Gupta - Pathology Flashcards

Question

What is this? Describe 3 types.

Answer 1

- **Esophageal diverticulum**: outpouching of mucosa through muscular layer of the esophagus - Can be asymptomatic or cause dysphagia and regurgitation - Dx by _barium swallow_; sx repair rarely required - Several types, each of different origin: 1. _Zenker (pharyngeal)_: posterior outpouchings of mucosa/submucosa through cricopharyngeal muscle; lack of coordination b/t pharyngeal propulsion and cricopharyngeal relaxation 2. _Midesophageal (traction)_: traction from mediastinal inflam lesions or motility disorders 3. _Epiphrenic_: just above diaphragm and usually accompanies motility disorder (achalasia, diffuse esophageal spasm)

Answer 2

- **Thyroglossal duct cyst**: thyroid anlage begins in _foramen cecum_ at base of tongue, and descends to midline location in anterior neck in devo - Remnants can persist, and are lined by stratified squamous epi when located near base of tongue, or pseudostratified columnar epi in lower locations -\> variable histo appearance makes _anatomic location_ important for diagnosis - CT wall of cyst may harbor lymphoid aggregates or remnants of recognizable thyroid tissue -\> tx is EXCISION

Answer 3

- **Viral esophagitis** - GROSS: postmortem specimen with multiple, overlapping _herpetic ulcers_ in the distal esophagus - TOP RIGHT: multinucleate squamous cells containing _herpesvirus_ nuclear inclusions - BOTTOM RIGHT: _CMV_-infected endothelial cells with nuclear and cytoplasmic inclusions -\> can be a real problem in people with UC and Crohn's

Answer 4

- **Condyloma acuminatum**: can be precursor lesions to pure squamous cell carcinoma of the anal canal (freq associated w/_HPV infection_) - DIVISIONS (1/3rds): 1. Upper zone: columnar rectal epi 2. Middle: transitional epithelium 3. Lower: stratified squamous epi -\> below dentate/pectinate line (palpable on exam) - NOTE: carcinomas of anal canal may have typical glandular or squamous patterns of differentiation 1. Tend to be squamous below dentate line, but more mucosal, and adeno above (only 5%)

Answer 5

- **Diaphragmatic hernia**: incomplete formation of the diaphragm allows abdominal viscera to herniate into the thoracic cavity - When severe, space-filling effect of the displaced viscera _can cause pulmonary hypoplasia_ that is incompatible with life - Liver in thoracic cavity in image on the front of card, and bowel in left side of the thoracic cavity in the attached imaging

Answer 6

- **Branchial (cervical lymphoepithelial) cyst**: vast majority thought to arise from remnants of _2nd branchial arch_ -\> young adults (20-40-y/o) - _Upper, lateral_ aspect of the neck along the sternocleidomastoid (SCM) muscle - MICRO: fibrous walls, usually lined by stratified squamous or pseudostratified columnar epithelium 1. Cyst wall typically contains lymphoid tissue with prominent _germinal centers_

Answer 7

- **Esophageal graft-vs-host disease** - HISTO features similar to those in skin, and include: 1. Basal epithelial cell apoptosis, 2. Mucosal atrophy, and 3. Submucosal fibrosis without significant acute inflam infiltrates (ex: in skin biopsy, can have just 1-2 lymphos and some _dyskeratotic cells_) - Going to see these effects in squamous mucosa b/c turning over rapidly -\> GI tract a key region

Answer 8

- **Hairy leukoplakia**: hyperkeratosis + acanthosis (diffuse epidermal hyperplasia) - “Balloon” (glycogenated) cells in the upper spinous layer - Elongation of the epidermis

Answer 9

- **Upper 1/3rd of esophagus** -\> inlet patch: generally asymptomatic, but gastric mucosal acid can cause dyphagia, esophagitis, Barrett's, or adenocarcinoma (rarely) 1. Can also mimic invasive cancer b/c may be present in any layer of the wall - _Gastric heterotopia_ (small patches of ectopic gastric mucosa in small bowel, colon) may present w/occult blood loss b/c peptic ulceration of adjacent mucosa - NOTE: ectopic pancreatic tissue less common, but can be found in esophagus or stomach

Answer 10

- Note that the SCC in the last set of images is invasive - _Molecular_: p16 -\> p53 -\> Cyclin D

Answer 11

- **Sialolith** (stone) -\> can cause **chronic sialadenitis** if recurrent or persistent ductal obstruction - Episodic pain and swelling, usually at mealtime - Submandibular involvement may include persistent enlargement - _Tx_: sialolith removal, if appropriate 1. Sx removal of the gland may be indicated for chronic sialadenitis

Answer 12

- **Squamous cell carcinoma**: most common anorectal malignancy -\> _HPV-16_ 1. Atypical cells infiltrating into the mucosa - NOTE: adenocarcinoma only 5% of anorectal malignancies, and associated with _HPV-18_

Answer 13

- **Cholesteatoma**: assoc w/chronic otitis media - _Non-neoplastic_, cystic lesions 1-4 cm in diameter, lined by _keratinizing stratified squamous epithelium_ or metaplastic mucus-secreting epithelium, and filled with amorphous debris - Can erode locally and cause destruction in middle and internal ear - Like an epidermal inclusion cyst in the ear

Answer 14

- **Boerhaave syndrome**: less common, but more serious than Mallory-Weiss tears; characterized by transmural _tearing and rupture_ of distal esophagus - Catastrophic event produces _severe mediastinitis_ and generally requires SX INTERVENTION - B/c pts can present w/severe chest pain, tachypnea, and shock, initial differential diagnosis can include myocardial infarction - Contrast extravasation from distal esophagus in the image on front of the card

