TEST

• There are Two morphologic types with prognostic significance:

  Chronic persistent hepatitis and asymptomatic carrier.
• •Chronic Persistent Hepatitis:


  •Mild form characterized by lymphocytic infiltration in portal tracts.

  •About half of HBV-infected individuals exhibit this type, not progressing to severe disease.

  •Others with little portal change are termed "normal" or "asymptomatic" HBV carriers.

  •They show minimal or sporadic increases in serum aminotransferase
• •Asymptomatic Carrier:


  •Represents the most inactive extreme of persistent viral hepatitis spectrum.

  •Characterized by intact limiting plate.

  •Liver cell necrosis and lobular inflammation are minimal; Kupffer cells appear normal.

  •Scattered cells display a large granular eosinophilic cytoplasm containing an abundant of HBsAg (Ground glass" hepatocytes )

  •No "ground glass" hepatocytes in chronic hepatitis C.

  -Instead, fatty change/steatosis of liver cells is a constant finding
• •Chronic Active Hepatitis: definition and early stage


  a Necrotizing inflammatory disease potentially progressing to cirrhosis.

  Early: in the course of the disease: Chronic inflammation and focal necrosis are distributed irregularly among lobules without being  predominantly centrilobular as in acute viral hepatitis
• chronic active nephritis - later stage 


  •Portal tracts are densely infiltrated by lymphocytes, macrophages, and occasional plasma cells.

  •Inflammatory cells penetrate the limiting plate, surrounding individual hepatocytes and groups at portal tract borders.

  •The resulting Irregular appearance of periportal zone ("moth-eaten") is termed piecemeal necrosis, Considered a hallmark of progressive disease.

  •The Expanded portal tracts exhibit mild to severe bile duct proliferation, likely a nonspecific response to lobular changes.
• .•Its common to see Intralobular Changes: Similar to acute hepatitis, including single cell necrosis, acidophilic bodies, ballooned hepatocytes, and central phlebitis.
• •End-stage Cirrhosis: is characterised by Dense collagenous septa which destroy lobular architecture, dividing the liver into hepatocellular nodules, termed cirrhosis
• •Confluent Hepatic Necrosis:


  in the form of Bridging necrosis in chronic active hepatitis indicates rapid progression to cirrhosis.

  •Strands of connective tissue extend from portal tracts into lobules, giving a stellate appearance

  •Threads of connective tissue envelop single hepatocytes and groups, particularly near portal tracts.

  •In patients with chronic active hepatitis B "Ground glass" cells are scarce in areas of necrosis and inflammation, presumably destroyed by immune response.
• 4 mechanisms involved in the production of hepatic cirrhosis:


  1.Hepatocellular necrosis

  2.Replacement fibrosis and inflammation

  3.Vascular derangement

  4.Hyperplasia of surviving liver tissue – liver cells, forming irregular nodules and respectively, ductules epithelium – hyperplasia of bile ducts
• Cirrhosis gross examination


  •on gross examination the liver is shrunken, firm, with rough surface due to the nodules formation

  •Micronodular Type:

  •Small nodules (<3 mm) separated by thin fibrous septa.

  •Historically termed Laennec's or nutritional cirrhosis.

  •Macronodular Type:

  •Nodules of varying size, some several cm in diameter.

  •Broad bands or areas of depressed scarring.

  •Previously labelled post-necrotic or posthepatitic cirrhosis.

  •Mixed (Micro-Macronodular) Cirrhosis.
• •Hepatocellular carcinoma - clinically, risk factors


  is the most common primary malignant tumor of the liver

  •Clinically: there is an Increase in liver volume, hepatic pain, ascites, portal vein thrombosis, hepatic vein occlusion, esophageal varicose veins etc.

  •Risk factors for the development of hepatocarcinoma include hepatitis B or C infection, alcoholic cirrhosis, other cirrhosis types, hemochromatosis, α1-antitrypsin deficiency, exposure to aflatoxins, and polyvinyl chloride.
• •hepatocellular carcinoma Macroscopically:


  •Usually appears as a single, voluminous nodular mass, soft, yellowish-haemorrhagic, often with a greenish tint due to bile impregnation.

  •Less commonly presents as multifocal tumor or diffuse infiltrative cancer, sometimes affecting the entire liver, especially in cirrhotic cases.
• hepatocellular carcinoma microscopically


  •Typically trabecular (sinusoidal) carcinoma with thick trabeculae of hepatocytes separated by sinusoids.

  •Acinar or pseudoglandular subtype features hepatocytes arranged in glandular structures.

  •Acidophilic hyaline inclusions similar to Mallory bodies and bile may be present in hepatocyte cytoplasm.

  •Mixed pattern with trabecular and acinar areas is common.

  •Scirrhogenous carcinomas have a rich connective stroma.

  •Poorly differentiated carcinomas have cells with marked nuclear pleomorphism, sometimes with anaplastic giant cells.
• hepatocellular carcinoma - diagnostic markers 


  •No specific IHC markers.

