Case workups: "Transaminitis" and such as a serum ASMA level of 1:640 by IFA is not enough evidence to diagnose autoimmune hepatitis, being only serum chemistry and serologigical lines of evidence. Many lines of evidence must be considered in order to arrive at a working or presumptive diagnosis and later and with more evidence, a final diagnosis. Biopsies are one very strong line of evidence when properly interpreted, usually in light of the knowledge of status of several other lines of evidence.
Liver biopsy "heads up":
- young patient & "bad" biopsy features: think Wilson's disease and AIH (document a normal serum copper level) [LMC-06-8934] & possibly cardiac sclerosis [L09-338] in a congenital heart patient.
- abnormal liver or LFT history and biopsy looks "normal":
- think of (a) non-cirrhotic idiopathic extrahepatic "increased flow" portal hypertension (look for peripheralized portal triad venules & rule out splenomegally) and (b) look for evidence of congestion due to any etiology that will raise inferior vena caval pressure (tricuspid valve incompetence may give a pulsatile U/S flow pattern in the portal vein while constant congestion likely won't [L12-2959]).
- Look carefully for even rare acidophil bodies and/or some hepatocyte swelling [L09-1613].
- If is histologically normal (and an adequate study so that at least 5 portal tracts are seen), our report can assure against the presence of a number of causes of liver disease [L09-541].
micronodular, miliary or microscopic:
Caroli's nodular fibro-polycystic liver [LMC-00-4308]
bean-sized or larger (macroscopic):
nodular hyperplasia (FNH)
fatty change (can also occurr in adenoma, FNH,
(hepatocellular carcinoma...HCC) [need to detail
the size, grade, mitotic rate, and margins...LMC-01-6453].
malignant melanoma [LMC-02-5801].
TUMORS & ABNORMALITIES:
uncertain biological behavior:
- gallbladder (GB)16 disease & cholecystodynia causes: Murphy's sign by physical exam is when the examining hand is pressed gently beneath the right subcostal margin at the time of respiratory expiration & then causeing pain there upon inspiration, while sonographic Murphy's sign is pain elicited as the sonographic probe presses over the GB. Something similar is reproduction of the patient's pain complaint when CCK is injected during the HIDA scan. The cystic duct node is sometimes within the hepatobiliary triangle (cystohepatic triangle; Calot triangle) and then called "Calot or Calot's node (or Lund's node) [L11-4284].
- cholecystitis without stones:
- incidental mucosal dysplasia or malignancy, see below.
- cholelithiasis (presence of or imaging history of stones, grit, sludge) and cholecystitis (acute, subacute, chronic inflammation). Any of these agents might be "seen" on ultrasound & not be appreciable in the grossing room exam. The muscular layer in routinely 10% NBF fixed GB is about 0.2 MM & clearly thick when over 0.4 MM [L09-3908].
- standard chronic:
- chronic: with stones; or without (acalculous...may see thickly inspissated bile) stones; may include
extramuscular liposclerosis or scleredema thickening.
- subacute: eosinophiles ; extramuscular stromo-vascular thickening.
- acute: suppurative, necrotizing, or gangrenous.
- xanthogranulomatous cholecystitis: thick & with visible yellowish histiocytic zones.
- ***hyalinizing cholecystitis or cholecystopathy: non-thickened paucicellular fibrous GB walls (about a 1.6% of GBs). Remarkable percentage of occult cancer in these cases22!
- calcified gallbladder (a type of potentially clinically palpable "Courvoisier gallbladder")...porcelain
- cholelithiasis limited to A/R sinuses: when the GB is involved by Rokitansky-Aschoff sinusosis (below), those diverticulae can become filled with calculi, with or without complicating inflammation [L11-14615].
- cholecystopathy or cholecystosis (chronic acalculous gallbladder disease; pericholecystitis21):
advances in radiology with ultrasound and nuclear medicine HIDA scans have advanced the knowledge of GB disease greatly since 1980. Therefore, a pathologist can focus the pathology gross & micro exam greatly by checking any readily available preoperative imaging studies during the prior year.
- surgeon removed the stones: the GB comes to the lab with some sort of opening & the operative note will never state that the surgeon removed the stones to show to the family [L09-3832]; or,
- stones were spontaneously passed: in the interval between imaging demonstration of small stones, the patient can pass them unbeknownst to anyone [L09-3832].