Answer 15

- **Hairy leukoplakia**: not uncommonly the first sign of systemic disease (as oral lesions often are) - Distinctive oral lesion on _lateral border of tongue_ - Associated with immunocompromised patients - Caused by _EBV_ - Unlike thrush (candida), it _can't be scraped off_

Answer 16

- Acute appendicitis with *Enterobius vermicularis* (pinworm) - NOTE: kids, in general, have more germinal centers and lymphos in their GI tract

Answer 17

- Age 50-60 - _Mucous cells_ - Neutro and lympho inflammation - Similar symptoms to chronic gastritis - Risk factor: H pylori - Occasional association w/gastric adenocarcinoma

Answer 18

- **Muscle hypertrophy**, so outlet obstruction from the stomach -\> can go in and correct this surgically - 3-5x more comm in males; 1 in 300-900 live births - Generally presents b/t _3rd and 6th wks of life_ as new-onset regurgitation, _projectile, non-bilious vomiting_ after feeding, freq demands for re-feeding - Physical exam reveals firm, ovoid, 1-2cm _abdominal mass_

Answer 19

- _Clinical manifestations_: abdominal pain, distention, vomiting, and constipation - HERNIAS: most frequent cause worldwide - INTUSSUSCEPTION: most comm cause in _kids \<2_; infant cries from abdominal pain, then is fine, then relapses (can also have bloody stool and sausage feeling on palpation in PE) - VOLVULUS: intestine doesn’t adhere to abdominal wall correctly, and can get twisted around itself (more common in _children_) - ADHESIONS: post-surgery

Answer 20

- **Carcinoid tumor**: most common tumor of appendix - _Nested, bland cells_ with salt and pepper chromatin, like all NE tumors - Usually incidental, and almost always BENIGN - GROSS: frequently forms _solid, bulbous swelling at distal tip_ of the appendix (see attached) 1. Golden, yellow appearance - Although intramural and transmural extension may be evident, _nodal metastases are very infrequent_, and distant spread is exceptionally rare

Answer 21

- **Dentigerous cyst**: originates around crown of an unerupted tooth - RADIOGRAPH: _unilocular lesions_ (1 chamber) most often assoc w/impacted 3rd molar (wisdom) teeth - HISTO: lined by thin layer of stratified squamous epithelium w/dense chronic inflam cell infiltrate - TX: complete removal of the lesion is curative - Association with _ameloblastoma_ -\> locally invasive tumors in mandible, radiolucent “soap bubble”

Answer 22

- **Pleomorphic adenoma**: middle-age F w/painless, slow-growing, movable, non-tender, firm mass - Typically round, well-circumscribed, and may have a rubbery texture - Benign mixture of ductal (epi) and myoepithelial cells -\> both _epi AND mesenchymal_ differentiation - NOTE: carcinomas can arise in these -\> sudden rapid growth (aka, carcinoma ex pleomorphic adenoma)

Answer 23

- **Pleomorphic adenoma**: benign mixture of ductal (epi) and myoepi cells -\> both _epi and mesenchymal_ differentiation - Epithelial elements dispersed throughout matrix, and varying degrees of _myxoid, hyaline, chondroid_ (cartilaginous), and even osseous tissue - Epithelial component + background mucin-like supporting material common - May advance to carcinoma, in some cases

Answer 24

- Pleomorphic adenoma (50%): mixed tumor - Mucoepidermoid carcinoma (15%) - Warthin tumor (5-10%)

Answer 25

- **Acute appendicitis**: appendix is a normal true diverticulum of cecum prone to acute/chronic inflam - Initiated by progressive _INC in intraluminal pressure_ that compromise venous outflow 1. 50-80% of cases associated with overt luminal obstruction, usually by a FECALITH: small stone-like mass of stool - DX: requires _neutro infiltration of muscularis propria_ (inflam throughout the wall) 1. Mucosa shows ulceration and undermining by an extensive neutrophilic exudate here - PRESENTATION: epigastric pain that slowly moves to right lower quadrant

Answer 26

- **Fungal esophagitis**: almost always Candida - Parakeratosis of the esophagus - Acute inflammation: may be less in young, or immunosuppressed people - Pseudohyphae diving down in the attached image

Answer 27

- **Mucinous neoplasm** in the appendix - Typically display a circumferential growth pattern in appendiceal mucosa w/variable papillary architecture - Glands much more elongated, and more cytoplasm: spitting out mucin - This example is probably benign

Answer 28

- **Meckel diverticulum** (ileum): failed involution of the vitelline duct (involves all 3 layers) - _Law of 2's_: 2% of the population 1. Within 2 feet (60 cm) of the ileocecal valve 2. About 2 inches (5 cm) long 3. Twice as common in _males_ 4. Most often symptomatic by _age 2_ (only about 4% are ever symptomatic) - _Can have ectopic tissue_ in these, which can make them symptomatic

Answer 29

- **Warthin tumor**: middle-age M smokers; painless - Benign, but can be bilateral; almost exclusively in the parotids - _Epithelial + lymphoid_ elements -\> follicular germinal center beneath the epithelium - Cystic spaces separate lobules of neoplastic epi consisting of _double layer of eosinophilic epithelial cells_ based in a reactive lymphoid stroma - Often do _FNA_ and describe what they pull out as “_motor oil_” -\> dark, thick fluid (cystic)

Answer 30

- Nodular hyperplasia(s) - Benign neoplasms 1. Hepatocellular adenomas 2. Hemangiomas - Malignant Tumors: 1. Hepatoblastoma 2. Hepatocellular Carcinoma (HCC) 3. Cholangiocarcinoma (CCA) 4. Other Primary Hepatic Malignant Tumors 5. Metastasis: colon, lung, and breast

