Common Non-neoplastic Abnormalities of  the Liver:     

-- Chronic hepatitis, **** active, HAI score = ****/18 (See scoring Synopsis below).

-- End stage liver disease with extensive micronodular cirrhosis, bile ductular proliferation and portal mononuclear inflammatory infiltrate.

Common Neoplastic Lesions of  the Liver:     

-- Hepatocellular adenoma with extensive severe steatosis, favor HNF-1-alpha-mutated subtype (see Note)

-- Focal nodular hyperplasia (3.8 cm). No carcinoma

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Clinical scenario:  56-year old  man with hep-C; abnornal LFTs.      

Liver, needle core biopsy: 

-- Chronic hepatitis, **** active, HAI score = ****/18 (See scoring Synopsis below).

-- No cholangitis, cholestasis, steatosis or dysplasia.

-- No significant hepatic fibrosis, fibrotic stage = **** out of 6.

Histologic Activity Index and  Fibrosis Scores

Ishak system

Portal inflammation and: ****/4

Periportal (interface) inflammation: ****/4

Lobular inflammation: ****/4

Confluent necrosis: ****/6.

Fibrosis or stage: ****/6

Note:  The histological findings are compatible with the patient's clinical history of type-C viral hepatitis.  These changes, however, are not pathognomonic and can be seen in hepatitis of other etiologies.  Clinical correlation is required.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  55-year old man, h/o hepatitis-C; eval for cirrhosis.        

Liver, random core biopsy: 

-- Chronic hepatitis, mild to moderately active (HAI = 6 out of 18), compatible with the patient's clinical history of type-C viral hepatitis (see Note)

-- A significantly increased number of portal and lobular eosinophils, etiology uncertain

-- No steatosis, cholestasis, granulomatous inflammation or dysplasia

-- Mild portal fibrosis, stage 1 out of 6.

Note: The constellation of mixed portal inflammatory infiltrates with focal lymphoid aggregate formation, interface hepatitis and lobular inflammation is compatible with the patient's clinical history of type-C viral hepatitis.  These findings, however, are not pathognomonic for hepatitis-C and can be seen in hepatitis of other etiologies.  The presence of a significant number of eosinophils is not a feature of chronic viral hepatitis.  Concurrent chemical injury (such as drug induced toxicity) as a concurrent component of the liver injury should be considered  

Editor's comment:

concurrent / co-existing compoents should be considered

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Clinical scenario:  55-year old woman with multiple liver nodules.      

Liver needle core biopsy: 

-- Multiple non-necrotizing epithelioid granulomas with multinucleated giant cells and focal polarizable crystals i n the granuloma consistent with chronic granulomatous hepatitis (see note)

-- No cholestasis, bile stasis, bile duct loss or definite granulomatous cholangiopathy

-- No significant fibrosis

Note:  Sections show several generous liver cores with adequate numbers of portal triads for evaluation. There are multiple non-necrotizing small, well formed epithelioid granulomas with multinucleated giant cells that distribute in both the lobules and portal tracts. Very mild portal and focally lobular mononuclear inflammatory infiltrates of lymphocytes and plasma cells are also noted. Occasional eosinophils are readily observed. Rare polarizable crystal material is identified invading the epithelioid granuloma. The main differential diagnoses include infection, sarcoidosis and drug inducted granulomatous inflammation. Several special stains for fungal organisms and mycobacteria are negative although this result cannot entirely exclude infection. Further clinical workup for sarcoidosis and possible drug hypersensitivity.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  56-year old man, liver cirrhosis of  unknown etiology       

Native liver (1460 grams), explant (total hepatectomy):

-- End stage liver disease with extensive micronodular cirrhosis, bile ductular proliferation and portal mononuclear inflammatory infiltrate.

-- Patchy paracellular cholestasis, confirmed by bile stain.

-- No granuloma, periductal fibrosis, dysplasia or carcinoma identified.

-- PAS-D stain reveals no intracytoplasmic hyaline globule.

-- Perl's stain reveals mild iron deposition in a periportal pattern, grade 1 out of 4.