- preop imaging showed a lesion: but, lesion (such as polyp) not found, yet (1) GB has inflamation [L12-1016] vs. (2) does not have inflamation.
- sludge was demonstrated preoperatively by imaging [L11-14538].
- abnormal kinetic function IS demonstrated: (decreased or increased ejection fraction by HIDA scan) & usually little or no histological chronic inflammation but may see A-R sinuses and some muscular thickening = "dyskinetic cholecystopathy" [L09-470] which may take years to form and less likely when young patient & lesser sum of dyskinetic years [L09-2497]. Hypokinesis is sually assumed to be due to "cystic duct syndrome" wherein the duct constricts rather than relaxing when the GB squeezes; hyperkinesis with pain reproduction may simply squeeze too fast for the duct to accomodate [L12-5421; L13-266] & reproduce the pain, hyperkinetic cholecystopathy. But couldn't plicaytions or deposits such amyloidosis or other deposits or diabetic neuropathy effects cause dyskinesia?
- abnormal function IS NOT demonstrated (HIDA scan normal but not really high ejection fraction) & no histological chronic inflammation [L08-13447] but may see A-R sinuses and some muscular thickening. This might mean that there is distal common bile duct spincter of Oddi spasm if the GB ejection was normal but contents don't follow into duodenum.
- everything histologically & kinetically normal: with good & high HIDA ejection fraction...but (1) not too high & (2) no pain reproduction = doubtful cholecystopathy. Surgery may have found another etiology for pain and the GB incidentally removed because did not appear to be perfectly normal [L09-596]. Really concentrated, thick bile might result in poor function in vivo even though CCK test normal [L09-2253 "thick bile dyskinesia"]. Otherwise, being all normal, one might warn surgeon, et. al., in your report to think of hereditary angioneurotic edema if episodes of N&V are prominent (HAE) [L12-3454], cholecystodenia-like fatty-liver-associated abdominal pain, non-cutaneus "shingles" (VZV) neuropathy, or acute intermittent porphyria (AIP) [L09-266]. Or, surgeon might have even repaired (without alerting the pathologist) such an occult cause of pain as some occult abdominal wall or internal incarcerated hernia [L09-3762] or taken down pericholecystic adhesions between such as omentum, stomach, or colon [L12-1168].
- hyperplastic cholecystopathy (radiologically, hypertrophic or "hyperplastic cholecystosis"):
- Rokitansky-Aschoff (or Aschoff-Rokitansky) sinusosis: the GB wall may seem grossly unremarkable or be distorted by grossly visible, multiple A/R sinuses (GB diverticulosis) to the point that at least some of the GB wall seems thickened, even prominently thickened, even with one or more intra-diverticular calculi.
- adenosis: incidental focal mucosal adenosis [L08-11597; L09-470].
- adenomyoma: (usually in fundus & has increased smooth muscle) admixture
of benign A-R-sinus epithelium & smooth
muscle [LMC-05-6849] forming a plaque; can centrally ulcerate [L09-1778].
- sinusosis: hyperplasia of intramural A-R sinuses without (1) grossly easily discernible mural thickening or (2) significant smooth muscle participation [L13-2300, with one intra-AR calculus]. It can be focal, multifocal, and from mild to extensive. Sinusosis & adenomyosis CAN look infiltrative & even be in perineural spaces23; can give a positive PET scan when there is much inflamation24; has very low Ki67 proliferation and negative p53 [L13-2300].
- adenomyomatosis (adenomyosis): from mural grossly "normal' to mural thickening and very prominent Aschoff-Rokitansky...Rokitansky-Aschoff...sinuses [A-R sinuses]) [L07-324; L07-1966]; A-R "sinus" formation with patterns from pseudoinfiltrative (chlocystitis glandularis proliferans) to mucosal herniations or diverticuli prominent enough to be seen by preoperative ultrasound as a "comet tail defect" when stones in sinuses & "pearl necklace gallbladder" by oral cholecystogram (...a reflection of chronic cholecystitis and GB dyskinetic function. The sinuses can contain calculi; ruptures may be the etiology of xanthogranulomatous cholecystitis. Sinusosis & adenomyosis CAN look infiltrative & even be in perineural spaces23; can give a positive PET scan when there is much inflamation24; has very low Ki67 proliferation and negative p53 [L13-2300].