Answer 31

- **Focal nodular hyperplasia**: well-demarcated, but poorly encapsulated nodule, up to many cm in diameter -\> "central scar" is the buzz word - _Spontaneous_ mass lesion in an otherwise normal liver, most often in YOUNG to middle-aged adults - Central gray-white, depressed _stellate scar_ from which fibrous septa radiate to the periphery - Not much clinical significance

Answer 32

- TYPES: 1) focal nodular hyperplasia and 2) nodular regenerative hyperplasia - COMMON FACTOR: focal or diffuse alterations in hepatic blood supply, arising from: 1. Obliteration of portal vein radicles, and 2. Compensatory augmentation of arterial blood supply - NOTE: FNH doesn't have much clinical significance vs. NRH, which can cause portal HTN

Answer 33

- **Focal nodular hyperplasia**: broad _fibrous scar_ with hepatic arterial and bile duct elements - _Chronic inflammation_ in parenchyma lacking normal architecture due to hepatocyte regeneration - A little bit of duct hyperplasia: reactive process

Answer 34

Focal nodular hyperplasia: all bile ducts in the fibrous area with inflammation

Answer 35

- **Nodular regenerative hyperplasia**: trichrome highlights compressed central veins - Denotes liver entirely transformed into nodules: grossly similar to micronodular cirrhosis, but _w/o fibrosis_ - Can lead to devo of portal HTN - Association with _conditions affecting intrahepatic blood flow_, incl. solid-organ (esp. renal) transplant, hematopoetic stem cell transplant, and vasculitis - Usually incidental finding

Answer 36

- **Nodular regenerative hyperplasia**: gross (left) and cut (right) appearance - May resemble cirrhosis grossly - Nodules less well-defined in the cut appearance; parenchyma softer than in cirrhosis, and fibrous septa lacking

Answer 37

- **Nodular regenerative hyperplasia**: nodule in the center of the field in which _plates in center of the field are wide_, and plates at the edge are narrowed 1. This change, in the absence of significant fibrosis, is indicative of nodular regenerative hyperplasia 2. Silver stain highlights _reticulin framework_ of liver: can be difficult to see this w/o this stain - Normally liver cell plates (lined by dark-staining reticulin fibers) should be of equal width -\> 1 hepatocyte wide - Sinusoids full of proteinaceous material - NO inflammation, unlike FNH

Answer 38

- **Nodular regenerative hyperplasia**: micro plump hepatocytes surrounded by rims of atrophic hepatocytes - Sinusoidal dilation present (arrows); filled with proteinaceous material - No inflammatory infiltrate or areas of necrosis

Answer 39

- **Nodular regenerative hyperplasia**: reticulin staining highlights characteristic pattern of atrophic hepatic cords (left) and plump, thickened cords (right)

Answer 40

- **Cavernous hemangioma**: BENIGN blood vessel tumors identical to those occurring elsewhere - MOST COMMON benign liver tumors - HISTO: blood-filled _vascular_ channels (dilated vessels) separated by a dense, fibrous stroma - GROSS: discrete, red-blue, soft nodules, usually _\<2cm_ in diameter, and generally located _directly beneath the capsule_, so **prone to rupture**, making them clinically significant 1. NUTMEG color: alternating light and dark colors -\> means there is congestion

Answer 41

- **Hepatocellular adenoma**: benign, and devo from hepatocytes -\> both oral contraceptives (OC's) and anabolic steroids are assoc w/devo of these - Incidental, or can cause pain w/rapid growth; rather well-circumscribed - Rupture is a surgical emergency - HISTO: cords of hepatocytes with an arterial vascular supply (arrow), and NO PORTAL TRACTS

Answer 42

- _Hepatocellular adenoma_: cords of hepatocytes, with an arterial vascular supply (arrow) and no portal tracts

Answer 43

- Based on MOLECULAR CHANGES - **HNF1-alpha inactivated**: virtually no risk of malignant transformation, often associated w/oral contraceptive use or in ppl w/_MODY-3_ - **β-Catenin activated**: muts in β-catenin gene, leading to marked atypia, and assoc with a very _high risk for malignant transformation_ - **Inflammatory**: hallmark is up-regulation of _CRP_ (C-reactive protein) and serum amyloid A (_SAA_; often derived from gp130 mutations) 1. 10% have concomitant β-catenin activating mutations; intermediate risk for malignant transformation

Answer 44

- **Hepatoblastoma**: most common liver tumor of early childhood (\<3-y/o), and resemble fetal liver - Can be epithelial or mixed with mesenchymal elements (osteoid (favorable), cartilage) - Frequent activation of **WNT** pathway: association with APC/Familial adenomatous polyposis (FAP) 1. Also associated with Beckwith-Wiedemann (overgrowth disorder) and hemi-hypertrophy - Fatal if untreated; sx + chemo = 80% 5-yr survival - Variable clinical presentation

Answer 45

- **Hepatoblastoma**: normal liver on the left, and abnormal on right with a pseudopapillary look - See attached gross appearance

Answer 46

- **Hepatocellular carcinoma** (HCC): high assoc with Hep B and Hep C, chronic liver disease - _Cirrhosis NOT mandatory_ for hepatocarcinognesis - Also seen with aflatoxin (Aspergillus) and alcohol 1. Synergistic effect - Activation of **β-catenin** and inactivation of **p53** are the two most common early mutational events - More common in MALES (5th most deadly cancer) - INC _alpha fetal protein_ (50%) b/c liver can make this - GROSS: yellow-tan, kind of nodular appearance; even outside liver appears a little abnormal and nodular here - MICRO: if well-differentiated, can look almost exactly like normal liver 1. _Degenerating hepatocyte_ in bottom image

Answer 47

- Small cell vs. large cell and low-grade vs. high-grade really not that important for us to know - Wouldn't spend too much time on this chart...

