Cartilage-Forming Tumors

1. Osteochondroma (Exostosis) is a relatively common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood (male-to-female ratio of 3:1); multiple osteochondromas become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder. Inactivation of both copies of the EXT gene (a tumor suppressor gne) in chondrocytes is implicated in both sporadic and hereditary osteochondromas. Osteochondromas develop only in bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones, especially about the knee. They tend to stop growing once the normal growth of the skeleton is completed. Occasionally they develop from flat bones (pelvis, scapula, and ribs). Rarely, exostoses involve the short tubular bones of hands and feet.

Pathological features

• Osteochondromas vary from 1-20cm in size.
• The cap is benign hyaline cartilage. 
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with cortex of the host bone.
Osteochondromas are slow-growing masses that may be painful. Osteochondromas rarely progress to chondrosarcoma or other sarcoma, although patients with the multiple hereditary exostoses are at increased risk of malignant transformation. 

2. Chondroma 

It is a benign tumor of hyaline cartilage. When it arises within the medullary cavity, it is termed enchondroma; when on the bone surface it is called juxtacortical chondroma. Enchondromas are usually diagnosed in persons between ages 20 and 50 years; they are typically solitary and located in the metaphyseal region of tubular bones, the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas preferentially involving one side of the body. Chondromas probably develop from slowly proliferating rests of growth plate cartilage.

Pathological features 

• Enchondromas are gray-blue, translucent nodules usually smaller than 3 cm.
• Microscopically, there is well-circumscribed hyaline matrix and cytologically benign chondrocytes.
Most enchondromas are detected as incidental findings; occasionally they are painful or cause pathologic fractures. Solitary chondromas rarely undergo malignant transformation, but those associated with enchondromatosis are at increased risk. 

3. Chondrosarcomas are malignant tumors of cartilage forming tissues. They are divided into conventional chondrosarcomas and chondrosarcoma variants. Each of these categories comprises several distinct types, some defined on microscopic grounds & others on the basis of location within the affected bone, for e.g. they are divided into central (medullary), peripheral (cortical), and juxtacortical (periosteal). The common denominator of chondrosarcoma is the production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells (cf osteosarcoma). Chondrosarcomas occur roughly half as frequently as osteosarcomas; most patients age 40 years or more, with men affected twice as frequently as women 

Pathological features 
Conventional chondrosarcomas arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex. They exhibit malignant hyaline or myxoid stroma. Spotty calcifications are typically present. The tumor grows with broad pushing fronts into marrow spaces and the surrounding soft tissue. Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity. Low-grade tumors resemble normal cartilage. Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes. Dedifferentiated chondrosarcomas refers to the presence of a poorly differentiated sarcomatous component at the periphery of an otherwise typical low-grade chondrosarcoma. Other histologic variants include myxoid, clear-cell and mesenchymal chondrosarcomas. Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs. A slowly growing lowgrade tumor causes reactive thickening of the cortex, whereas a more aggressive high-grade neoplasm destroys the cortex and forms a soft tissue mass. There is also a direct correlation between grade and biologic behavior. 
Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors. High-grade Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.

Growth and spread of tumours

Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.

Modes of spread of malignant tumours

- local, invasion. This is a feature of all malignant tumors and  takes place along tissue spaces and facial planes
    o    Lymphatic spread. Most often seen in carcinomas. This can be in the form of 
    o    Lymphatic permeation:  Where the cells extend along the lymphatics as a  solid core 
    o    Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode

-Vascular spread :  This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.

Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.

Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.

-Body cavities and natural passages
    o    Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
 

CARCINOMA IN SITU

Epithelial malignancy which has not yet invaded even -the local confines viz basement membrane is termed as carcinoma in situ (intra epithelial neoplasia, pre-invasive cancer)

This lesion merges morphologically with severe dysplasia

Common sites for carcinoma-in-situ :

• Cervical squamous epithelium
• Oropharynx
• Bronchial epithelium.
• Breast ducts and lobules.
• Skin, in the form of Bowen's disease.
• Glans penis and vulva in the form of Erythroplasia of Queyrat

Pneumoconioses—are environmentally related lung diseases that result from chronic inhalation of various substances.

1. Silicosis (stone mason’s disease) 
a. Inhalant: silica dust.
b. Associated with extensive fibrosis of the lungs.
c. Patients have a higher susceptibility to tuberculosis infections.

2. Asbestosis
a. Inhalant: asbestos fibers.
b. Associated with the presence of pleural plaques.
c. Consequences include:
(1) Mesothelioma (malignant mesothelial tumor).
(2) Bronchogenic carcinoma.

3. Anthracosis
a. Inhalant: carbon dust.
b. Usually not as harmful as silicosis or asbestosis.
c. Associated with the presence of macrophages containing carbon.