-- Trichrome stain confirms the cirrhosis.

-- See microscopic description and comment..

Note: Although the micronodular cirrhosis, active fibrosis with bile ductular proliferation and mononuclear inflammatory infiltrate are compatible with the patient's clinical history of type-C viral hepatitis, these changes are not pathognomonic.  It is difficult to render a definitive etiological diagnosis. The micronodular cirrhosis pattern and absence of significant periductal fibrosis do not support PSC.  Relative preservation of centrilobular zone is not compatible with cirrhosis secondary to steatohepatitis.  Negative stain for intracytoplasmic hyaline globule can exclude alpha-1 antitrypsin deficiency as the underlying etiology.  Iron deposition can be seen in both end-stage liver disease and hemochromatosis

Editor's comment:

It is among the easiest to render a diagnosis of liver cirrhosis, but often among the most challenging to identify the underline etiology. Yet an etiologic diagnosis is important for post-transplantation follow-up and management of the patient. While it is difficult to identify the underlying cause, effort should be make to exclude these common and easily identifiable such as alpha-1 antitrypsin deficiency and hemochromatosis.

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Clinical scenario:  40-year old woman with a solitary liver mass.        

Liver, needle core biopsy:     

-- Mild lobular disarray and absence of portal tracts, most compatible with hepatocellular adenoma (see Note)

-- Patchy mixed macrovesicular and microvesicular steatosis (10% of liver parenchyma)

-- No metastatic carcinoma identified

Note: Sections show liver tissue without apparent portal triad.  There is lobular disarray and unpaired small arterioles. Patchy steatosis is also noted.  But cytological atypia is minimal in this biopsy. Absence of bile ductules (i.e. portal triads) is confirmed by immunohistochemical stain for CK7.  If there is a history of oral contraceptive use, and there is no significant liver fibrosis on imaging study, these findings are most compatible with hepatocellular adenoma although differentiation from well-differentiated hepatocellular carcinoma cannot be readily made histologically. Correlation with imaging studies and clinical history is recommended.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  40-year old woman with a solitary liver mass.        

Liver "mass",  excision:     

-- Hepatocellular adenoma with extensive severe steatosis, favor HNF-1-alpha-mutated subtype (see Note)

-- No peliosis hepatis, intratumoral hemorrhage or tumoral necrosis

-- The inked parenchymal resection margin is free of the tumor by at least 3 mm

-- No significant histologic abnormality in the non-neoplastic liver parenchyma

Note: The combined histologic and immunohistochemical findings support the diagnosis of a hepatocellular neoplasm. In the absence of background cirrhosis, cytological atypia, tumoral necrosis, vascular invasion, the findings are consistent with a hepatocellular adenoma. Prominent steatosis and absence of significant neutrophilic infiltrates or intratumoral hemorrhage favor a HNF-1 alpha-mutated subtype of hepatocellular adenoma. This subtype is predominantly seen in women with contraceptive usage, carries low risk for intratumoral hemorrhage and has the lowest rick for malignant transformation. Since the radiographic imaging studies reportedly have high sensitivity and specificity in distinguishing the inflammatory and HNF-1 Alpha-mutated subtypes.

Editor's comment:

With excisional specimen, a definitive diagnosis of hepatocellular adenoma can often be made. Since different subtypes of hepatocellular adenoma.carry different clinical risk and often are managed differently, it is advised to specify the subtype in the pathology report. When the subtyping becomes well adopted, it may not be necessary to comment on differential features of each subtype in the Note section.

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Clinical scenario:  16-year old boy with abdominal pain, weight loss and occasional diarrhea.      

Liver, needle core biopsy: 

-- Poorly differentiated carcinoma, present in four of eight biopsy cores, constituting approximately 10% of the biopsy with maximal contiguous tumor line length of 4 mm, most likely of pancreatobiliary origin (see Note).

-- No significant fibrosis, cholestasis or steatosis of the benign liver tissue.

Slides examined: 2 H&E; 8 IHC

CPT: 88307; 88342 x 8.