Answer 48

- **Fibrolamellar variant** of HCC: - 85% occur under age 35-y/o, and w/o gender predilection or identifiable pre-disposing conditions 1. Kids, but older than hepatoblastoma - Malignant hepatocytes in dense, fibrous stroma 1. Can see some cholestasis here too 2. Scarring, fibrotic gross/micro appearance

Answer 49

- Gross appearance of fibrolamellar variant of HCC - Scarring, fibrotic gross and micro appearance

Answer 50

- **Nodule-in-nodule** growth in distinctively large nodule of Hep-C-related cirrhosis 1. Suggests an EVOLVING CANCER - HISTO: top half moderately differentiated HCC, and bottom half well-differentiated HCC 1. Moderately differentiated: bigger nuclei, a little more pleomorphic, look for mitotic figures 2. Well-differentiated can be difficult to distinguish from "normal" liver tissue

Answer 51

- **Cholangiocarcinoma** (CCA): 2nd most common 1^o malignant liver tumor after HCC -\> malignancy of biliary tree, arising from bile ducts w/in and outside the liver - Perineural invasion in image on the right, and _desmoplasia_ in the left image - All risk factors for CCA cause chronic inflam and cholestasis - Perihilar tumors = _Klatskin tumors_ (50%) - _Premalignant lesions_ for CCA are also known, the most important of which are biliary intraepithelial neoplasias (low to high grade, BilIN-1, -2, or -3). - Associated with liver flukes (infection) such as *Opisthorchis* and *Clonorchi* (uncommon in the US)

Answer 52

- **Cholangiocarcinoma** (CCA): often make MUCIN - Most well- to moderately-differentiated w/clearly defined _glandular/tubular structures_ lined by malignant epithelial cells 1. _Prominent nucleoli_: can be a giveaway that this is malignant 2. Not all sitting on BM: moving toward luminal space - Typically incite marked _desmoplasia_ - Lymphovascular invasion and perineural invasion are both common

Answer 53

- ANGIOSARCOMA: resembles those occurring elsewhere, and has historical associations with vinyl chloride, arsenic, or Thorotrast 1. These are mostly mets to the liver now - EPITHELIOID HEMANGIOENDOTHELIOMA: another form of endothelial malignancy; has a much more variable prognosis than the almost uniformly fatal angiosarcoma - HEPATIC LYMPHOMAS: primarily diseases of middle-aged men, and seen, albeit rarely, in assoc w/Hep B and C, HIV, and PBC 1. Most are diffuse large B-cell lymphomas, followed by MALT lymphomas. - HEPATOSPLENIC DELTA-GAMMA T-CELL LYMPHOMA: most common in young adult males, and has a predilection for hepatic and splenic sinusoids as well as the marrow 1. Think of this when you sinusoids packed full of lymphos

Answer 54

- **Metastases to the liver**: involvement of the liver by metastatic malignancy is far more common than primary hepatic neoplasia - Most common primary sources are the colon, breast, lung, and pancreas

Answer 55

- **Cholestasis**: systemic retention of bilirubin and other solutes eliminated in the bile - Caused by impaired bile formation and bile flow that gives rise to accumulation of bile pigment in the hepatic parenchyma - Can be caused by extrahepatic or intrahepatic obstruction of bile channels, or by defects in hepatocyte bile secretion

Answer 56

- Emulsification of dietary fat in the lumen of the gut through the detergent action of bile salts, and - The elimination of bilirubin and other waste products - RBC’s alive about 120d, then digested by macros, and unconjugated bilirubin complexed to albumin (b/c not water-soluble), sent to liver and conjugated

Answer 57

- See attached image for steps 1-3 - Step 4: _glucuronidation_ generates bilirubin monoglucuronides and diglucuronides, which are water soluble and readily excreted into bile 1. Big deal is whether conjugated or not: this distinction will help you discriminate b/t different diseases - Step 5: gut bacteria deconjugate bilirubin and degrade it to colorless urobilinogens - Step 6: urobilinogens and residue of intact pigments are excreted in the feces, with some reabsorption and excretion into urine

Answer 58

- When there is bilirubin overproduction, hepatitis, or obstruction of the flow of bile = disruption of the equilibrium between bilirubin production and clearance

Answer 59

- CONJUGATED: not quite as big a deal, and not as bad for tissue b/c excreted in urine/feces 1. Choledocholithiasis: impaired bile duct flow/obstruction 2. Deficiency of canalicular membrane transporters (Dubin-Johnson syndrome, Rotor syndrome) 1. Impaired bile flow from duct obstruction or autoimmune cholangiopathies - UNCONJUGATED: bigger deal, and can accumulate in tissues -\> liver can't keep up 1. Typically bound to albumin, but small fraction of unbound is the problem 2. Can go into brain, and cause _kernicterus_, creating yellow color (esp. in kids): physiologic jaundice of newborn -\> can’t get rid of heme breakdown products/bilirubin fast enough 3. _Excess production of bilirubin_: hemolytic anemias, resorption of blood from internal hemorrhage (e.g., alimentary tract bleeding, hematomas), ineffective erythropoiesis (e.g., pernicious anemia, thalassemia) 4. _Reduced hepatic uptake_: drug interference with membrane carrier systems, some cases of Gilbert syndrome 5. _Impaired bilirubin conjugation_: physiologic jaundice of the newborn (decreased UGT1A1 activity, decreased excretion), breast milk jaundice (β-glucuronidases in milk), genetic deficiency of UGT1A1 activity (Crigler-Najjar syndrome types I and II), Gilbert syndrome (need add'l insult to know they have it), diffuse hepatocellular disease

