THYROIDITIS 
The more common and clinically significant thyroidites are:  
1. Hashimoto thyroiditis 
2. Subacute granulomatous thyroiditis
3. Subacute lymphocytic thyroiditis 

Hashimoto thyroiditis 

Hashimoto thyroiditis (Chronic Lymphocytic Thyroiditis) is the most common cause of hypothyroidism. It results from gradual autoimmune destruction of the thyroid gland. There is striking female predominance (10: 1 to 20:1), and is most prevalent around a mean age of 50 years. 

Pathogenesis 
• The dominant feature is progressive destruction of thyroid follicular epithelial cells with gradual replacement by mononuclear cell infiltration and fibrosis. 
• Sensitization of CD4+ T-helper cells to thyroid antigens seems to be the initiating event.
• The reaction of CD4+ T cells with thyroid antigens produces interferon γ  which promote inflammation and activate macrophages. Injury to the thyroid results from the toxic products of these inflammatory cells. 
• CD8+ cytotoxic T cells also contribute to epithelial cells killing as are natural killer cells. 
• There is a significant genetic component to disease pathogenesis. This is supported by 
1.  The increased frequency of the disease in first-degree relatives, 
2.  Unaffected family members often have circulating thyroid autoantibodies.  

Gross features 
• The thyroid shows moderate, diffuse, and symmetric enlargement.
• The cut surface is pale, gray-tan, firm, nodular and somewhat friable. 
• Eventually there is thyroid atrophy 

Microscopic features

• There is widespread, diffuse infiltration of the parenchyma by small lymphocytes, plasma cells.  The lymphocytes are also form follicles some with well-developed germinal centers 
• The thyroid follicles are atrophic and lined by epithelial cells having abundant eosinophilic, granular cytoplasm (Hurthle cells). This is a metaplastic response to the ongoing injury; ultrastructurally the Hurthle cells are stuffed by numerous mitochondria. 
• Interstitial connective tissue is increased and may be abundant.

Hashimoto thyroiditis presents as painless symmetrical goiter, usually with some degree of hypothyroidism. In some cases there is an initial transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones ("hashitoxicosis"). As hypothyroidism supervenes T4 and T3 levels progressively fall & TSH levels are increased. Patients often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas. 

Subacute Granulomatous (de Quervain) Thyroiditis 

Subacute Granulomatous (de Quervain) Thyroiditis is much less common than Hashimoto disease.

- It is most common around the age of 40 years and occurs more frequently in women than in men.

- An upper respiratory infection just before the onset of thyroiditis. Thus, a viral infection is probably the cause.

- There is firm uni- or bilateral enlargement of the gland.

Microscopically, there is disruption of thyroid follicles, with extravasation of colloid. The extravasated colloid provokes a granulomatous reaction, with giant cells.
Thyroid function tests are those of thyrotoxicosis but with progression and gland destruction, a transient hypothyroid phase occurs. The condition is self-limited, with most patients returning to a euthyroid state within at most 2 months.

Subacute Lymphocytic Thyroiditis

Subacute Lymphocytic Thyroiditis may follow pregnancy (postpartum thyroiditis).

- It is most likely autoimmune in etiology, because circulating antithyroid antibodies are found in the majority of patients.

- It mostly affects middle-aged women and present as painless, mild, symmetric neck mass. Initially, there is thyrotoxicosis, followed by return to a euthyroid state within a few months. In a minority there is progression to hypothyroidism.

Microscopically, there is a lymphocytic infiltration and hyperplastic germinal center within the thyroid parenchyma; unlike Hashimoto thyroiditis, follicular atrophy or Hürthle cell metaplasia are not commonly seen.

Riedel thyroiditis 

Riedel thyroiditis is a rare disorder of unknown etiology, characterized by extensive fibrosis involving the thyroid and the surrounding neck structures. The presence of a hard and fixed thyroid mass may be confused clinically with thyroid cancer. It may be associated with idiopathic fibrosis in other sites, such as the retroperitoneum. The presence of circulating antithyroid antibodies in most patients suggests an autoimmune etiology. 

Growth and spread of tumours

Growth in excess of normal is a feature of all tumours but extension to tissue away from the site of origin is a feature of malignant tumours.

Modes of spread of malignant tumours

- local, invasion. This is a feature of all malignant tumors and  takes place along tissue spaces and facial planes
    o    Lymphatic spread. Most often seen in carcinomas. This can be in the form of 
    o    Lymphatic permeation:  Where the cells extend along the lymphatics as a  solid core 
    o    Lymphatic embolisation: Where a group of tumour cells break off and get carried to the draining mode

-Vascular spread :  This is a common and early mode of spread for sarcomas but certain carcinomas like renal cell carcinoma and chorio carcinoma have a predilection to early vascular spread.

Vascular spread is most often due .to invasion of venous channels and can be by permeation or embolisation.

Lungs, liver, bones and brain are the common sites for vascular metastasis but
different tumours have different organ preference for metastasis, e.g. : Bronchogenic carcinoma often spreads to liver and adrenals.

-Body cavities and natural passages
    o    Gastrointestinal carcinomas spread to ovaries (Krukenberg’s tomour)
 

Clinical genetics (cytogenetics),

This is a method in which inherited chromosomal abnormalities in the germ cells or acquired chromosomal abnormalities in somatic cells are investigated using the techniques of molecular biology.

Summary 
Hepatitis A → ssRNA → Picornavirus → Oral–anal
Hepatitis B → dsDNA → Hepadnavirus → Sexual contact , Blood (needles), Perinatal
Hepatitis C → ssRNA → Flavivirus → Sexual contact , Blood (needles)
Hepatitis D → ssRNA → Deltavirus → Sexual contact, Blood (needles)
Hepatitis E → ssRNA → Calicivirus → Oral–anal 

Cardiac tamponade
A. Caused by accumulation of fluid in the pericardium. This severe condition can quickly impair ventricular filling and rapidly lead to  decreased cardiac output and death.

1. Signs and symptoms include:
a. Hypotension.
b. Jugular venous distention.
c. Distant heart sounds.

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.