Note:  Immunohistochemical stains, with adequate controls, show tha the tumor cells are positive for CK19, Ca19.9, Muc1 but are negative for CK20, CDX2, TTF1, Hepar1 and arginase.  The combined histologic and immunohistochemical findings support the above diagnosis.

Editor's comment:

For a malignant neoplasm, type, degree of differentiation, extent (line length) should be included in the report. Although paragraphical format is less readable than short-list, it makes easier to dictate and transcribe..

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Clinical scenario:  16-year old boy with abdominal pain, weight loss and occasional diarrhea.      

Liver, right lobe, partial hepatectomy: 

-- Metastatic colorectal adenocarcinoma, moderately differentiated, two separate foci, 3.8 cm with 75% of tumor necrosis consistent with moderate response to chemoeduvant therapy, and 0.5 cm without necrosis, respectively.

-- The larger tumor focus involves an interlobar bile duct

-- No tumor thrombus, perineural invasion or invasion of portal, hepatic vein.

-- Parenchymal resection margin is free of tumor by 0.6 cm.

-- No significant fibrosis, steatosis or cholestasis of background liver.

Slides examined: 12 H&E

CPT: 883079

Editor's comment:

For a metastatic malignant neoplasm, the histologic type, the primary source, degree of differentiation, extent (line length) should be included in the report.

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Clinical scenario:  39-year old man with portal hypertension.         

Liver, left lobe, needle core biopsy and wedge resection: 

-- Nodular regenerative hyperplasia, etiology uncertain (see Note).

Note: The wedge resection specimen shows multiple vaguely-defined hyerpcellular nodules measuring 1-3 mm, centered around portal triads, and diffusely involving all sections.  There is centrilobular congestion and mild sinusoid dilatation. There is no steatosis, cholestasis or lobular inflammation.  The portal architecture is well maintained. There is no portal inflammation, vascular ectasia or intravascular fibrin deposit (thrombus). Focal portal fibrous expansion is noted but is judged to be within normal limit for subcapsular region.  Trichrom stain accentuates nodular pattern and reveals no significant fibrosis. These features are diagnostic of nodular regenerative hyperplasia (NRH). NRH is a morphologic pattern (“diagnosis”) that can result from a wide variety of causes. As in most cases, the underlying etiology is not histologically apparent.

The absence of significant fibrosis, portal vascular ectasia or intravascular thrombus essentially excludes hepatoportal sclerosis (idiopathic portal hypertension), cirrhosis and portal vein thrombosis, and makes focal nodular hyperplasia an unlikely diagnosis.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  57-year old man with HCC and h/o hep-C       

Native liver, liver transplantation (total hepatectomy):   

-- Hepatocellular carcinoma with extensive (>90%) coagulative necrosis consistent with thermotreatment effect (see Tumor Synopsis)

-- Micronodular cirrhosis with portal inflammation, lymphoid aggregate formation and rare patchy steatosis, consistente with clinical history of type-C viral hepatitis

-- Focal mild iron deposition in hepatocytes

-- No significant cholestasis or large bile duct injury identified

-- No significant histological abnormality in the gallbladder.

Editor's comment:

In addition to the tumor, presence and absence of common causes for liver cirrhosis (e.g., hep-C, hemochromatosis, alpha-1 anti-trypsin deficiency, PSC ect.) should also be reported.

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Clinical scenario:  5-year old boy, r/o Hirshprung's         

Liver, right lobe, core biopsy:   

-- Poorly differentiated carcinoma, present in four of eight biopsy cores, involving approximately 10% of the biopsy with maximal contiguous tumor line length of 4 mm, most likely of pancreatobiliary origin.

Note:  : Immunohistochemical stains, with adequate controls, show tha the tumor cells are positive for CK19, Ca19.9, Muc1 but are negative for CK20, CDX2, TTF1, Hepar1 and arginase.  The combined histologic and immunohistochemical findings support the above diagnosis.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  24-year old man.      

