. Occurs after age 40.

5. Example: Burkitt’s lymphoma

a. Commonly associated with an EpsteinBarr virus (EBV) infection and a genetic mutation resulting from the translocation of the C-myc gene from chromosome 8 to 14.

b. The African type occurs in African children and commonly affects the mandible or maxilla.

c. In the United States, it most commonly affects the abdomen.

d. Histologically, the tumor displays a  characteristic “starry-sky” appearance.

Cor pulmonale
a failure of the right side of the heart. It is caused by prolonged high blood pressure in the right ventricle of the heart, which in turn is most often caused by pulmonary hypertension - prolonged high blood pressure in the arteries or veins of the lungs. People with heart disease, or lung diseases such as cystic fibrosis, are at greater risk.

Pathophysiology

There are several mechanisms leading to pulmonary hypertension and cor pulmonale:
Pulmonary vasoconstriction
Anatomic changes in vascularisation
Increased blood viscosity
Primary pulmonary hypertension

Causes

Acute: 
•    Massive pulmonary embolization
•    Exacerbation of chronic cor pulmonale
Chronic: 
•    COPD
•    Loss of lung tissue following trauma or surgery
 

Diagnostic techniques used in pathology

The pathologist uses the following techniques to the diagnose diseases:

a. Histopathology

b. Cytopathology

c. Hematopathology

d. Immunohistochemistry

e. Microbiological examination

f. Biochemical examination

g. Cytogenetics

h. Molecular techniques

i. Autopsy

THROMBOSIS 
Pathogenesis (called Virchow's triad):
1. Endothelial* Injury ( Heart, Arteries)
2. Stasis
3. Blood Hypercoagulability

- Endothelial cells are special type of cells that cover the inside surface of blood vessels and heart.

CONTRIBUTION OF ENDOTHELIAL CELLS TO COAGULATION

Intact endothelial cells maintain liquid blood flow by: 

1- inhibiting platelet adherence
2- preventing coagulation factor activation
3- lysing blood clots that may form.

Endothelial cells can be stimulated by direct injury or by various cytokines that are produced during inflammation.

Endothelial injury results in:
1- expression of procoagulant proteins (tissue factor and vWF)→ local thrombus formation.
2- exposure of underlying vWF and basement membrane collagen  →  platelet aggregation and thrombus formation. 

RESPONSE OF VASCULAR WALL CELLS TO INJURY( PATHOLOGIC EFFECT OF VASCULAR HEALING) 

Injury to the vessel wall results in a healing response, involving:
- Intimal expansion (proliferating SMCs and newly synthesized ECM). This involves signals from ECs, platelets, and macrophages; and mediators derived from coagulation and complement cascades.

- luminal stenosis & blockage of vascular flow 

Causes of Endothelial injury
1. Valvulitis
2. MI
3. Atherosclerosis
4. Traumatic or inflammatory conditions
5. Increased Blood Pressure
6. Endotoxins
7. Hypercholesterolemia
8. Radiation
9. Smoking 

Stasis

- Stasis is a major factor in venous thrombi
- Normal blood flow is laminar (platelets flow centrally in the vessel lumen, separated from the endothelium by a slower moving clear zone of
plasma)
- Stasis and turbulence cause the followings:

Disuption of normal blood flow 
prevent dilution of activated clotting factor
retard inflow of clotting factor inhibitor
promote endothelial cell injury

Causes of Stasis
1. Atherosclerosis
2. Aneurysms
3. Myocardial Infarction ( Non-cotractile fibers)
4. Mitral valve stenosis (atrial dilation)
5. Hyper viscosity syndromes (PCV and Sickle Cell anemia)

Hypercoagulability
A. Genetic (primary):
- mutations in the factor V gene and the prothrombin gene are the most common
B. Acquired (secondary):
- multifactorial and more complicated 
- causes include: Immobilization, MI, AF, surgery, fracture, burns, Cancer, Prosthetic cardiac valves 

MORPHOLOGY OF THROMBI 

Can develop anywhere in the CVS (e.g., in cardiac chambers,  valves, arteries, veins, or capillaries).

Arterial or cardiac thrombi→ begin at sites of endothelial injury; and are usually superimposed on an atherosclerotic plaque. 

 Venous thrombi → occur at sites of stasis. Most commonly the veins of the lower extremities (90%)

 Thrombi are focally attached to the underlying vascular surface; arterial and venous thrombi both tend to propagate toward the heart.
→ The propagating portion of a thrombus is poorly attached → fragmentation and embolus formation

LINES OF ZAHN

Thrombi can have grossly (and microscopically) apparent laminations called lines of Zahn; these represent pale platelet and fibrin layers alternating with darker erythrocyte-rich layers. 

Such lines are significant in that they represent thrombosis of flowing blood. 

Mural thrombi = Thrombi occurring in heart chambers or in the aortic lumen.

Causes: -Abnormal myocardial contraction (e.g. arrhythmias, dilated cardiomyopathy, or MI) -endomyocardial injury (e.g. myocarditis, catheter trauma)

Vegetations ->Thrombi on heart valves 

1- Bacterial or fungal blood-borne infections - (infective endocarditis,). 

2- Non-bacterial thrombotic endocarditis occur on sterile valves.

Fate of thrombi 

1. Propagation → Thrombi accumulate additional platelets and fibrin, eventually causing vessel obstruction 

2. Embolization → Thrombi dislodge or fragment and are transported elsewhere in the vasculature 

3. Dissolution → Thrombi are removed by fibrinolytic activity (Usually in recent thrombi) 

4. Organization and recanalization → Thrombi induce inflammation and fibrosis. - recanalization (re-establishing some degree of flow) - Organization = ingrowth of endothelial cells, smooth cells and fibroblasts into the fibrin rich thrombus.

5. Superimposed infection (Mycotic aneurysm)

Venous thrombi → most common in veins of the legs 

a. Superficial: e.g. Saphenous veins. - can cause local congestion, swelling, pain, and tenderness along the course of the involved vein, but they rarely embolize

a. Deep: e.g. Popliteal, Femoral and iliac vein. - more serious because they may embolize - can occur with stasis or hypercoagulable states