- segmental adenomyomatosis.
- diffuse adenomyomatosis.
- metaplasia: pyloric or mucinous; intestinal (to include Paneth).
- papillary hyperplasia: highly velvety mucosa due to mucosal elongations (can be focal, segmental, diffuse).
- adhesive cholecystopathy: these cases can only be appreciated by the pathologist if he/she reads the surgeon's operative note. They may hepatocholecystic or connected to many other different areas/organs.
- pericholecystitis/pericholecystic metastatic disease: gallbladder removed from within or on the edge of other pathology, such as perforated ulcer[L12-2489].
- shape abnormality: Phrygian cap (of distal body...area bulges or protrudes & folds slightly like a broad diverticulum due to a mural/mucosal fold).
- adenomatous change: unifocal or multifocal,
incidental truly adenomatous change of mucosa [LMC-02-3532; L12-15511].
- mucosal papilloma.
- polyps: cholesterolosis
polyps (range from 1-5mm); inflamatory polyps; metaplastic polyps [L12-9976]; villous papilloma; adenoma; granular cell tumor; adenomyoma..
- mucosal lymphoid hyperplasia.
- Mucocele: cystic duct obstruction so complete & chronic that GB distended with mucous.
- calcification: murally calcified porcelain gallbladder ("Courvoisier gallbladder"); sometimes focal or zonal [L13-2924].
- heterotopia (ectopic, ectopia, choristoma): normal tissue in abnormal location...gastric, pancreatic nodule [LMC-07-361], hepatic, thyroid,
- ciliated foregut cyst.
- cystic duct lymph node enlarged: this may be due to nonspecific hyperplasia, sarcoid, lymhoma, metastatic carcinoma or oleogranulomatous lympadenopathy [L09-3729].
malignancy (all biliary adenocarcinomas arise via a "field effect"12):
- carcinoid: a
3 mm incidental (surgery & pathologist) cystic
duct carcinoid in 79 y/o female [LMC-02-2548].
- gallbladder or cystic duct adenocarcinoma: 8
mm in distal cystic duct arising in accessory glandular "saccules
of Beale" in 50 y/o male[LMC-98-956]; resect and radiate13,14. Found (several times a year in our practice) in routine cholecystectomy specimens [L12-11982].
- psuedocarcinoma "picture": sinusosis & adenomyosis CAN look infiltrative & even be in perineural spaces23; can give a positive PET scan when there is much inflamation24; has very low Ki67 proliferation and negative p53 [L13-2300].
- common bile duct adenocarcinoma:
- proximal = Klatskin tumor [T-06-182]
- ampulla of Vater
carcinoid: some can be pigmented (1.1 cm melanin-containing carcinoid of common duct in 48
y/o [S-02-3904] husband of our employee).
- adenoendocrine (mixed exocrine endocrine; amphicrine; adenocarcinoid) carcinoma: worse actor than pure neuroendocrine tumor.
Tumors composed of a mixture of endocrine and exocrine cells have been recognized especially in the digestive
- pure cholangiocarcinoma:
- cholangio with intrahepatic nodules vs. met. adenoca. [CN09-12].
patterns or markers:
- biopsy processing & stains
lobule: [...especially in a younger person [L07-8934], liver disease without fairly easy diagnosis: think of Wilson's disease (diagnose with Kayser-Fleisher
ring... a rusty brown ring around the cornea of the eye that can best be viewed using an ophthalmologist’s slit lamp; and by a heavy metal
analysis of serum specimen for "serum free copper level" or quantitative tissue copper level from liver biopsy, and by finding low levels of serum
ceruloplasmin (< 20 mg/dl)]. And, for a patient wanting to track therpeutic response, plug values for serum copper, ceruloplasmin, & non-ceruloplasmin [free]
copper using the The Wilson's Disease Patient Lab Tracker.
body: necrotic dense shrunken hepatocyte
with pyknotic nucleus or no nucleus; were
called a Councilman body in days of yellow
fever (and contained tiny fat droplets
and ceroid pigment). Biopsy done for abnormal LFTs & not much change, look hard for these [L09-1613].