  •Useful markers to establish a diagnosis include α-fetoprotein (AFP), α1-antitrypsin (α1-AT), carcinoembryonic antigen polyclonal (CEAp), Hepatocyte paraffin-1 (Hep Par-1), and glypican-3 (Gly-3) in difficult cases.
• Hepatocellular carcinoma:

  •Has a High tendency to invade vessels, often extending into portal vein or hepatic veins, and sometimes reaching the inferior vena cava and right atrium.

  •Tumor often reaches appreciable sizes before metastasizing.

  •Intrahepatic metastases are characteristic, while extrahepatic ones mainly affect periportal lymph nodes and lungs.
• •Nephrotic syndrome is characterised by:


  •Heavy proteinuria, defined as the excretion of more than 3.5 g of protein per 24 hours.

  Results in hypoproteinaemia, hypoalbuminemia, and peripheral edema.

  Together these 3 clinical findings comprise the classic nephrotic syndrome•

  Often accompanied by a 4th symptom: hyperlipidaemia.

  •Majority of cases arise from glomerular diseases categorized as noninflammatory glomerulopathies.

  •"Pure" nephrotic syndrome lacks features of the nephritic syndrome.
• •Nephritic syndrome is characterised by:


  •Haematuria, either microscopic or visible grossly.

  •Variable degrees of proteinuria (under 3.5 g/day).

  •Oliguria and decreased glomerular filtration rate, leading to elevated levels of blood urea nitrogen and serum creatinine.

  •Salt and water retention commonly causing hypertension and edema

  .•The nephritic syndrome is Typically associated with inflammatory glomerular disease, specifically glomerulonephritis.
• •Chronic pyelonephritis 


  is a chronic tubulointerstitial disorder characterized by gross, irregular, and often asymmetric scarring, along with deformation of the calyces and the overlying parenchyma.

  •It frequently progresses to end-stage kidney, marked by kidney shrinkage and fibrosis, resulting in insufficient renal function.

  •Approximately 15% of patients requiring renal dialysis or transplantation have chronic pyelonephritis.
• •Chronic pyelonephritis is categorized into cases with and without obstruction.

  •In mechanical Obstructive cases they exhibit dilation of all calyces and the renal pelvis, with uniformly thinned parenchyma, termed hydronephrosis, due to a combination of obstruction and infection.

  •Cases without obstruction, largely associated with vesicoureteral reflux (reflux nephropathy), calyces from the kidney poles are expanded, and associated with discrete to coarse scars that  cause renal surface indentation.
• •Chronic pyelonephritis - Microscopic changes


  primarily affect tubules and interstitium.

  •Tubules exhibit atrophy, hypertrophy, or dilatation in certain areas.

  •Dilated tubules may contain hyaline casts resembling colloid-containing thyroid follicles, termed "thyroidisation".

  •Chronic interstitial inflammation and fibrosis vary in severity.

  •Glomeruli may be unaffected, may show periglomerular fibrosis, or be sclerotic.

  •Arcuate and interlobular vessels reveal obliterative endarteritis in scarred areas, with hyaline arteriolosclerosis observed throughout the kidney in cases of hypertension.
• Testicular tumors: Seminoma 


  -is a common germinal tumor

  •It has a Homogeneous, gray-white, lobulated cut surface, often replacing the entire testis in over half of cases.

  •Typically does not penetrate the tunica albuginea.

  •Microscopically, features sheets of uniform "seminoma cells" arranged into poorly demarcated lobules by delicate fibrous tissue septa containing lymphocyte infiltration

  •"Seminoma cells" are large, round-to-oval with distinct cell membrane, clear or watery-appearing cytoplasm, and large, central hyperchromatic nucleus.

  •Mitoses are infrequent.
• •Male Teratomas:


  - it’s a common germinal tumor

  •Grossly are large, ranging from 5 to 10 cm in diameter, with heterogeneous appearance of solid areas interspersed with cysts.
• •Histologically, three variants are recognized based on cellular differentiation: -explain 1 


  1.Mature teratomas: Composed of differentiated cells or organoid structures such as neural tissue, muscle bundles, cartilage islands, squamous epithelium clusters, structures resembling thyroid gland, bronchial or bronchiolar epithelium, and bits of intestinal wall, within a fibrous or myxoid stroma.
• •Histologically, three variants are recognized based on cellular differentiation: explain 2 and 3

  2.Immature teratomas: Intermediate stage between mature teratoma and embryonal carcinoma, formed by elements of all three germ cell layers, incompletely differentiated and lacking organoid arrangement.

  3.Teratomas with malignant transformation.
• •Nodular Prostatic Hyperplasia (Benign Enlargement):


  •It’s a Common disorder in men over age 50, characterized by the formation of  large nodules in periurethral region with partial or complete obstruction of urinary flow.

  •Hyperplasia involves both glandular tissue and fibromuscular stroma.

