Bone-Forming Tumors

1. Osteoma is a benign lesion of bone that in many cases represent a developmental abnormaly or reactive growth rather than true neoplasms. They are most common in the head, including the paranasal sinuses. 
Microscopically, there is a mixture of woven and lamellar bone. They may cause local mechanical problems (e.g., obstruction of a sinus cavity) and cosmetic deformities. 

2. Osteoid Osteoma and Osteoblastoma 
are benign neoplasms with very similar histologic features. Both lesions typically arise during the 2nd & 3rd decades. They are well-circumscribed lesions, usually involving the cortex. The central area of the tumor, termed the nidus, is characteristically radiolucent. Osteoid osteomas arise most often in the proximal femur and tibia, and are by definition less than 2 cm, whereas osteoblastomas are larger. Localized pain is an almost universal complaint with osteoid osteomas, and is usually relieved by aspirin. Osteoblastomas arise most often in the vertebral column; they also cause pain, which is not responsive to aspirin. Malignant transformation is rare unless the lesion is treated with radiation. 

Gross features

• Both lesions are round-to-oval masses of hemorrhagic gritty tan tissue.
• A rim of sclerotic bone is present at the edge of both types of tumors. 

Microscopic features
• There are interlacing trabeculae of woven bone surrounded by osteoblasts.
• The intervening connective tissue is loose, vascular & contains variable numbers of giant cells.

3. Osteosarcoma

This is “a bone-producing malignant mesenchymal tumor.” Excluding myeloma and lymphoma, osteosarcoma is the most common primary malignant tumor of bone (20%). The peak age of incidence is 10-25 years with 75% of the affected patients are younger than age 20 years; there is a second peak that occurrs in the elderly, usually secondary to other conditions, e.g. Paget disease, bone infarcts, and prior irradiation. Most tumors arise in the metaphysis of the long bones of the extremities, with 60% occurring about the knee, 15% around the hip, & 10% at the shoulder. The most common type of osteosarcoma is primary, solitary, intramedullary, and poorly differentiated, producing a predominantly bony matrix.

Gross features

• The tumor is gritty, gray-white, often with foci of hemorrhage and cystic degeneration.
• It frequently destroys the surrounding cortex to extend into the soft tissue.
• There is extensive spread within the medullary canal, with replacement of the marrow. However, penetration
of the epiphyseal plate or the joint space is infrequent.

Microscopic features

• Tumor cells are pleomorphic with large hyperchromatic nuclei; bizarre tumor giant cells are common, as are mitoses.
• The direct production of mineralized or unmineralized bone (osteoid) by malignant cells is essential for diagnosis of osteosarcoma. The neoplastic bone is typically fine, lace-like but can also be deposited in broad sheets.
• Cartilage can be present in varying amounts. When malignant cartilage is abundant, the tumor is called a chondroblastic osteosarcoma.

Pathogenesis

• Several genetic mutations are closely associated with the development of osteosarcoma. In particular, RB gene mutations that occur in both sporadic tumors, and in individuals with hereditary retinoblastomas. In the latter there are germ-line mutations in the RB gene (inherited).
• Spontaneous osteosarcomas also frequently exhibit mutations in genes that regulate the cell cycle including p53, cyclins, etc.

Osteosarcomas typically present as painful enlarging masses.

Radiographs usually show a large, destructive, mixed lytic and blastic mass with infiltrating margins. The tumor frequently breaks the cortex and lifts the periosteum. The latter results in a reactive periosteal bone formation; a triangular shadow on x-ray between the cortex and raised periosteum (Codman triangle) is characteristic but not specific of osteosarcomas.
Osteosarcomas typically spread hematogenously; 10% to 20% of patients have demonstrable pulmonary metastases at the time of diagnosis. 