- atrophic hepatocytes: centrilobular sinusoidal dilation due to increased systemic venous pressure [L08-13713].
body: fragment of an acidophile body.
an FNA cell smear are strongly indicative
anisonucleosis: notable nuclear
and cell size variation.
dysplasia: more pronounced than
(hepatocytes as groups):
in the cell:
- ballooning degeneration: swollen hepatocytes which are relatively pale and are edematous
(viropathic ballooning of viral hepatitis), have ground-glass change (see below), feathery degeneration
when due to cholestasis, or "hydropic" or "foamy cell" change (which can be very spotty & subtle & "callable" at that mild stage when ALT only a couple hundred & no other real findings [L09-1613]) when due to other injuring or damaging insults. Fatty foamy change may look very similar.
immunodeficiency syndrome (oncocytes)
(alcoholic or hep. B or C...oncocytes)
cholestatic hepatitis or drug hepatopathy
(induction cells): the endoplasmic
reticulum is hyperplastic to amplify
enzymes available to deal with
the steroids/drugs...can look a
little like Golgi enhancement [LMC-04-4500]
storage disease, type IV
ca. (fibrinogen or hep. B virus)
familial myoclonic epilepsy (Lafora
hepatitis B cells
- hemochromatosis: it is clearly possible to have genetic hemochromatosis, yet liver biopsies be only slightly positive (low/mild iron burden) in the
hemochromatosis pattern of hepatocyte cytoplasmic positivity (rather than predominately in macrophages.
ester storage disease
of drug-induced induction cells
storage disease (fibrinogen)
(glycolipid, glycoproteins, other
focal hepatocellular glycogen deposition
syndrome (diabetic steatohepatosis): childhood diabetic dwarfism with hepatosplenomegally.
bodies: see with drugs (amiodarone) and alcoholic, etc., and high-light with IHC for CK8 or ubiquitin.
markers: ALT (SGPT);
ornithine carbamoyltransferase; sorbitol
dehydrogenase; LDH (liver ischemic necrosis
marker); albumin (produced solely in liver);
prothrombin time is functional marker of
cholestatic ballooning, see above.
cell change: fatty ballooning, see above.
change (poor cell membrane definition) of hepatocytes: alcoholic hepatitis.
infarct: alcoholic hepatitis; ascending
cholangitis in a cirrhotic [LMC-05-6894].
with bile...cholestatic jaundice:[LMC-04-4500...steroids].
- duct of Hering particularly dilated, to point of almost small bile lake (porto-lobular cholestasis) & some ductule proliferation chemotacting polys even barely into lobule...TPN-associated cholestasis [L07-3345].
congestion & maybe even evidence of thrombosis: acute
Budd-Chiari syndrome [LMC-02-23; FA08-157]
(classical presentation is of abd. pain,
ascites, fever, & splenomegally); chronic in a case of extramedullary hematopoiesis [LMC-04-11140].
increased right-sided systemic venous pressure (may cause U/S pattern of coarsened echotexture), see VOI,
below, gives dilation of central sinusoids
(due to hepatic vein, IVC, incompetent cardiac valves, right heart failure [L08-13713], constrictive
pericarditis...anything that increases venous
pressure from central vein into hepatic lobule [L12-2959]). A review of the hepatic ultrasound can (1) confirm correct portal flow direction and (2) detect pulsatile flow of incompetent tricuspid valve as the cause. BUT, appearing dilated can also be due to general hepaticytic atrophy due to portal vein or hepatic artery insuffciency18!
Some toxic or medication effect can cause a pre-pelosis like central dilation. AND, a cautery-biopsy thermal artifact can cause angioma-like dilations17 due to hot vapor bubbles irregularly
dissecting the sinusoids and
incompletely lined by reticulin and not lined by endothelium...and may even seem to contain some type of lumenal matter [L07-2170].
sinusoidal collagen or reticulin deposition in post
jejunoileal bypass for obesity: this also has
macrovesicular fatty & portal tracts & septae
may have polys & lymphs. When extramedullary hematopiesis induces increased hepatic blood flow, may get sinusoidal fibrosis [LMC-04-11140; L11-12010] which can lead to portal hypertension. Reticulin stain needed to ascertain.