Liver, random needle core biopsy: 

-- Diffuse insoluable iron depositive in hepatocyte, pan-lobular pattern, grade 1 out of 3, highly indicative of hemochromatosis (see Note)

-- Minimal non-specific reactive changes (portal mononuclear inflammatory infiltrates and lobular disarray)

-- No significant portal or lobular inflammation, cholestasis, steatosis or fibrosis

-- Special stain for cytoplasmic hyaline globules is negative

Note:  Sections show three generous biopsy cores with an adequate number of portal tracts for evaluation. The changes in the liver biopsy borderline with mild abnormality and are non-specific. Special histochemical stain for iron show diffuse positive stain for cytoplasmic iron, grade 1 by Scheuer, indicative of heraditory hemochromatosis (in this age group). Of note, prior phlebotomy treatment can affect the histological grade of iron depositive. Quantitative iron analysis may be considered if the diagnosis can not be confirmed by genotypic study.

Reference:

Scheuer PJ, Williams R, Muir AR. Hepatic pathology in relatives of patients with hemochromatosis. J Pathol Bacteriol. 1962;84:53-64.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  47-year old woman       

Liver, random needle core biopsy: 

-- Moderate steatohepatitis, NAFLD score 6 (see NAFLD Score  and Note below)

-- No mallory hyalins, cholestasis, bile duct loss or granulomatous changes identified

-- Mild centrolobular fibrosis.

NAFLD Histologic and Fibrosis Score

Steatosis Grade: 2 (>33 - 66%)

Hepatocyte Ballooning Injury Grade: 2

Lobular Inflammation Score: 2 (2-4 foci per 200/field)

NAFLD Activity Score (NAS): >5 (Diagnostic of steatohepatitis)

NAFLD Fibrosis Stage: 3 (bridging fibrosis)

Note: The constellation of prominent macrovesicular steatosis, hepatocellular ballooning degeneration, lobular spotty necrosis and minimal portal inflammation is compatible with the diagnosis of steatohepatitis. The etiology underlying observed steatosis and inflammation is not histologically apparent.  Both alcoholic and nonalcoholic etiologies should be considered.

Reference:

Kleiner DE, Brunt EM, et al (for the Nonalcoholic Steatohepatitis Clinical Research Network).  Design and validation of a histological scoring system for nonalcoholic fatty liver disease.  Hepatology 2005; 41:1313-1321. . 

Editor's comment:

Although alcohol abuse and obesity as the underlying etiology can often be revealed by the histologic changes, a conservative reporting approach is to list likely etiologic differential diagnosis since biopsy is frequently performed to evaluate the severity of the disease or to confirm liver injury. For the working NFLD Score schema, please visit Grading Schema 

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Clinical scenario: 9-yo boy with BMI of 32 and family history of obesity        

Liver, needle core biopsy: 

-- Diffuse moderate microvesicular steatosis, etiology uncertain (see Note and NAFLD score below)

-- No lobular inflammation, Mallory hyalines, cholestasis, bile duct loss or granulomatous changes identified).

Note: The etiology underlying the observed steatosis is not histologically apparent. Although hyperlipidemia and obesity are common causes, lysosomal acidic lipase (LAL) deficiency should also be considered in this case. (need ref here). 

Editor's comment:

Prominent microvesicular steatosis in this age group with family Hx of obesity should be worked up to exclude LAL deficiency

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Clinical scenario:  58-year old woman with liver cirrhosis of unknown cause         

Native liver (1460 grams), explant (total hepatectomy):   

-- End stage liver disease with extensive micronodular cirrhosis (see microscopic description and comment).

-- Extensive fibrosis with bile ductular proliferation, mononuclear inflammatory infiltrate.

-- Patchy paracellular cholestasis, confirmed by bile stain.

-- No granuloma, periductal fibrosis or dysplasia or carcinoma identified.

-- PAS-D stain for intracytoplasmic hyaline globule and Perl's stain for iron are negative.

-- Trichrome stain confirms the cirrhosis.