Answer 60

- _Gilbert_: most pts don’t ever know they have this until they have an additional insult - _Dubin-Johnson_: black liver -\> pigmented, cytoplasmic globules (conjugated bilirubin) - _Rotor_: not much clinical significance (babies)

Answer 61

- **Dubin-Johnson Syndrome**: impaired excretion of bilirubin glucuronides b/c canalicular membrane-carrier defect (**MRP2**: multidrug resistance protein 2 mutation) - Darkly pigmented cytoplasmic globules in liver: ton of bile within the hepatocytes - Innocuous clinical course

Answer 62

- Bile plug due to cholestasis - Canaliculi -\> canal of Hering -\> bile ducts - Can get cholestasis in hepatocytes, and bile plugs in canaliculi: can cause hepatocyte rupture and necrosis

Answer 63

- GALLSTONES: extrahepatic cholelithiasis - MALIGNANCY: biliary tree or pancreas

Answer 64

- **Acute large duct obstruction**: marked edema of portal tract stroma (white spaces) - Ductular reaction with admixed neutrophils at the _interface_ between portal tract and hepatocellular parenchyma (interface inflammation) - Portal tract: bile ducts - Interface: space b/t portal tract and hepatocytes

Answer 65

- **Ascending cholangitis**: ppl with large bile duct obstruction risk bacterial infections of static bile in the biliary tree 1. _Enteric orgs_ like coliforms and enterococci are common culprits (E. coli, Enterococcus) - HISTO: neutros in bile duct epithelial lining, and in lumen -\> acute inflammation attacking bile ducts - GROSS: purulent bile fills and distends bile ducts, and pt can get liver _abscess formation_ 1. Pockets of pus

Answer 66

- **Ascending bacterial cholangitis**: bile ductules (arrows) with luminal _acute inflammatory cells_ and hepatocytes with intracellular cholestasis - This is a a severe case -\> may be a little bile duct proliferation: neutros attacking them - SYMPTOMS: fever, chills, abdominal pain, jaundice - TX: relief of obstruction and AB's

Answer 67

- **End-stage biliary cirrhosis**: due to chronic biliary obstruction -\> note the nodularity (arrow) and bile staining - Ductular rxns from chronic biliary obstruction initiate periportal fibrosis, eventually leading to hepatic scarring and nodule formation, generating 2^o or obstructive biliary cirrhosis - Dilation of the duct system

Answer 68

- **Biliary cirrhosis**: unlike other forms of cirrhosis, nodules of liver cells in biliary cirrhosis are often not round, but irregular, like _jigsaw puzzle shapes_ 1. Haphazard - Compare to "other" forms of cirrhosis attached here -\> regenerative nodular: hepatitis C (more regular)

Answer 69

- **Chronic biliary obstruction**: retained bile salts cause enlargement of hepatocytes, and gives them a foamy appearance (large, similar to balloon degeneration) - Cholestatic features: 1. Feathery _degeneration of periportal hepatocytes_ 2. Cytoplasmic swelling, often w/_Mallory-Denk_ bodies (differ from those in alcohol-induced liver disease and non-alcoholic fatty liver disease by periportal predominance), and 3. Formation of _bile infarcts_ - Bile duct proliferation

Answer 70

- **Chronic biliary obstruction**: bile plug with necrosis (aka, bile infarct) - Necrosis: may just see hepatocyte surrounded by inflammation -\> macros coming in to clean up (can be very subtle) - Cholestatic features: 1. Feathery _degeneration of periportal hepatocytes_ 2. Cytoplasmic swelling, often w/_Mallory-Denk bodies_ (differ from those in alcohol-induced liver disease and non-alcoholic fatty liver disease by periportal predominance), and 3. Retained bile salts cause enlargement of, and give _foamy appearance_ to, hepatocytes

Answer 71

- **Cholestasis of sepsis**: most often in response to circulating microbial products (ducts, and not just canaliculi) - Most common form is _canalicular cholestasis_: bile plugs within predominantly centrilobular canaliculi - DUCTULAR CHOLESTASIS: ominous 1. Dilated canals of Hering; bile ductules at the interface of portal tracts and parenchyma also dilated 2. Contain obvious BILE PLUGS (front image) 3. Not a typical feature of biliary obstruction, but _septic shock_

Answer 72

- **Primary hepatolithiasis**: intrahepatic gallstone formation that leads to: 1. Repeated bouts of ascending cholangitis, 2. Progressive _inflammatory destruction_ of hepatic parenchyma, and 3. Predisposes to biliary neoplasia - FRONT IMAGE: atrophic right hepatic lobe with characteristic findings -\> markedly _dilated, distorted bile ducts_ containing large pigment stones + broad areas of collapsed liver parenchyma

Answer 73

- **Neonatal cholestasis**: conjugated bilirubin -\> should evoke search for recognizable toxic, metabolic, and/or infectious liver disease - BILIARY ATRESIA: major cause - NEONATAL HEPATITIS: variety of disorders causing conjugated hyperbilirubinemia 1. Lobular disarray 2. Apoptosis and necrosis 3. Multinucleated giant hepatocytes

Answer 74

- **Biliary atresia** (left): complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3 months of life - Salient features include: _inflammation & fibrosing stricture_ of the hepatic or common bile ducts - NOTE: normal bile duct on the right