- CBC peripheral blood smear:this may show atypical or even CLL-type lymphocytosis which may or may not [L07-1938] be appreciable in the liver
biopsy & may reflect current or waning EBV or CMV (which had caused "elevated LFTs".
EBV, HCV, CMV [LMC-77-2430;
LMC-79-2489; LMC-03-7591; LMC-03-8574; ?LMC-04-106],
inflammatory infiltrates: think of rickettsia-like
ca.: especially small cell lung ca. [LMC-84-3358/9;
cells: these sinusoidal cells in space
of Disse become prominent in hypervitaminosis
A and PBC4; if you can see
them (whether nuclei are pressed into stellate
shapes or not), it is "prominence" of
Ito cells.[LMC-97-4366; LMC-04-4500]
stain: if single or clusters of lining
cells contain positive, fine granules, this
is a sign of hepatocyte necrosis within the
past 6 months
cause venous outflow impairment...VOI):
above] (check for some type of hypercoagulable
syndrome) is appelation for more of an extrahepatic
or large caliber thrombosis..."veno-occlusive
disease" for smaller-vessel lesions. Many
cases have quite elevated alk phos & GGT
and some portal changes suggestive of chronic
bile duct disease9.
sinusoidal collagen deposition in post
jejunoileal bypass for obesity: this also
has macroves. fatty & portal tracts & septae
may have polys & lymphs.
tissue profile: watch out for amyloid deposits causing relatively acellular portal profile expansion and/or portal arteriolar enlargment [A11-13].
typically fairly small, in center of triad, and not
dilated. Banti's syndrome, in a broadest sense, is
any case of splenomegally not
due to (1) large caliber thrombosis of the hepatic
vein or (2) cirrhosis.
lesions:intraluminal vs. extraluminal
lesions; usually no change in liver
lesions: idiopathic portal hypertension...non-cirrhotic
portal hypertension (due to wide variety of
causes, one specific but poorly understood
cause being hepatoportal sclerosis [HPS]...increased reticulin sinusoidal fibrosis).
HPS is hard to diagnose on needle biopsy, but
you may note portal triad peripheralization of triad vein, thickening of portal venule, corrugation
of vein profile, dilation of vein profile,
or subdividing of vein profile as if a thrombus
was recanalized. When dilated & maybe complex,
the presence of terminal bile ductule lets
you know that you are looking at a portal triad.
As opposed to cirrhotic portal hypertension,
that due to HPS tends to retain plenty of parenchymal
functional reseerve; is apparently irreversible; check patient for thrombophilic hypercoagulation
(some think this may be part of the etiology).[S04-4874]
artery: being adjacent
to bile duct and/or as "naked arterioles" may
indicate ductopenia; look for amyloidal thickening [A11-13].
contain d-PAS positive granules, may reflect
hepatocyte necrosis within past 6 months
see sarcoid and fibrin-ring & other
photos & granuloma info
Dr. Yale Rosen's website.
lymphoid: heavy lymphoid, especially when forms lymphoid nodule (Poulsen lesion), brings up PBC5 & HCV.
cells: when seen, these bring to mind AIH or a mixed etiology with an autoimmune component. When serologies are negative, autoimmune features are not ruled out; but sero-negative AIH [L10-11828] can can be addressed by an analysis of the factors HERE.
eosinophiles: these bring to mind a drug reaction component.
bariatric post-bypass cases, see above; any time there is bile ductule proliferation; medication induced; ascending cholangitis; ascending pericholangitis [L06-2862].
if serological test becomes "negative" over
the years (as of 1/2002), one is considered to
have lifetime immunity if a positive antibody
response to vaccination was ever demonstrated.
lesion (portal lymphoid nodule...especially with biliary duct
in center) [LMC-03-3712; LMC-03-6375
USA cases are HCV-1, only 30% of which respond
to interferon (whereas 65-70% of HCV-other respond)
C blood tests work-up rationale
- HCV can present with elevated ALT, cryoglobulinemia, membranoproliferative glomerulonephritis, and PCT.