Cardiac arrhythmia

Cardiac arrhythmia is a group of conditions in which muscle contraction of the heart is irregular for any reason.

Tachycardia :A rhythm of the heart at a rate of more than 100 beats/minute , palpitation present
Causes : stress, caffeine, alcohol, hyperthyroidism or drugs

Bradycardia : slow rhythm of the heart at a rate less than 60 beats/min 

Atrial Arrhythmias 

- Atrial fibrillation

Atrial Dysrhythmias 

- Premature atrial contraction
- Atrial flutter
- Supraventricular tachycardia
- Sick sinus syndrome

Ventricular Arrhythmias 

- Ventricular fibrillation

Ventricular Dysrhythmias 

- Premature ventricular contraction
- Pulseless electrical activity
- Ventricular tachycardia
- Asystole

Heart Blocks 

- First degree heart block
- Second degree heart block 
o    Type 1 Second degree heart block a.k.a. Mobitz I or Wenckebach
o    Type 2 Second degree heart block a.k.a. Mobitz II
- Third degree heart block a.k.a. complete heart block

Atrial fibrillation

Atrial fibrillation  is a cardiac arrhythmia (an abnormality of heart rate or rhythm) originating in the atria.
AF is the most common cardiac arrhythmia

Signs and symptoms

Rapid and irregular heart rates
palpitations, exercise intolerance, and occasionally produce angina and congestive symptoms of shortness of breath or edema
Paroxysmal atrial fibrillation is the episodic occurence of the arrhythmia  Episodes may occur with sleep or with exercise

Diagnosis: 

Electrocardiogram
- absence of P waves
- unorganized electrical activity in their place
- irregularity of R-R interval due to irregular conduction of impulses to the ventricles

Causes:

- Arterial hypertension
- Mitral valve disease (e.g. due to rheumatic heart disease or mitral valve prolapse)
- Heart surgery
- Coronary heart disease
- Excessive alcohol consumption ("binge drinking" or "holiday heart")
- Hyperthyroidism
- Hyperstimulation of the vagus nerve, usually by having large meals

Treatment

Rate control by 
Beta blockers (e.g. metoprolol)
Digoxin
Calcium channel blockers (e.g. verapamil)

Rhythm control

Electrical cardioverion by application of a DC electrical shock
Chemical cardioversion is performed with drugs eg amiodarone

Radiofrequency ablation : uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue It is used in recurrent AF

In confirmed AF, anticoagulant treatment is a crucial way to prevent stroke

Atrial flutter

Atrial flutter is a regular, rhythmic tachycardia originating in the atria. The rate in the atria is over 220 beats/minute, and typically about 300 beats/minute

he morphology on the surface EKG is typically a sawtooth pattern.

The ventricles do not beat as fast as the atria in atrial flutter

Supraventricular tachycardia

apid rhythm of the heart in which the origin of the electrical signal is either the atria or the AV node
it is important to determine whether a wide-complex tachycardia is an SVT or a ventricular tachycardia, since they are treated differently

Sick sinus syndrome : a group of abnormal heartbeats (arrhythmias) presumably caused by a malfunction of the sinus node, the heart's "natural" pacemaker.

Ventricular fibrillation

is a cardiac condition which consists of a lack of coordination of the contraction of the muscle tissue of the large chambers of the heart. The ventricular muscle twitches randomly, rather than contracting in unison, and so the ventricles fail to pump blood into the arteries and into systemic circulation.

Ventricular fibrillation is a medical emergency: if the arrhythmia continues for more than a few seconds, blood circulation will cease, as evidenced by lack of pulse, blood pressure and respiration, and death will occur. Ventricular fibrillation is a cause of cardiac arrest and sudden cardiac death
 

Osteopetrosis (Albers-Schönberg disease or marble bone disease) 

is a group of rare genetic disorders characterized by reduced osteoclast-mediated bone resorption and therefore defective bone remodelling. The bones are solid and heavy with no medullary canal, long ends are bulbous, small neural foramina compress nerves. The affected bone is grossly dense but fractures occur readily like a piece of chalk. 

Patients frequently have cranial nerve compressions by the surrouding bone, and recurrent infections. The latter is attributable to diminished hematopoiesis resulting from reduced marrow space with impressive hepatosplenomegaly due to extramedullary hematopoiesis 
 
a. Caused by abnormal osteoclasts. This results in defective bone remodeling (i.e., abnormally low bone resorption) and increased bone density, which may invade into bone marrow space.
b. Causes severe defects in infants, including:
(1) Anemia and infections—caused by decreased bone marrow.
(2) Blindness, deafness, paralysis of facial muscles—caused by the narrowing of cranial nerve foramina.
(3) Is life-threatening.
(4) Oral findings include delayed eruption of teeth.
c. Disease is less severe in adults