Answer 75

- Not uncommon - PSC: ulcerative colitis, onion-skinning - KNOW THIS TABLE

Answer 76

- Primary biliary cirrhosis (**PBC**) - Autoimmune disease - Characterized by nonsuppurative, inflammatory destruction of _small and medium-sized intrahepatic_ bile ducts - Bile duct proliferation with inflammation all around it, but not going too far into hepatic parenchyma

Answer 77

- **Primary biliary cirrhosis** (**PBC**): lymphocytic inflammation and damage to a medium-sized bile duct in a portal tract (long arrow) - Poorly-formed GRANULOMA on the right side of the bile duct (curved arrow) - With inflammatory damage to the bile ducts, further flow of bile fluid distal to the damaged bile duct is impeded, resulting is _cholestasis_ and damage to hepatocytes

Answer 78

- **Primary biliary cirrhosis** (**PBC**): portal fibrosis with eventual development of cirrhosis in untreated cases is the natural course of the disease - Trichrome stain shows _concentric collagen fibrosis_ in a portal tract 1. Lympho inflam and damage to a medium-sized bile duct in a portal tract + poorly-formed granuloma on R side of bile duct

Answer 79

- **Primary biliary cirrhosis** (**PBC**): compensatory bile _ductular proliferation_ (long arrow) in portal tracts proximal to obstructed regions - Bile ductules: small-caliber ducts with cuboidal to flattened epithelium, often with collapsed lumima - Presence of multiple bile ductules in the periphery of a portal is a _telltale sign of distal bile duct damage_ in the biliary tree

Answer 80

- **Primary biliary cirrhosis** (**PBC**): extent and geography of _reactive bile ductular proliferation_ can be highlighted by immunostaining for **CK-7** b/c normal bile ducts are positive for this antigen - Note the absence of any medium-sized bile ducts inside the portal tract, and a rather brisk bile ductular proliferation at the portal border - Destruction of normal bile ducts in portal tract, and compensatory INC of bile ducts on the outside

Answer 81

- Regenerative hepatic nodule surrounded by bridging fibrosis - In this case, **primary biliary cirrhosis**: with progressive hepatocyte damage and fibrosis, portal-portal bridging fibrosis and frank cirrhosis develop - Fibrosis is "bridging," connecting the different portal tracts

Answer 82

- **Primary sclerosing cholangitis**: characteristic beading on radiographs - PSC is characterized by inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts with _dilation of preserved segments_

Answer 83

- **Primary sclerosing cholangitis**: culminates in biliary cirrhosis much like that seen with chronic obstruction and primary biliary cirrhosis - LARGE DUCT inflammation: _acute, neutrophilic infiltration_ of the epithelium superimposed on a chronic inflammation - SMALL DUCT: _little inflammation_ and a striking circumferential “_onion skin_” fibrosis around atrophic duct lumen, with eventual obliteration - Biliary intraepithelial neoplasia may develop and cholangiocarcinoma -\> usually w/fatal outcomes

Answer 84

- **Primary sclerosing cholangitis**: degenerating bile duct with “onion skin” fibrosis - Cholestasis - Biliary cirrhosis

Answer 85

- Choledochal cysts - Fibropolycystic disease - Congenital hepatic fibrosis

Answer 86

- **Choledochal cyst**: congenital dilation of common bile duct - PRESENTATION: kids _before age 10_ with jaundice and/or recurrent abdominal pain, and symptoms typical of biliary colic 1. _F_:M ratio 3:1-4:1 - Occur in conjunction w/cystic dilation of intra-hepatic biliary tree (Caroli disease) in some cases - Predispose to stone formation, stenosis/stricture, pancreatitis, and _obstructive biliary complications_ within the liver 1. In older pts, risk of bile duct carcinoma is elevated

Answer 87

- **Von Meyenburg complexes**: bile duct hamartoma always associated with portal tracts - Dilated and irregularly shaped bile ducts in fibrous background stroma - _Fibropolycystic disease_ of liver: heterogeneous group of lesions in which the primary abnormalities are _congenital malformations of the biliary tree_ 1. INC risk for cholangiocarcinoma - Can be confused with neoplasms, so often sent to pathology

Answer 88

- Single, or multiple (front), intra- or extrahepatic (i.e., along bile tract, or in liver) **biliary cysts**: when present in isolation, these may be symptomatic due to ascending cholangitis 1. Caroli disease - CAROLI SYNDROME (front): when biliary cysts occur along w/congenital hepatic fibrosis 1. Ducts may be cystically dilated, but true cysts are also present -\> may be intrahepatic cysts or choledochal cysts - _Fibropolycystic disease_ of liver: heterogeneous group of lesions in which the primary abnormalities are congenital malformations of the biliary tree 1. INC risk for cholangiocarcinoma

Answer 89

- **Congenital hepatic fibrosis**: portal tracts are enlarged by irregular, broad bands of collagenous tissue, forming septa that divide the liver into irregular islands - _Auto recessive_: linked w/muts in **PKHD1 gene** on chrom 6, leading to ductal plate malformation of intralobular bile ducts - _Not truly cirrhotic_, despite serpiginous scarring separating the hepatic parenchyma, BUT may still face complications of portal HTN, particularly _bleeding varices_ 1. Looks like von Meyenburg histologically, but V-M will NOT get these manifestations

Answer 90

- **Congenital hepatic fibrosis**: variable numbers of abnormally shaped bile ducts are embedded in the fibrous tissue, although they remain in continuity with the biliary tree