D (has to have hepatitis B with it)(HDV):
even be fulminant)
B19 (almost never jaundiced)
sclerosing cholangitis (PSC):
chronic cholestatic situation, mostly in chronic
ulcerative colitis patients
usually negative...no distinctive marker
there is the classical disease; and the small-duct
variant may be impossible to distinguish histologically
from PBC; may need to use ck7 and ck19 to hunt
sclerosing cholangitis: usually due
to lesions obstructing (or "low flow")
vascular flow to biliary tree [LMC-03-5668]
(spectrum)...(AJCP 114:705-711, 11/2000):
vs. biliary cells:
destructive cholangitis (florid duct lesion)...
serological: AMA titers
high in >90% [LMC-01-2794;
LMC-02-4906; LMC-02-5844] There
can be AMA negative PBC [LMC-03-4430]
elevation of alk. phos., elevated IgM
duct loss (50% or greater of portal tracts
lack ducts); may see Poulsen lesion19[L07-2104]; 80% of cases with small granulomas;
heavy portal cellularity and cells involve
duct epithelial interface...duct injury ("florid
duct lesion")...may need to use ck7
and ck19 to hunt residual cholangiocytes;
periportal hepatocytes may be swollen and
cholangitis [immunocholangitis; autoimmune
PBC but neg. AMA [S-04-4874; L08-3230]
can be apparent biliary changes within portal
chronic inflammation that is apparently just
part of the NASH process.
serological: high ANA;
sometimes p-ANCA pos.; neg. AMA;
may also have positive ASMA [L-04-10922; L06-2337]
ALT (SGOT) increase
destructive cholangitis; 70% with granulomas;
bile duct lesions and ductopenia; lower grade
fibrosis than PBC; may need to use ck7 and
ck19 to hunt residual cholangiocytes
overlap syndrome of
PBC & AIH (OLS...a hepatitic variant of
clinical: ; it is possible to have serological "overlap" with disproportionate or negative corresponding histological overlap [L08-3332]; overlap is in 20%
of patients with autoimmune liver disease5,
of 3 PBC features (pos. AMA, florid duct
lesion, AP 5x uln)
of 3 AIH features (pos. ASMA, severe
interface cellularity, ALT 5x uln, serum
IgG 2x uln)
serological: high ANA [homogeneous];
histology: ;45% with granulomas.
autoimmune hepatitis (AIH):
first described in 1950s as "lupoid hepatitis" because
had pos. ANA
insidious; rarely acute
elevation of serum IgG when pure etiology
many as 20% present (2005) without currently known & detectable auto
antibodies (ANA, ASMA, anti-LKM-1, p-ANCA) [LMC-04-6010].
- ASMA can be significantly elevated in other situations.
- at least 24 medications are implicated as drug-induced AIH.
1999 report, formula to calculate whether
(J. of Hepatology 31:929-938, 1999)
or middle-aged females
titers ASMA, or ANA,
or both [LMC-02-747]; ASMA (anti-SMA) & ANA (anti-nuclear antibody) can be negative but should have positive anti-SLA (soluble liver antigens), p-ANCA, and/or anti-ASGP-R (asialoglycoprotein rector).
ALT (SGOT) elevation; serum gamma globulins
piecemeal & confluent lobular injury; <10%
granulomas; portal plasma cells and eos.
microsomal antibody positive AIH (usually > 1:320) ; if not positive, then anti-LC1 (liver cytosolic protein type 1) should be positive (and/or anti-SLA and/or anti-GOR) but ANA & ASMA negative20.
in 1987 & common in southern Europe;
rare in northern Europe and USA
HLA DR4 common
aggressive, poorly responsive variety of
at young age, female, usually no other
auto-Abs except maybe low titer ANA (may
be "fine speckled"), often associated
with other autoimmune disorders
associated IgA deficiency, poor candidate
for liver transplant
- AIH type III:
- is AMA and SLA positive, maybe with ASMA but not ANA or LKM20.
- AIH type IV:
- is mostly children with high ASMA but negative for SLA or AMA20.
as in association with an episode of acute pancreatitis
where you see a few portal lymphocytes, eosinophiles,
and polys [LMC-03-3790]
(Tylenol) toxicity: central necrosis with prominently elevated ALT & LDH [FA-95-36;
tetracycline: microvessicular fatty liver.
[grading the injury].
- minocycline: "hepatitis", AIH & otherwise; as a tetracycline like med, possibly microvesicular fatty change [L07-8935].
