Neuroblastoma and Related Neoplasms
Neuroblastoma is the second most common solid malignancy of childhood after brain tumors, accounting for up to10% of all pediatric neoplasms. They are most common during the first 5 years of life. Neuroblastomas may occur anywhere along the sympathetic nervous system and occasionally within the brain. Most neuroblastomas are sporadic. Spontaneous regression and spontaneous- or therapy-induced maturation are their unique features.  

Gross features
- The adrenal medulla is the commonest site of neuroblastomas. The remainder occur along the sympathetic chain, mostly in the paravertebral region of the abdomen and posterior mediastinum. 
- They range in size from minute nodules to large masses weighing more than 1 kg. 
- Some tumors are delineated by a fibrous pseudo-capsule, but others invade surrounding structures, including the kidneys, renal vein, vena cava, and the aorta. 
- Sectioning shows soft, gray-tan, brain-like tissue. Areas of necrosis, cystic softening, and hemorrhage may be present in large tumors. 

Microscopic features
- Neuroblastomas are composed of small, primitive-appearing neuroblasts with dark nuclei & scant cytoplasm, g rowing in solid sheets.  
- The background consists of light pinkish fibrillary material corresponding to neuritic processes of the primitive cells. 
- Typically, rosettes can be found in which the tumor cells are concentrically arranged about a central space filled with the fibrillary neurites.
- Supporting features include include immunochemical detection of neuron-specific enolase and ultrastructural demonstration of small, membrane-bound, cytoplasmic catecholamine-containing secretory granules.
- Some neoplasms show signs of maturation, either spontaneous or therapy-induced. Larger ganglion-like cells having more abundant cytoplasm with large vesicular nuclei and prominent nucleoli may be found in tumors admixed with primitive neuroblasts (ganglioneuroblastoma). Further maturation leads to tumors containing many mature ganglion-like cells in the absence of residual neuroblasts (ganglioneuroma). 

Many factors influence prognosis, but the most important are the stage of the tumor and the age of the patient. Children below 1 year of age have a much more favorable outlook than do older children at a comparable stage of disease. 

Miscroscopic features are also an independent prognostic factor; evidence of gangliocytic differentiation is indicative of a "favorable" histology. Amplification of the MYCN oncogene in neuroblastomas is a molecular event that has profound impact on prognosis. The greater the number of copies, the worse is the prognosis. MYCN amplification is currently the most important genetic abnormality used in risk stratification of neuroblastic tumors. 

About 90% of neuroblastomas produce catecholamines (as pheochromocytomas), which are an important diagnostic feature (i.e., elevated blood levels of catecholamines and elevated urine levels of catecholamine metabolites such as vanillylmandelic acid [VMA] and homovanillic acid [HVA]). 

Acute pericarditis

1. Characterized by inflammation of the pericardium.
2. Causes include:
a. Viral infection.
b. Bacterial infection, including Staphylococcus, Pneumococcus.
c. Tuberculosis.
d. MI.
e. Systemic lupus erythematosus.
f. Rheumatic fever.

3. Signs and symptoms include:
a. Pericardial friction rub on cardiac auscultation.
b. Angina.
c. Fever.

4. Consequences include constrictive pericarditis,which results from fusion and scarring of the pericardium. This may lead to the restriction of ventricular expansion, preventing the heart chambers from filling normally.

Streptococcal pharyngitis:

A disease of young people, enlarged lymphoid nodules and keratin plugs in the tonsillar pits is seen Complications include retro-pharyngeal abscess (quinsy)

Cellulitis of the deep tissues of the neck is Ludwig's angina

Scarlet fever ("scarlatina") is a strep throat caused by a streptococcus with the gene to make one of the erythrogenic toxins, Patients have a rash with PMNs

Streptococcal skin infections (Impetigo)

Erysipelas is a severe skin infection caused by group A strep; geographic of red, thickened, indurated areas of the skin are characteristic. Unlike staph infections, there is usually little or no tissue necrosis

Post-streptococcal hypersensitivity diseases include rheumatic fever, post-streptococcal glomerulonephritis, and some cases of erythema nodosum

Acne vulgaris is a chronic inflammatory disorder usually present in the late teenage years characterized by comedones, papules, nodules, and cysts.
 - subdivided into obstructive type with closed comedones (whiteheads) and open comedones (blackheads) and the inflammatory type consisting of papules, pustules, nodules, cysts and scars.
 - pathogenesis of inflammatory acne relates to blockage of the hair follicle with keratin and sebaceous secretions, which are acted upon by Propionibacterium acnes (anaerobe) that causes the release of irritating fatty acids resulting in an inflammatory response.
 - pathogenesis of the obstructive type (comedones) is related to plugging of the outlet of a hair follicle by keratin debris.
 - chocolate, shellfish, nuts iodized salt do not aggravate acne.
 - obstructive type is best treated with benzoyl peroxide and triretnoin (vitamin A acid)
 - treatment of inflammatory type is the above plus antibiotics (topical and/or systemic; erythromycin, tetracycline, clindamycin).

Amyotrophic lateral sclerosis (Lou Gehrig’s disease)
a. Characterized by the rapid degeneration of motor neurons in the spinal cord and corticospinal tracts.
b. More common in men in their 50s.
c. Clinically, the disease results in rapidly progressive muscle atrophy due to denervation. Other symptoms include fasciculations, hyperreflexia, spasticity, and pathologic reflexes. Death usually occurs within a few years from onset, usually by respiratory failure or infection.