Answer 91

- **Budd-Chiari Syndrome**: portal HTN due to thrombosis of hepatic veins - Severe centrilobular congestion/necrosis, progressing to centrilobular fibrosis (hard to see necrosis in front image b/c acute, and inflam hasn't moved in yet) - Acute: can be fatal - MANIFESTATIONS: hepatomegaly, abdominal pain, ascites - CAUSES: polycythemia vera/myeloproliferative diseases, pregnancy, oral contraceptives (OC), abdominal cancer (esp. in the liver)

Answer 92

- Preeclampsia and eclampsia - Acute fatty liver of pregnancy - Intrahepatic cholestasis of pregnancy

Answer 93

- Affects 3-5% of pregnancies, & characterized by: 1. Maternal HTN, 2. Proteinuria, 3. Peripheral edema, and 4. Coagulation abnormalities - Subclinical hepatic disease may be primary manifestation, as part of _HELLP syndrome_ (need some trigger): 1. Hemolysis, 2. Elevated l iver enzymes, and 3. Low platelets - When hyperreflexia and convulsions occur, called _eclampsia_ and may be life-threatening - Can be post-partum

Answer 94

- **Preeclampsia**: periportal sinusoids contain _fibrin deposits_ associated with hemorrhage into SPACE of DISSE - Can lead to periportal hepatocellular _coagulative necrosis_ (see attached image)

Answer 95

- **Eclampsia**: blood under pressure may coalesce and expand to form a _hepatic hematoma_ - Dissection of blood under Glisson capsule may lead to catastrophic hepatic _rupture_ in eclampsia 1. Medical emergency

Answer 96

- Presents with a _spectrum of disorders_ ranging from subclinical or modest hepatic dysfunction (evidenced by elevated serum aminotransferase levels) to hepatic failure, coma, and death - Rare, usually in the _3rd trimester_, and most are mild - _Mito dysfunction_ (in BABY! Effects mother, woah) thought to play a role - Termination of pregnancy is primary treatment

Answer 97

- **Acute fatty liver** of pregnancy: microvesicular _steatosis_ in zones 2 or 3 (vacuoles may be very sm) - Also marked _ballooning of hepatocytes_ and macrovesicular fat - In severe cases, hepatocyte dropout, reticulin collapse, portal tract inflammation

Answer 98

- **Intrahepatic cholestasis of pregnancy**: 2nd leading cause of gestational jaundice (after viral hepatitis) -\> usually occurs _late in pregnancy_ - Estrogenic hormones may INH hepatocellular bile secretory activity - Mother at-risk for gallstones, malabsorption - Associated with higher incidence of _fetal distress, stillbirths, prematurity_ - SYMPTOMS: pruritis in third trimester, dark urine, light stools, jaundice - LABORATORY: some may have _elevated serum bilirubin_ (\< 5 mg/dl), usually conjugated; mildly elevated alkaline phosphatase

Answer 99

- **Gaucher disease**: genetic metabolic disorder in which _glucocerebroside_ (a sphingolipid, also known as, glucosylceramide) accumulates in cells and certain organs - Most common lysosomal storage disease - A few types, but _type 1_ most common - Enlarged liver and spleen -\> if bone marrow involved, trilineage decrease - CRINKLED PAPER APPEARANCE (tissue paper)

Answer 100

- _Normal liver_: reticular fibers black with silver, and nuclei red with nuclear fast red 1. Hepatocyte plates just 1-2 cells; pattern of reticulin can show you regenerative nodules and parenchymal collapse - Well-differentiated HCC will lose reticulin (see attached image: malignant cells have lost reticulin)

Answer 101

- Viral hepatitis, - Nonalcoholic fatty liver disease (NAFLD), - Alcoholic liver disease, and - Hepatocellular carcinoma (HCC) - Hepatic damage also occurs 2^o to some of the most common diseases in humans, like heart failure, disseminated cancer, and extrahepatic infections - The liver has a _massive reserve_ and has to have massive hepatocyte loss to see clinical change, in addition, the liver has the _ability to repair itself_, even at the fibrotic stage 1. REMEMBER: you have to destroy a lot of the liver to see changes in function, like diminished coagulation factors

Answer 102

- Healthy - Fatty: note the differences b/t normal and fatty liver attached here too - Cirrhosis - NOTE: hepatocytes can undergo a # of degenerative, but potentially reversible changes, like accumulation of fat (steatosis) and bilirubin (cholestasis)

Answer 103

- Fatty liver = steatosis

Answer 104

- Bilirubin = cholestasis

Answer 105

- **Hepatocyte necrosis**: osmotic regulation -\> fluid flows into the cell, which swells and ruptures - Macros clean up - Predominant mode of death is ischemic/hypoxic injury and a significant part of the response to oxidative stress - _Spotty necrosis_: normal liver cells surrounding group of macros cleaning up dead hepatocytes (not going to see confluent necrosis often b/c no reason to biopsy these pts)

Answer 106

- **Hepatocyte apoptosis**: active form of “programmed” cell death resulting in: 1. Hepatocyte shrinkage, 2. Nuclear chromatin condensation (pyknosis), 3. Fragmentation (karyorrhexis), and 4. Cellular fragmentation into acidophilic apoptotic bodies (aka, **Councilman bodies**; acidophil bodies) - Eosinophilic

Answer 107

- **Confluent necrosis**: widespread parenchymal loss with loss of reticular structures b/t hepatocytes - Zones matter - HISTO: cellular debris, macros, and remnants of the reticulin meshwork

Answer 108

- **Bridging necrosis**: zone that may link central veins to portal tracts or bridge adjacent portal tracts - Areas of necrosis starting to connect BEFORE you get to confluent necrosis - In some cases, there is scar regression