  •Nodules appear exclusively in the middle and lateral lobes of the periurethral zone, weighing about 100 g, varying in colour and consistency.
• nodular prostatic hyperplasia

  •Glandular proliferation nodules have yellow-pink, soft, sponge-like tissue exuding milky white prostatic fluid; fibromuscular nodules are pale Gray, tough, and lack fluid exudation.
• nodular prostatic hyperplasia - microscopically 


  •nodularity is caused by glandular proliferation (adenoma) and or glandular dilation or by  fibro-muscular proliferation of the stroma(fibroma, leiomyoma) or more frequently  hyperplasia of all three tissues (fibroleiomyoadenoma).

  •Epithelial proliferation predominates, forming aggregations of small to large cystically dilated glands lined by two cellular layers: inner columnar and outer flattened epithelium, with intact basement membrane; characteristically has papillary buds and infoldings.
• •Hyperplasia (Benign Enlargement): Complications: 


  •Compression of urethra leading to difficulty in urination, chronic retention of urine, and attacks of acute retention, often exacerbated by urinary infection causing edema and congestion of prostatic urethra.

  •Cystitis and pyelonephritis.

  •Secondary changes in bladder: hypertrophy, trabeculation, diverticulum formation, and stones.

  •Hydronephrosis.
• •Endometritis in the Uterine Body:


  •The inflammation of the endometrium is a Histologic diagnosis based on abnormal inflammatory cell infiltrate in the endometrium, its distinguished from normal presence of polymorphonuclear leukocytes during menstruation and mild lymphocytic presence.
• Acute endometritis is associated with parturition and septic abortion, infection at the time of parturition is commonly associated with with retention of products of conception

  •In the case of abortion, another factor is the introduction of infection by criminal interference

  •Mixed bacterial flora including pyococci, coliform organisms, and proteus are present

  •Acute inflammatory changes include vascular hyperaemia, massive polymorph infiltration, and edema; curettage is often diagnostic and curative as it removes the necrotic tissue that has served as the nidus of ongoing infection
• endometritis complications:


  
  

  1. Puerperal sepsis.
  2. Myometritis.
  3. Parametritis with iliac venous thrombosis.
  4. Salpingitis leading to tubal blockage and infertility.
  5. Peritonitis via fallopian tube, though rare due to antibiotic era.
• •Chronic Endometritis:


  •Is Associated with intrauterine device use, pelvic inflammatory disease, and retained products of conception after an abortion or delivery.

  •Histopathological diagnosis is based on presence of plasma cells in endometrium; generally the condition is self-limited.
• •Tuberculous Endometritis:


  •When Bacillary infestation spreads from fallopian tubes or bloodstream in generalised miliary

  •Tubercles shed monthly if menstruation continues; may cease with caseation in some cases.
• •Endometriosis is:


  •The Presence of benign endometrial glands and stroma outside the uterus.

  •Most common sites: ovaries, uterine ligaments, pouch of Douglas, pelvic peritoneum.

  •Can also involve cervix, vagina, perineum, bladder, umbilicus, pelvic lymph nodes, and rarely distant areas like lungs, pleura, small bowel, kidneys, and bones.
• •Pathogenesis of endometriosis:


  •Theories include menstrual implantation – foci of menstrual endometrium regurgitate through the fallopian tubes and implant on the various pelvic organs,

  intraoperative implantation – following hysterectomy and episiotomy, lymphatic and hematogenous dissemination.
• •Appearance and Diagnosis of endometriosis:


  •Endometriosis in ovaries and peritoneal surface appears as red or bluish nodules, 1 to 5 mm in size.

  •Since the ectopic endometrial glands often participate in the menstrual cycle, Repeated bleeding leads to deposition of hemosiderin, causing gross brown discoloration.

  •Microscopically the diagnosis is based on presence of ectopic endometrial glands and stroma; sometimes healed foci may consist of fibrous tissue and hemosiderin-laden macrophages.
• Endometrial Hyperplasia is a precancerous condition where there is an irregular thickening of the lining of the uterus, they are classified into 3 types: simple, complex and atypical
• •Simple Hyperplasia (Cystic or Mild):


  
  

  • a proliferative lesion that shows Minimal glandular complexity and crowding, but no cytologic atypia.
  • Some Glands may be straight, small tubular structures lined by a tall, basophilic, one cell layer thick. Others are cystically dilated with subsequent epithelial atrophy.
  • The Abundant endometrial stroma is composed of spindle cells with scant cytoplasm.
  • Interstitial edema and haemorrhages present.
  • 1% of cases progress to adenocarcinoma.
• •Complex Hyperplasia: 


  
  

  • previously called moderate hyperplasia:
  • Exhibits Severe glandular complexity and crowding, but no cytologic atypia.
  • Increased number and varying size of glands, with scanty stroma.
  • 3% of cases progress to adenocarcinoma.
• •Atypical Hyperplasia 


  – previously called Severe hyperplasia:

  • Displays cytologic atypia and marked glandular crowding.
  • Irregular glands, papillary intraluminal projections, undergo "budding" with finger-like outpouchings.
  • Epithelial lining exhibits stratification, scalloping, tufting; cells are enlarged, hyperchromatic, with increased nuclear-cytoplasmic ratio.
  • 33% of cases progress to adenocarcinoma.