NEET MDS Lessons
General Pathology
Hyperpituitarism
Causes
A. Pituitary; usually anterior lobe
1. Adenoma (the most common cause)
2. Hyperplasia
3. Carcinoma
B. Extra-pituitary causes
1. Hormone producing extra-pituitary tumors (ectopic hormone production)
2. Certain hypothalamic disorders
Pituitary adenomas are classified according to the hormone(s) produced by the neoplastic cells; these are detected by immunohistochemically-stained tissue sections. Pituitary adenomas can be functional (associated with hormone excess with their related clinical manifestations) or silent.
Pathogenesis
Guanine nucleotide-binding protein (G-protein) mutations are the best characterized molecular abnormalities. Such mutations eventuate in a persistent increase in intracellular cAMP, which is a potent mitogenic stimulus promoting cellular proliferation and hormone synthesis and secretion. In the setting of MEN-1 syndrome there are mutations in the MEN-1 (menin) gene.
Gross features
• Adenomas are usually soft & well-circumscribed
• Larger lesions extend superiorly through the sellar diaphragm compressing the optic chiasm and adjacent structures .
• Invasive adenomas refer to nonencapsulated tumors that infiltrate adjacent bone, dura, and even brain.
Microscopic features.
• Adenomas are composed of monomorphic, polygonal cells displayed in sheets, cords, or papillae. Their nuclei may be uniform or pleomorphic but the mitotic activity is scanty. The cytoplasm of the constituent cells may be acidophilic, basophilic, or chromophobic.
• The connective tissue is scanty that is why many lesions are soft & even gelatinous in consistency.
Prolactinomas are the most common type of hyperfunctioning pituitary adenoma.
Hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility.
Growth Hormone-Producing Adenomas (somatotroph cell adenomas) are the second most common type of functional pituitary adenoma. Because the clinical manifestations of excessive growth hormone may be subtle, the tumor may be quite large by the time they come to clinical attention. If such tumors occur before closure of epiphyses (prepubertal children), excessive levels of growth hormone result in gigantism. If elevated levels persist, or present after closure of the epiphyses, individuals develop acromegaly.
Corticotroph Cell Adenomas are mostly small (microadenomas) at the time of diagnosis. They may be clinically silent or cause hypercortisolism referred to as Cushing disease
Other Anterior Pituitary Neoplasms
• Gonadotroph adenomas (luteinizing hormone [LH]-producing and follicle-stimulating hormone [FSH]producing)
• Thyrotroph (thyroid-stimulating hormone [TSH]-producing) adenomas
• Nonfunctioning pituitary adenomas (hormone-negative (null cell) adenomas) Nonfunctioning adenomas constitute approximately 25% of all pituitary tumors; they typically present through their mass effects.
1. Pyogenic liver abscesses may be caused by E. coli, Klebsiella, Streptococcus, Staphylococcus, Bacteroides, Pseudomonas, and fungi.
Parasitic infections
1. Schistosomiasis is caused by different organisms in different parts of the world.
a. Clinical features include splenomegaly, portal hypertension, and ascites. Lesions are caused by the immune response to ova.
2. Amebiasis is caused by Entamoeba histolytica.
a. Clinical features include bloody diarrhea, pain, fever, jaundice, and hepatomegaly.
Drug-induced liver damage may be caused by agents that are direct hepatotoxins, such as carbon tetrachloride, acetaminophen, methotrexate, anabolic steroids, and oral contraceptive pills.
Haemolytic anaemia
Anemia due to increased red cell destruction (shortened life span)
Causes:
A. Corpuscular defects:
1.Membrane defects:
- Spherocytosis.
- Elliptocytosis.
2. Haemoglobinopathies:
- Sickle cell anaemia.
- Thalassaemia
- Hb-C, HBD, HbE.
3. Enzyme defects .deficiency of:
- GIucose -6 phosphate dehydrogenase (G6-PD)
- Pyruvate kinase
4. Paroxysmal nocturnal haemoglobinuria.
B. Extracorpusular mechanisms
1. Immune based:
- Autoimmune haemolytic anaemia.
- Haemolytic disease of new born.
- Incompatible transfusion.
- Drug induced haemolysis
2. Mechanical haemolytic anaemia.
3. Miscellaneous due to :
- Drugs and chemicals.
- Infections.
- Burns.
features of haemolytic anaemia
- Evidence of increased Hb breakdown:
-> Unconjugated hyperbilirubinaemia.
-> Decreased plasma haptoglobin.
-> Increased urobilinogen and stercobilinogen.
-> Haemoglobinaemia, haemoglobinuria and haemosiderinuria if Intravascular haemolysis occurs.
- Evidence or compensatory erythroid hyperplasia:
-> Reticulocytosis and nucleated RBC in peripheral smear.
-> Polychromasia and macrocytes
-> Marrow erythroid hyperplasia
-> Skull and other bone changes.
- Evidences of damage to RBC:
-> Spherocytes and increased osmotic fragility
-> Shortened life span.
-> Fragmented RBC.
-> Heinz bodies.
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
Metastatic Tumors
These are the most common malignant tumor of bone. Certain tumors exhibit a distinct skeletal prediliction. In adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney, and lung. In children, neuroblastoma, Wilms' tumor, osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma are the common sources of bony metastases. Most metastases involve the axial skeleton (vertebral column, pelvis, ribs, skull, sternum), proximal femur, and humerus. The radiologic appearance of metastases can be purely osteolytic, purely osteoblastic, or mixed osteolytic-osteoblastic (majority of cases). In lytic lesions (e.g., kidney& lung), the metastatic cells secrete substances such as prostaglandins, interleukins, etc. that stimulate osteoclastic bone resorption; the tumor cells themselves do not directly resorb bone. Similarly, metastases that elicit a blastic response (e.g., prostate adenocarcinoma) do so by stimulating osteoblastic bone formation.
Lupus erythematosus
- chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin and other systems.
- pathogenesis: light and other external agents plus deposition of DNA (planted antigen) and immune complexes in the basement membrane.
Histology:
- basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia) are vacuolated (liquefactive degeneration)
- thickening of lamina densa as a reaction to injury.
- immunofluorescent studies reveal a band of immunofluorescence (band test) in involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
- lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.
Peutz-Jeghers syndrome
1. Lesions appear as small, melanotic, and freckle-like. They can be found on the skin, oral mucosa, lips, feet, and hands.
2. May also present with intestinal polyps, which may develop into a gastrointestinal carcinoma.
3. Genetic transmission: autosomal dominant.