Answer 109

- Primarily via _mitotic replication of hepatocytes_ adjacent to those that have died, even when there is significant confluent necrosis - Hepatocytes almost _stem cell-like_ in their ability to continue to replicate even in the setting of years of chronic injury, and thus stem cell replenishment is usually not a significant part of parenchymal repair

Answer 110

- **Stellate cell**: in its quiescent form, it is a lipid (_vitamin A_) storing cell, but in several forms of acute and chronic injury, these can become activated and are converted into highly _fibrogenic myofibroblasts_ - When activated, they are a major player in fibrosis and scarring (aka, cells of Ito)

Answer 111

- Kupffer cell activation leads to secretion of multiple cytokines 1. _PDGF and TNF_ activate stellate cells - Contraction of activated stellate cells is stimulated by _endothelin-1_ (ET-1) - Fibrosis is stimulated by **TGF-β** - Chemotaxis of activated stellate cells to areas of injury is promoted by PDGF and _monocyte chemotactic protein-1_ (MCP-1)

Answer 112

- **Liver cirrhosis**: zones of parenchymal loss transform into dense fibrous septa -\> combo of the _collapse of underlying reticulin_ where lg swaths of hepatocytes have irrevocably disappeared and hepatic _stellate cells_ have been activated - Eventually, these fibrous septa _encircle surviving, regenerating hepatocytes_ in the late stages of chronic liver diseases that give rise to diffuse scarring described as cirrhosis - Looks different than biliary cirrhosis, which has more of a jigsaw look - This example is likely from something like Hep C

Answer 113

- Innate AND adaptive both involved - Ag's on APC's (incl. Kupffer and dendritic cells) presented to lymphos and TLR's detect host molecules/infections 1. Elaboration of pro-inflam cytokines that recruit inflam cells, and cause hepatocyte injury, vascular disturbances, promote scarring, and perhaps even malignant transformation - Adaptive immunity plays an even more critical role in viral hepatitis 1. Ag-specific CD8+ T-cells involved in eradication of Hep B and C, and 1^o causes of chronic viral hep, largely via elim of infected hepatocytes - Lymphos play destructive role, but also help induce local hepatocyte replication through secretion of cytokines

Answer 114

- _Zone 3_: this zone is very susceptible to anoxic, toxic and nutritional injury

Answer 115

- **Acute hepatic necrosis**: portal areas show inflam, most likely related to preexisting alcoholic liver disease; hepatocytes mostly viable, but an edge the necrotic zone is apparent (arrows) - Attached image: here the zonal necrosis is present around three central veins (V), while hepatocytes near portal areas (P) remain viable (massive acute necrosis) - Drugs are big players here

Answer 116

- **Acute** (sudden and massive) **hepatic necrosis**: liver is small, bile-stained, soft, and congested - Hepatocellular necrosis caused by acetaminophen overdose - IMAGE: zonal necrosis present around central vein (arrow/zone 3), while hepatocytes near portal areas (asterisk) remain viable

Answer 117

- **Diffuse microvesicular steatosis**: diffuse poisoning of liver cells w/o obvious cell death and parenchymal collapse - Not much known regarding pathogenesis of microvesicular steatosis, but primary defect could be a mitochondrial lesion, and _INH of the mitochondrial beta oxidation of fatty acids_ has been the most frequently implicated defect - EXAMPLES: fatty liver of pregnancy, idiosyncratic reactions to toxins, but now known to be seen in a large variety of diseases

Answer 118

- BLUE: microvesicular - GREEN: macrovesicular - Typically a mixture of micro- and macro

Answer 119

- **Chronic liver failure**: depressed areas of dense scar separating bulging regenerative nodules over the liver surface - Years/decades of insidious, progressive injury - CAUSES: chronic Hep B/C, non-alcoholic fatty liver disease, and alcoholic liver disease - Liver failure in chronic liver disease is most often associated with cirrhosis 1. While cirrhosis implies presence of severe chronic disease, it is _not a specific diagnosis_ and it lacks clear prognostic implications - Cirrhosis diffuse and is comprised of regenerating parenchymal nodules surrounded by dense bands of scar - A lot of changes in the liver are not specific: _need to have the clinical information too_

Answer 120

- **Regression of fibrosis**: does occur, even in fully established cirrhosis; this is another reason why cirrhosis should not be automatically equated with end stage disease - Scars can become thinner, more densely compacted, eventually fragment -\> _fibrous septa break apart, and adjacent nodules of regenerating parenchyma coalesce into larger islands_ - IMAGE: alcoholic cirrhosis in an active drinker (A) and following long-term abstinence (B). A, Thick bands of collagen separate rounded cirrhotic nodules. B, After a year of abstinence, most scars are gone. (Masson trichrome stain)

Answer 121

- **Hep B ground glass hepatocytes** - Attached image is typically used for Hep B and C - _Mononuclear infiltrate around portal tract_: hepatitis -\> don’t forget this - Can get balloon degeneration and spotty necrosis

Answer 122

- **Balloon degeneration**: can see this with hepatitis

Answer 123

And this staging system for chronic hepatitis. F0 no fibrosis F1 portal fibrosis w/o septa F2 portal fibrosis with few septa F3 numerous septa w/o cirrhosis F4 cirrhosis Good job!

Answer 124

- **Autoimmune hepatitis**: chronic, progressive hepatitis w/all the features of autoimmune diseases in general: 1. Genetic predisposition 2. Association w/other autoimmune diseases 3. Presence of autoantibodies, and 4. Therapeutic response to immunosuppression - PLASMA CELLS are prominent and characteristic component - INTERFACE (leaking out of portal tract, basically) hepatitis with plasma cells

Gupta - Pathology Flashcards

(148 cards)