- Lovastatin: hepatocellular injury.
ascending cholangitis: polys in biliary lumen or
epithelium (biliary tract infection)
ascending pericholangitis: polys in portal tracts
(abdominal infection...or inflammation...with lymphatic
spread up the portal lymphatics: from PID, UC, etc.) [LMC-05-6894]
or metabolic disease:
abscess (ameba hist. serology should be positive)
(obvious on iron stain): when significant numbers of hepatocytes have granular positivity...whether heavy or not (whether low or high iron load or not), genetic
hemochromatosis is possible, and the finding is grounds for genetic testing [L07-6489]. The serum iron profile is used to interpret the total body iron status.
Heavy metal analysis of quantitative iron in the liver biopsy can help (Mayo Clinic.
antitrypsin deficiency (visible with d-PAS stain...sometimes
H&E and trichrome...as round globules)[LMC-03-2385;
- NAFLD/NASH: fatty liver whether is macrovesicular or microvesicular or even so fine-calibre as to be "foamy degeneration
" (a nomenclature pigeon-hole implying "fat" & lumped in the broader category of ballooning degeneration of
hepatocytes (L-06-6796); "non-alcoholic fatty liver
disease "/"non-alcoholic steatohepatitis
fatty liver; NASH, a fatty liver which also has a little on-going injury
of liver cells...seen in people of normal weight as
well as overweight...needs management. If no evidence
of hepatocyte injury (no elevation of ALT & few
or no fine-granule-positive sinusoidal or portal macrophages)
= non-alcoholic steatohepatosis. Brunt
site and another
ratio usually <1.06
hypertension or cirrhosis workups ("portal venopathy"17):
associated: pretty obvious on biopsy.
- non-cirrhosis associated 8
(peripheralized triad venule and maybe zones of heaptocyte atrophy17):
causes increased pressure/obstruction: portal
venule problems which either (1) "restricted flow" (prehepatic, intrahepatic, or posthepatic) or (2)
"increased flow" due to noncirrhotic splenomegally or some type of aterio-portal shunt (likely to only
see peripheralized triad venule [LMC-07-389]). Increased flow due to extramedullary hematopoiesis causes sinusoidal fibrosis which leads then to restricted flow [L11-12010].
causes increased pressure/obstruction:
such as amyloidosis or fibrosis (HPS)[L-04-11140; L11-12010].
(central) causes increased pressure/obstruction: largely
cardiac failure or hepatocaval thrombosis which produce increased right-sided caval venous pressure [L12-2959].
discovery elevated liver function tests:
presents in coma:
(posted 2001; latest
addition 25 February 2013)
Ludwig & Batts,
Practical Liver Biopsy Interpretation, 2nd Ed., ASCP Press,
[Mayo Clinic pathologists] 1998.
LKM-Positive AIH in
the Western US: A Case Series, Scripps Clinic, A. J.
Gastroent. 95(11):3238-3241, 2000.
hepatitis Group Report: review of criteria for diagnosis
of autoimmune hepatitis, Journal of Hepatology 31:929-938,
Frank Mitros' web site...link
at top of this page
Pathology of the Liver,
4th Ed., 2002, MacSween, et. al.
Burke, MD, "Liver
function: test selection and interpretation of results", Clinics
In Laboratory Medicine, 22:377-390, 2002.(EBS's office)
Snover Dale C., "Liver
Pathology", morning workshop, 11th Annual "Seminar
in Pathology", Pittsburgh, April 28-May 2, 2004.
Roskams T, et. al., "Histopathology
of Portal Hypertension: a Practical Guideline", Histopathology
42:2-13; January 2003 (EBS's office).
Kakar S, et al, "Histologic
Changes mimicking biliary disease in liver biopsies with
venous outflow impairment", (Mayo Clinic), Modern Pathology
17(7):874-878, July 2004.
G. Lee's on-line liver pathology book
Stone JH, et. al.,
Human Monocytic Ehrlichiosis, JAMA 292(18):2263-2270, 10
- Rodger Haggitt consult re: cancer of saccules of Beale, 1998.
- Japanese J. of Surgery 19(6):691-698, 1989.
- Annals of Surgery 219(3):267-274, 1994.
- Japanese J. of Clin. Onc. 29(5): 252-255, 1999.
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