NEET MDS Lessons
General Pathology
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]).
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.
Agranulocytosis. Severe neutropenia with symptoms of infective lesions.
Drugs. are an important cause and the effect may be due to .
-Direct toxic effect.
-Hypersensitivity.
Some of the 'high risk drugs are.
-Amidopyrine.
-Antithyroid drugs.
-Chlorpromazine, mapazine.
-Antimetabolites and other drugs causing pancytopenia.
Bloodpicture: Neutropenia with toxic granules in neutrophils. Marrow shows decrease in granulocyte precursors with toxic granules in them.
Parathyroid hormone
Parathyroid hormone (PTH) is a polypeptide (84 amino acid residues) secreted by the chief cells of the parathyroid glands (four glands: two in each of the superior and inferior lobes of the thyroid; total weight 120 mg).
The main action of PTH is to increase serum calcium and decrease serum phosphate.
Its actions are mediated by the bones and kidneys -
In bone, PTH stimulates osteoclastic bone resorption and inhibits osteoblastic bone deposition. The net effect is the release of calcium from bone.
In the kidney, PTH has the following effects:
- Increases calcium reabsorption.
- Decreases phosphate reabsorption.
- Increases 1-hydroxylation of 25-hydroxyvitamin D (i.e. activates vitamin D).
PTH also increases gastrointestinal calcium absorption.
Roseola
- alias exanthem subitum; caused by Herpes virus type 6.
- children 6 months to 2 years old; spring and fall; incubation 10-15 days.
- sudden onset of a high fever with absence of physical findings; febrile convulsions are particularly common.
- fever falls by crisis on the 3rd or 4th day → 48 hours after temperature returns to normal macular or maculopapular rash starting on the trunk and spreading centrifugally.
Post viral (post hepatitic) cirrhosis (15-20%)
Cause:- Viral hepatitis (mostly HBV or HCV)
Acute hepatitis → chronic hepatitis → cirrhosis.
Pathology
Liver is shrunken. Fatty change is absent (except with HCV). Cirrhosis is mixed.
M/E :-
Hepatocytes-show degeneration, necrosis as other types of cirrhosis.
Fibrous septa -They are thick and immature (more cellular and vascular).
- Irregular margins (piece meal necrosis).
- Heavy lymphocytic infiltrate.
Prognosis:- - More rapid course than alcoholic cirrhosis.Hepatocellular carcinoma is more liable to occur
Glomerulonephritis
Characterized by inflammation of the glomerulus.
Clinical manifestations:
Nephrotic syndrome (nephrosis) → Most often caused by glomerulonephritis.
Laboratory findings:
(i) Proteinuria (albuminuria) and lipiduria—proteins and lipids are present in urine.
(ii) Hypoalbuminemia—decreased serum albumin due to albuminuria.
(iii) Hyperlipidemia—especially an increase in plasma levels of low-density lipoproteins and cholesterol.
Symptoms
severe edema, resulting from a decrease in colloid osmotic pressure due to a decrease in serum albumin.