NEOPLASIA

 An abnormal. growth, in excess of and uncoordinated with normal tissues Which persists in the same excessive manner after cessation of the stimuli which evoked the change.

Tumours are broadly divided by their behaviors into 2 main groups, benign and malignant.

Through most tumours can be classified in the benign or malignant category . Some exhibits an intermediate behaviours.

CLASSIFICATION

Some tumours can not be clearly categorized in the above table e.g.

• Mixed tumours like fibroadenoma of the breast which is a neoplastic proliferation of both epithelial and mesenchmal tissues.
• Teratomas which are tumours from germ cells (in the glands) and totipotent cells

(in extra gonodal sites like mediastinun, retroperitoneum and presacral region). These are composed of multiple tissues indicative of differentiation into the derivatives of the three germinal layers.

• Hamartomas which are malformations consisting of a haphazard mass of  tissue normally present at that site.

Congestive heart failure (CHF)
A. Left-sided CHF

1. May result from nearly any heart disease affecting the left ventricle (e.g., ischemic heart disease, hypertension, valvular disease).
2. Common signs and symptoms include:
a. Dyspnea (shortness of breath) exacerbated by exertion.
b. Paroxysmal nocturnal dyspnea.
c. Orthopnea.
d. Tachypnea.
e. Pleural effusion.
f. Consequences include pulmonary edema.

B. Right-sided CHF

1. The most common cause of right heart failure is left heart failure. It uncommonly occurs in isolation. Other causes include left-sided lesions (mitral stenosis), pulmonary hypertension, cardiomyopathy, and tricuspid or pulmonary valvular disease.
2. Frequently presents with peripheral edema, especially in the ankles and feet (i.e., dependent edema), enlarged liver or spleen, and distention of the neck veins.

Haemolytic anaemia 

Anemia due to increased red cell destruction (shortened life span)

Causes:

A. Corpuscular defects:

1.Membrane defects:

    - Spherocytosis.
    - Elliptocytosis.

2. Haemoglobinopathies:

    - Sickle cell anaemia.
    - Thalassaemia
    - Hb-C, HBD, HbE.
    
3. Enzyme defects .deficiency of:

    - GIucose -6 phosphate dehydrogenase (G6-PD)
    - Pyruvate kinase
    
4. Paroxysmal nocturnal haemoglobinuria.

B. Extracorpusular mechanisms 

1. Immune based:
    - Autoimmune haemolytic anaemia.
    - Haemolytic disease of new born.
    - Incompatible transfusion.
    - Drug induced haemolysis
    
2. Mechanical haemolytic anaemia.
3. Miscellaneous due to :

    - Drugs and chemicals.
    - Infections.
    - Burns.

features of haemolytic anaemia

- Evidence of increased Hb breakdown:

    -> Unconjugated hyperbilirubinaemia.
    -> Decreased plasma haptoglobin.
    -> Increased urobilinogen and stercobilinogen.
    -> Haemoglobinaemia, haemoglobinuria and haemosiderinuria if Intravascular haemolysis occurs.

- Evidence or compensatory erythroid hyperplasia:

    -> Reticulocytosis and nucleated RBC in peripheral smear.
    -> Polychromasia and macrocytes 
    -> Marrow erythroid hyperplasia
    -> Skull and other bone changes.

- Evidences of damage to RBC:

    -> Spherocytes and increased osmotic fragility
    -> Shortened life span.
    -> Fragmented RBC.
    -> Heinz bodies.
 

Cushing’s syndrome

The symptoms and signs of Cushing’s syndrome are associated with prolonged inappropriate elevation of free corticosteroid levels.

Clinical features

- Central obesity and moon face.
- Plethora and acne.
- Menstrual irregularity.
- Hirsutism and hair thinning.
- Hypertension.
- Diabetes.
- Osteoporosis—may cause collapse of vertebrae, rib fractures.
- Muscle wasting and weakness.
- Atrophy of skin and dermis—paper thin skin with bruising tendency, purple striae.

Aetiopathogenesis — patients with Cushing’s syndrome can be classified into two groups on the basis of whether the aetiology of the condition is ACTH dependent or independent. 