THROMBOPHLEBITIS AND  PHLEBOTHROMBOSIS 
- The deep leg veins account for more than 90% of cases (DVT) 
- the most important clinical predispositions are: congestive heart failure, neoplasia, pregnancy, obesity, the postoperative state, and prolonged bed rest or immobilization 
- local manifestations: distal edema, cyanosis, superficial vein dilation, heat, tenderness, redness, swelling, and pain 
- migratory thrombophlebitis (Trousseau sign): hypercoagulability occurs as a paraneoplastic syndrome related to tumor elaboration of procoagulant factors 

Thyroid goitres

A goitre is any enlargement of part or whole of the thyroid gland. There are two types:
1. Toxic goitre, i.e. goitre associated with thyrotoxicosis.
2. Non-toxic goitre, i.e. goitre associated with  normal or reduced levels of thyroid hormones.

Toxic goitre
Graves disease
This is the most common cause of toxic goitre 

Toxic multinodular goitre
This results from the development of hyperthyroidism in a multinodular goitre 

Non-toxic goitres
Diffuse non-toxic goitre (simple goitre)

This diffuse enlargement of the thyroid gland is classified into:

Endemic goitre—due to iodine deficiency. Endemic goiter occurs in geographic areas (typically mountainous)) where the soil, water, and food supply contain little iodine. The term endemic is used when goiters are present in more than 10% of the population in a given region. With increasing availability of dietary iodine supplementation, the frequency and severity of endemic goiter have declined significantly. Sporadic goiter is less common than endemic goiter. The condition is more common in females than in males, with a peak incidence in puberty or young adult life, when there is an
increased physiologic demand for T4.

Sporadic goitre—caused by goitrogenic agents (substances that induce goitre formation) or familial in origin. Examples of goitrogenic agents include certain cabbage species, because of their thiourea content, and specific drugs or chemicals, such as iodide, paraminosalicylic acid and drugs used in the treatment of thyrotoxicosis. Familial cases show inherited autosomal recessive traits, which interfere with hormone synthesis via various enzyme pathways (these are dyshormonogenic goitres). 
Hereditary enzymatic defects interfering with thyroid hormone synthesis (dyshormonogenetic goiter).

Physiological goitre—enlargement of the thyroid gland in females during puberty or pregnancy; the reason is unclear.

Multinodular goitre

This is the most common cause of thyroid enlargement and is seen particularly in the elderly (nearly all simple goitres eventually become multinodular). The exact aetiology is uncertain but it may represent an uneven responsiveness of various parts of the thyroid to fluctuating TSH levels over a period of many years.

Morphological features are:

• Irregular hyperplastic enlargement of the entire thyroid gland due to the development of wellcircumscribed nodules of varying size.
• Larger nodules filled with brown, gelatinous colloid; consequently, it is often termed multinodular colloid goitres.

Clinical features 

- A large neck mass, goiters may also cause airway obstruction, dysphagia, and compression of large vessels in the neck and upper thorax.
 - A hyperfunctioning ("toxic") nodule may develop within a long-standing goiter, resulting in hyperthyroidism. This condition is not accompanied by the infiltrative ophthalmopathy and dermopathy. 
 - Less commonly, there may be hypothyroidism.

Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus 

- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.

Adult Respiratory Distress Syndrome 
A constellation of pathologic and clinical findings initiated by diffuse injury to alveolar capillaries. This syndrome is associated with a multitude of clinical conditions which primarily damage the lung or secondarily as part of a systemic disorder. 

Pathogenesis 
There are many types of injuries which lead to the ultimate, common pathway, i.e., damage to the alveolar capillary unit. The initial injury most frequently affects the endothelium, less frequently the alveolar epithelium. Injury produces increased vascular permeability, edema, fibrin-exudation (hyaline membranes). Leukocytes (primarily neutrophils) plays a key role in endothelial damage. 

Pathology 
Heavy, red lungs showing congestion and edema. The alveoli contain fluid and are lined by hyaline membranes. 

Pathophysiology 
Severe respiratory insufficiency with dyspnea, cyanosis and hypoxemia refractory to oxygen therapy.

Cytopathologic techniques

Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.

Applications of cytopathology:

1. Screening for the early detection of asymptomatic cancer

2. Diagnosis of symptomatic cancer

3. Surveillance of patients treated for cancer

Cytopathologic methods

There are different cytopathologic methods including:

1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.

Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.

Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.

1. Exfoliative cytology

Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.

1. Abrasive cytology

Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.