Miscellaneous Bone Tumors 

1. Ewing Sarcoma & Primitive Neuroectodermal Tumor (PNET) are primary malignant small round-cell tumors of bone and soft tissue. They are viewed as the same tumor because they share an identical chromosome translocation; they differ only in degree of differentiation. PNETs demonstrate neural differentiation whereas Ewing sarcomas are undifferentiated. After osteosarcomas, they are the second most common pediatric bone sarcomas. Most patients are 10 to 15 years old. The common chromosomal abnormality is a translocation that causes fusion of the EWS gene with a member of the ETS family of transcription factors. The resulting hybrid protein functions as an active transcription factor to stimulate cell proliferation. These translocations are of diagnostic importance since almost all patients with Ewing tumor have t(11;22).

Pathological features

• Ewing sarcoma and PNETs arise in the medullary cavity but eventually invade the cortex and periosteum to produce a soft tissue mass.
• The tumor is tan-white, frequently with foci of hemorrhage and necrosis.

Microscopic features

• There are sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma.
• The cells have scant glycogen-rich cytoplasm.
• The presence of Homer-Wright rosettes (tumor cells circled about a central fibrillary space) indicates neural differentiation, and hence indicates by definition PNET. 

Ewing sarcoma and PNETs typically present as painful enlarging masses in the diaphyses of long tubular bones (especially the femur) and the pelvic flat bones. The tumor may be confused with osteomyelitis because of its association with systemic signs & symptoms of infection. X-rays show a destructive lytic tumor with infiltrative margins and extension into surrounding soft tissues. There is a characteristic periosteal reaction depositing bone in an onionskin fashion. 

2. Giant-Cell Tumor of Bone (GCT) is dominated by multinucleated osteoclast-type giant cells, hence the synonym osteoclastoma. GCT is benign but locally aggressive, usually arising in individuals in their 20s to 40s. Current opinion suggests that the giant cell component is likely a reactive macrophage population and the mononuclear cells are neoplastic. Tumors are large and red-brown with frequent cystic degeneration. They are composed of uniform oval mononuclear cells with frequent mitoses, with scattered osteoclast-type giant cells that may contain 30 or more nuclei.

The majority of GCTs arise in the epiphysis of long bones around the knee (distal femur and proximal tibia).
Radiographically, GCTs are large, purely lytic, and eccentric; the overlying cortex is frequently destroyed, producing a bulging soft tissue mass with a thin shell of reactive bone. Although GCTs are benign, roughly 50% recur after simple curettage; some malignant examples (5%) metastasize to the lungs 

Hypopituitarism

Hypopituitarism is caused by

1. Loss of the anterior pituitary parenchyma
    a. congenital 
    b. acquired  
    
2. Disorders of the hypothalamus e.g. tumors; these interfere with the delivery of pituitary hormone-releasing factors from the hypothalamus.  

Most cases of anterior pituitary hypofunction are caused by the following:
1. Nonfunctioning pituitary adenomas 
2. Ischemic necrosis of the anterior pituitary is an important cause of pituitary insufficiency. This requires destruction of 75% of the anterior pituitary. 

Causes include  

a. Sheehan syndrome, refers to postpartum necrosis of the anterior pituitary, and is the most cause. During pregnancy the anterior pituitary enlarges considerably because of an increase in the size and number of prolactin-secreting cells. However, this physiologic enlargement of the gland is not accompanied by an increase in blood supply. The enlarged gland is therefore vulnerable to ischemic injury, especially in women who develop significant hemorrhage and hypotension during the peripartum period. The posterior pituitary is usually not affected. 

b. Disseminated intravascular coagulation 
c. Sickle cell anemia 
d. Elevated intracranial pressure 
e. Traumatic injury
f. Shock states

3. Iatrogenic i.e.  surgical removal or radiation-induced destruction
4. Inflammatory lesions such as sarcoidosis or tuberculosis
5. Metastatic neoplasms involving the pituitary. 
6. Mutations affecting the pituitary transcription factor Pit-1 

Children can develop growth failure (pituitary dwarfism) as a result of growth hormone deficiency.

Gonadotropin or gonadotropin-releasing hormone (GnRH) deficiency leads to amenorrhea and infertility in women and decreased libido, impotence, and loss of pubic and axillary hair in men. TSH and ACTH deficiencies result in symptoms of hypothyroidism and hypoadrenalism. Prolactin deficiency results in failure of postpartum lactation. 

Nonspecific or Innate Immunity

1. Genetic factors

• Species: Guinea pig is very susceptible to tuberculosis.
• Race: Negroes are more susceptible to tuberculosis than whites
• Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.

2. Age Extremes of age are more susceptible.

3. Hormonal status. Low resistance in:

• Diabetes Mellitus.
• Increased corticosteroid levels.
• Hypothyroidism

4. Phagocytosis. Infections can Occur in :

• Qualitative  or quantitative defects in neutrophils and monocytes.
• Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
• Overload blockade of RES.

5. Humoral factors

• Lysozyme.
• Opsonins.
• Complement
• Interferon (antiviral agent secreted by cells infected by virus)

Nephrosclerosis
 Disease of the renal arteries.

 Clinical manifestations:
 (1) Benign (arterial) nephrosclerosis →  Caused by the formation of atherosclerotic plaques in the renal artery. Results in narrowing of the arterioles.

(2) Malignant nephrosclerosis → Caused by malignant hypertension. Common signs of malignant hypertension include severe hypertension, retinal hemorrhages, and hypertrophy of the left ventricle. Results in inflammatory changes in the vascular walls, which may lead to rupture of the glomerular capillaries.