Classification of Cushing's syndrome

ACTH dependent- Iatrogenic (ACTH therapy) Pituitary hypersecretion of ACTH Ectopic ACTH syndrome (benign or malignant non-endocrine tumour)

Non-ACTH dependent - Iatrogenic, e.g. prednisolone Adrenal cortical adenoma , Adrenal cortical carcinoma

ACTH-dependent aetiology:

- Pituitary hypersecretion of ACTH (Cushing’s disease)—bilateral adrenal hyperplasia secondary to excessive secretion of ACTH by a corticotroph adenoma of the pituitary gland.
- Production of ectopic ACTH or corticotrophin- releasing hormone (CRH) by non-endocrine neoplasm, e.g. small cell lung cancer and some carcinoid tumours. In cases of malignant bronchial tumour, the patient rarely survives long enough to develop any physical features of Cushing’s syndrome.

Non-ACTH-dependent aetiology

Iatrogenic steroid therapy—most common cause of Cushing’s syndrome.
Adrenal cortical adenoma—well-circumscribed yellow tumour usually 2–5 cm in diameter.
Extremely common as an incidental finding in up to 30% of all post-mortem examinations. The yellow colour is due to stored lipid (mainly cholesterol) from which the hormones are synthesised. The vast majority have no clinical effects (i.e. they are non-functioning adenomas), with only a small percentage producing Cushing’s syndrome.

Adrenal cortical carcinoma—rare and almost always associated with the overproduction of hormones, usually glucocorticoids and sex steroids. 

Cushing’s syndrome mixed with androgenic effects which are particularly noticeable in women. Tumours are usually large and yellowish white in colour. Local invasion and metastatic spread are common.

Irrespective of the aetiology, the diagnosis is based on clinical features and the demonstration of a raised plasma cortisol level.
The aetiology of the disorder is elucidated through:
- Raised urinary cortisol in the first instance, but further testing is required.
- Low-dose dexamethasone suppression test (suppression of cortisol levels in Cushing’s disease due to suppression of pituitary ACTH secretion, but a lack of suppression suggests ACTH-independent Cushing’s syndrome).
- MRI and CT scan visualisation of pituitary and adrenal glands.
- Analysis of blood ACTH (high = pituitary adenoma or ectopic ACTH source; low = primary adrenal tumour due to feedback suppression).
- Treatment of the underlying cause is essential as untreated Cushing’s syndrome has a 50% 5-year mortality rate.

The therapeutic administration of glucocorticosteroids (e.g. prednisolone) is a common cause of the features of Cushing’s syndrome. 

Nevus

A nevus refers to any congenital lesion of the skin, while a nevocellular nevus specifically refers to a benign tumor of neural crest-derived cells that include modified melanocytes of various shapes (nevus cells).
 - nevocellular nevi are generally tan to deep brown, uniformly pigmented, small papules with well-defined, rounded borders.
 - most nevocellular nevi are subdivided into junctional, intradermal, or compound types.
 - most nevocellular nevi begin as junctional nevi with nevus cells located along the basal cell layer producing small, flat lesions, which are only slightly raised. 
- junctional nevi usually develop into compound nevi as nevus cells extend into the underlying superficial dermis forming cords and columns of cells (compound: nevi at junction and in the dermis).
 - eventually, the junctional component of a nevocellular nevus is lost, leaving only nevus cells within the dermis, thus the term intradermal nevus.
 - junctional → compound → intradermal nevus.
 - although uncommon, certain nevi may evolve into a malignant melanoma, particularly those which are congenital and those which are referred to as dysplastic nevi.
 - a dysplastic nevus is commonly associated with patients who have multiple scattered nevi over the entire body (dysplastic nevus syndrome) with individual lesions that have a diameter greater than 1 cm.

Cholelithiasis (Biliary calculi)
- These are insoluble material found within the biliary tract and are formed of bile constituents (cholesterol, bile pigments and calcium salts). 

Sites: - -Gall bladder, extra hepatic biliary tract.  Rarely, intrahepatic biliary tract. 

Predisposing factors:- 
- Change in the composition of bile. - It is the disturbance of the ratio between cholesterol and lecithin or bile salts which may be due to Hypercholesterolaemia which may be hereditary or the 4 F (Female, Forty, Fatty, Fertile). Drugs as clofibrate and exogenous estrogen. High intake of calories (obesity).
Increased concentration of bilirubin in bile- pigment stones
Hypercalcaemia:- Calcium carbonate stones.

2- Staisis.
3- Infection. 

Pathogenesis   i- Nucleation or initiation of stone formation:- The nidus may be cholesterol “due to supersaturation” Bacteria, parasite
RBCs or mucous.  
ii- Acceleration:- When the stone remains in the gall bladder, other constituents are added to the
nidus to form the stone. 

Complications of gall stones:- 
- Predispose to infection.- Chronic irritation leading to 
a. Ulceration       b. Squamous metaplasia & carcinoma.