Autoimmune Diseases
These are a group of disease where antibodies  (or CMI) are produced against self antigens, causing disease process.

Normally one's immune competent cells do not react against one's own tissues.
This is due to self tolerance acquired during embryogenesis. Any antigen encountered at
that stage is recognized as self and the clone of cells capable of forming the corresponding antibody is suppressed.

Mechanism of autoimmunity

(1) Alteration of antigen

 -Physicochemical denaturation by UV light, drugs etc. e.g. SLE.
- Native protein may turn antigenic  when a foreign hapten combines with it, e.g. Haemolytic anemia with Alpha methyl dopa.

(2) Cross reaction: Antibody produced against foreign antigen may cross react with native protein because of partial similarity e.g. Rheumatic fever.

(3) Exposure of sequestered antigens: Antigens not normally exposed to immune competent cells are not accepted as self as tolerance has not been developed to them. e.g. thyroglobulin, lens protein, sperms.

(4) Breakdown of tolerance : 
- Emergence of forbidden clones (due to neoplasia of immune system as in lymphomas and lymphocytic leukaemia)
- Loss of suppressor T cells as in old age and CMI defects

Autoimmunity may be
- Organ specific.
-  Non organ specific (multisystemic)

I. Organ specific.
(I) Hemolytic anaemia:
- Warm or cold antibodies (active at 37° C or at colder temperature)
- They may lyse the RBC by complement activation or coat them and make them vulnerable to phagocytosis

(ii) Hashimoto's thyroiditis:
 
- Antibodies to thyroglobulin and microsomal antigens.
- Cell mediated immunity.
- Leads to chronic. destructive thyroiditis.

(3) Pernicious anemia

Antibodies to gastric parietal cells and to intrinsic factor.

2. Non organ specific.

Lesions are seen in more than one system but principally affect blood vessels and connective tissue (collagen diseases).

(I) Systemic lupus erythematosus  (SLE). Antibodies to varied antigens are seen. Hence it is possible that there is abnormal reactivity of the immune system in self recognition.

Antibodies have been demonstrated against:

- Nuclear material (antinuclear I antibodies) including DNA. nucleoprotein etc. Anti nuclear antibodies are demonstrated by LE cell test.
- Cytoplasmic organelles- mitochondria, rib osomes, Iysosomes.
- Blood constituents like RBC, WBC. platelets, coagulation factors.

Mechanism. Immune complexes of body proteins and auto antibodies deposit in various organs and cause damage as in type III hypersensitivity

Organs involved
- Skin- basal dissolution and collagen degeneration with fibrinoid vasculitis.
- Heart- pancarditis.
- Kidneys- glomerulonephritis of focal, diffuse or membranous type 
- Joints- arthritis. 
- Spleen- perisplenitis and vascular thickening (onion skin).
- Lymph nodes- focal necrosis and follicular hyperplasia.
- Vasculitis in other organs like liver, central or peripheral nervous system etc,

2. Polyarteritis nodosa. Remittant .disseminated necrotising vasculitis of small and medium sized arteries

Mechanism :- Not definitely known. Proposed immune reaction to exogenous or auto antigens 

Lesion : Focal panarteritis- a segment of vessel is involved. There is fibrinoid necrosis with initially acute and later chronic inflammatory cells. This may result in haemorrhage and aneurysm.

Organs involved. No organ or tissue is exempt but commonly involved organs are :
- Kidneys.
- Heart.
- Spleen.
- GIT.

3. Rheumatoid arthritis. A disease primarily of females in young adult life. 

Antibodies

- Rheumatoid factor (An IgM antibody to self IgG)
- Antinuclear antibodies in 20% patients.

Lesions

- Arthritis which may progress on to a crippling deformity.
- Arteritis in various organs- heart, GIT, muscles.
- Pleuritis and fibrosing alveolitis.
- Amyloidosis is an important complication.

4. Sjogren's  Syndrome. This is constituted by 
- Kerato conjunctivitis sicca
- Xerostomia
- Rheumatoid arthritis. 

Antibodies

- Rheumatoid factor

- Antinuclear factors (70%).
- Other antibodies like antithyroid, complement fixing Ab etc
- Functional defects in lymphocytes. There is a higher incidence of lymphoma

5. Scleroderma (Progressive systemic sclerosis)
Inflammation and progressive sclerosis of connective tissue of skin and viscera.

Antibodies
- Antinuclear antibodies.
- Rheumatoid factor. .
- Defect is cell mediated.

lesions

- Skin- depigmentation, sclerotic atrophy followed by cakinosis-claw fingers and mask face.
- Joints-synovitis with fibrosis
- Muscles- myositis.
- GIT- diffuse fibrous replacement of muscularis resulting in hypomotility and malabsorption
- Kidneys changes as in SLE and necrotising vasculitis.
- Lungs – fibrosing alveolitis.
- Vasculitis in any organ or tissue.

6.Wegener’s granulomatosis. A complex of:

- Necrotising lesions in upper respiratory tract.
- Disseminated necrotising vasculitis.
- Focal or diffuse glomerulitis.

Mechanism. Not known. It is classed with  autoimmune diseases because of the vasculitis  resembling other immune based disorders.