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. 

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

Malignant Diseases of Skin
 
1. Bowen's disease refers to a carcinoma in situ on sun-exposed skin or on the vulva, glans a penis, or oral mucosa which has an association, in some cases, with a visceral malignancy.
2. Skin cancers associated with ultraviolet light damage include basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.
3. A basal cell carcinoma is the MC malignant tumor of the skin and occurs on sunexposed, hair-bearing surfaces.
 - Locally aggressive, infiltrating cancers arising from the basal cell layer of the epidermis and infiltrate the underlying superficial dermis.
 - they do not metastasize
 - BCC are commonly located on the face on the inner aspect of the nose, around the orbit and the upper lip where they appear as raised nodules containing a central crater with a pearly-colored skin surface and vascular channels.
 - microscopically, they have cords of basophilic staining cells originating from the basal cell layer infiltrating the dermis.
 - they commonly recur if they are not totally excised, because they are frequently multifocal. 
- the basal cell nevus syndrome is an autosomal-dominant disorder characterized by the development of basal cell carcinomas early in life with associated abnormalities of bone, skin, nervous system, eyes, and reproductive system. 

Acute leukaemia
Lympheblastic is commoner in children and myeloblastic in adults .

Features:
- Anaemia.
- Fever and infections especially oral and respiratory.
- Haemorrhagic tendencies.
- Bone pains and tenderness (sternal).
- Lymphnode enlargement especially in lymphocytic.
- Gum hypertrophy especially in monocytic.

Blood picture:

- Anaemia and thrombocytopenia.
- Leucocyte count usually 20,-50,000/cu.mm. It may be less in subleukaemic leukaemia (even leucopenic levels may be seen).
- Blast cells form 30-90% of cells. Smudge cells and basket cells are seen .The type of balst cell may be recognised  by the associated more mature forms or by special cytochemical stains
- Blasts may be few in peripheral blood in the aleukamic stage

 Bone Marrow

- May be a dry tap , necessitating a trephine biopsy 
- Hypercellular with 70-90% blasts
- Reduction in megakaryocytes and erythroid cells
 

HYPERTROPHY
Increase in the size of an organ or tissue due to increase in the size of its Constituent cells.

1. Skeletal muscle due to -exercise.

2. Cardiac muscle of:
- Left ventricle in:
    o    Hypertension.
    o    Aortic valvular lesion.
    o    Severe anaemia.
- Right ventricle in :
    o    Mitral stenosis
    o    Cor pulmonale
    
3. Smooth muscle of:

- GIT proximal to strictures.
- Uterus in pregnancy.
 

Lymphangitis 
is the acute inflammation due to bacterial  infections spread into the lymphatics most common are group A β-hemolytic streptococci. 
lymphatics are dilated and filled with an exudate of neutrophils and monocytes.  
red, painful subcutaneous streaks (the inflamed lymphatics), with painful enlargement of the draining lymph nodes (acute lymphadenitis).  
subsequent passage into the venous circulation can result in bacteremia or sepsis.