Note: Although the micronodular cirrhosis, active fibrosis with bile ductular proliferation and mononuclear inflammatory infiltrate are compatible with the patient's clinical history of type-C viral hepatitis, these changes are not pathognomonic.  It is difficult to render a definitive etiological diagnosis. The micronodular cirrhosis pattern and absence of significant periductal fibrosis do not support PSC.  Relative preservation of centrilobular zone is not compatible with cirrhosis 2nd to steatohepatitis.  Negative stain for intracytoplasmic hyaline globule can exclude alpha-1 antitrypsin deficiency as the underlying etiology.  Iron deposition can be seen in both end-stage liver disease and hemochromatosis.

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  17-year old boy, r/o duodenitis       

Allograft liver, needle core biopsy (5 weeks post OLT):   

-- Moderate acute cellular rejection, RAI = 6 out of 9 (see Synopsis and Note).

-- No ischemic infarct, viral cytopathic change, cholestasis or steatosis.

Disease Feature Synopsis

Total number of portal tracts for evaluation: *

Number of portal tracts with inflammation: *

Portal inflammation: * (* out of 3)

Lymphocytic ductulitis: * (* out of 3)

Endotheliitis: * (* out of 3)

Rejection activity index: * out of 9

Bile duct loss: *

Foamy arteriopathy: *

Fibrinoid arteritis: *

Centrilobular congestion and hemorrhage: *

Geographic hepatocellular necrosis: *

Portal or central fibrosis: * (* out of 6)

Note: Dr. * is notified about the above diagnosis by phone on */*/2014. 

Editor's comment:

This section critics on the pro & con of the the wording. There will be 12-pt space after text paragraph.

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Clinical scenario:  16-month old boy with abdominal pain, weight loss and occasional diarrhea.      

Liver, wedge biopsy:      

-- Diffuse severe lobular cholestasis and hepatocellular degeneration associated with a decreased number of portal bile ducts, most compatible with paucity of bile ducts (intrahepatic biliary atresia).

-- No granuloma, ascending cholangitis or biliary cystic ectasia

-- Mild portal fibrosis

-- See microscopic description and Note

Microscopic Description and Note:  Sections reveal generous fragments of subcapsular region of the liver with an adequate numbers of portal tracts for evaluation.  There is an apparent decrease in the number of bile ducts in these portal tract (less than 0.5 bile ducts per portal tract) with (compensatory) small cholangiolar proliferation.  There is a significant mononuclear inflammatory infiltrate (predominantly lymphocytes) at the periphery of the portal tracts.  No portal granuloma or ductal bile stasis is identified.  Mild portal fibrosis is also noted.  The lobular architecture is relatively preserved.  The hepatic lobules are remarkable for diffuse severe hepatocellular degeneration associated with prominent lobular cholestasis (both cytoplasmic and canalicular type).  Rare extra-medullary hematopoiesis is noted in the sinusoids.  The paucity of the bile ducts in the portal tracts is confirmed by immunohistochemical stains for CK19.  PASD stain for cytoplasmic hyaline globules is negative.  Special stain reveals increase insoluble iron deposition predominantly in the interface (peripheral) zone of the lobule, graded 1-2 out of 4.  Rhodamine stain for copper binding protein is negative.

Given the patient's age and hepatic enzyme profile (predominantly as biliary obstructive pattern), the histologic findings are most compatible with the diagnosis of intrahepatic biliary atresia (paucity of ducts syndrome).  The differential diagnosis of alpha-1 antitrypsin deficiency, extra-hepatic biliary atresia, congenital hemochromatosis and Wilson's disease are also entertained but are essentially excluded by the combined histological, immunohistochemical and clinical findings.  Distinction of syndromic (Alagile's) from nonsyndromic intrahepatic biliary atresia cannot be made at this early stage histologically. Correlation with findings of physical exam and spine imaging would be more helpful. Genetic study of JAGGED-1 (JAG-1) may be considered if also clinically indicated.

Editor's comment:

Including such a long microscopic description and note may seem to contradict recommended report guidelines. However, for pathology diagnosis infrequently encountered (in your own practice), unfamiliar to your colleagues (or yourself), unexpected to the referring clinician, a well structure description with focus on diagnostic features, key ancillary studies and main DDx is very helpful.