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When a potential cause is identified, more definite confirmation of the cause is often difficult because patients tend to have debilitating illnesses and are on numerous medications, making it almost impossible to isolate a specific etiology. Nonetheless, associations have been made with total parenteral nutrition therapy, congestive heart failure, and alcoholic hepatitis. In the setting of severe alcoholic hepatitis, a bile ductular pattern of cholestasis is associated with an increased risk of subsequently developing clinical sepsis, 12 though the reason s are unclear.

Synonym: Cholangiolar cholestasis, cholangitis lenta Bile ductular metaplasia Experimental evidence suggests that liver injury can cause a reparative response where mature hepatocytes transform into bile ductules, a process called bile ductular metaplasia. The proliferating bile ductules are dilated by bile plugs. The patient was not septic. Bile ductular reaction A bile ductular reaction is defined as increased numbers of ductules at the periphery of the portal tract Fig.

In the normal liver, the portal tracts have few or no visible bile ductules. However, in response to liver injury, there can be a ductular proliferation, as the bile ductules are a source of liver progenitor cells and proliferate in response to injury. In other cases, the ductular reaction is the major pattern of injury and there is little or no lobular injury. This latter pattern can be accompanied by neutrophils and sometimes by portal tract edema and suggests biliary obstruction.

Many times a bile ductular reaction shows admixed neutrophils Fig. The admixed neutrophils should be in the stroma associated with the proliferating ductules and not in the lumen of the bile duct proper. Neutrophils in the main duct of the portal tract suggest ascending cholangitis, especially if the bile duct is dilated and the lining epithelium is attenuated Fig. The ductular reaction is one of the key injury patterns in the liver. Historically, Popper and colleagues 13 were one of the first users of the term ductular reaction. They further subdivided ductular reactions into three types 14 : type I, associated with biliary obstruction; type II, associated with significantly active hepatitis; type III, associated with massive liver necrosis.

This terminology of types I, II, and III is no longer used, but serves as a useful reminder of the major types of injury that can lead to a ductular reaction. Synonym: Bile ductular proliferation, pericholangitis obsolete Figure 3. The portal tract shows marked ductular proliferation in this liver biopsy from a case with biliary obstruction. These proliferating bile ductules are associated with mild neutrophilic and lymphocytic inflammation.

Bridging fibrosis The term bridging fibrosis is used when fibrous bands extend from either one portal tract to another portal tract Fig.

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Synonyms are septal fibrosis and fibrous septa. Of note, however, there is nonuniform usage of these latter terms, especially the term fibrous septa. Although most authors use fibrous septa as a synonym for bridging fibrosis, occasional authors use the term fibrous septa to describe short fibrous extensions from the portal tracts that do not actually connect two portal tracts, and thus would not be the same as bridging fibrosis.

Synonym: Septal fibrosis, fibrous septa inconsistently used Figure 3.

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Bridging fibrosis in a case of steatohepatitis. Bridging necrosis With bridging necrosis, the lobules show an irregular band of dead hepatocytes that extends from central vein to central vein, central vein to portal tract, or less commonly from portal tract to portal tract. In the band of necrosis, the tissue often shows collapse and variable inflammation. This pattern is not specific for an etiology, but does indicate a severe liver injury. This pattern is most commonly seen in the setting of markedly active hepatitis or toxin exposure.

Canal of hering The canal of Hering connects the lobules to the biliary tree. Canals of Hering are formed partly by cholangiocytes and partly by hepatocytes. The canals of Hering often go in and out of the plane of section, so they may appear discontinuous on a single slide, but serial sections show a continuous line of cells extending from lobules into the portal tracts. Cholangiocyte Cholangiocytes are the epithelial cells that line the bile ducts and bile ductules. The canals of Hering are lined partly by hepatocytes and partly by cholangiocytes.

Synonym: Biliary epithelial cell Cholate stasis Cholate stasis is defined as swollen, pale hepatocytes located in zone 1 periportal , resulting from injury because of chronic exposure to bile acids Fig. Cholate stasis results from chronic cholestasis. The hepatocytes in cholate stasis are sometimes confused for ballooned hepatocytes. Although there are some general similarities resulting from cell swelling, they are quite different.

In cholate stasis, larger groups of often contiguous periportal hepatocytes are pale and swollen, whereas ballooned hepatocytes tend to be found as single, enlarged cells. As noted previously, cholate stasis affects the zone 1 hepatocytes, in contrast to the balloon cells in steatohepatitis, which are found mostly as scattered single cells, often in zone 3.

The background changes are also distinct, as cholate stasis is seen in the setting of chronic cholestasis, whereas ballooned hepatocytes primarily occur in the setting of steatohepatitis. Mallory hyaline can be found in both cholate stasis and ballooned hepatocytes. Copper stains typically show scattered, though often sparse, granules of copper in cholate stasis.

A CK7 is also positive for intermediate hepatocytes in cholate stasis, but does not stain balloon cells in fatty liver disease. Synonym: Feathery degeneration, psueodoxanthomatous changes obsolete Figure 3. In this case of biliary cirrhosis, the hepatocytes at the edges of the cirrhotic nodules show swelling and Mallory bodies.


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The location of the bile varies in different cases and in most cases can be seen in multiple different compartments, with hepatocellular cholestasis the most common, followed in descending order of frequency by cholestasis involving the bile canaliculi, the proliferating ductules, and the bile duct proper. In general, the nonhepatocellular forms of cholestasis take longer to develop and are associated with more severe cholestasis.

Outside of this general correlation with the severity and length of cholestasis, there is little or no additional diagnostic information contained in identifying bile in the hepatocytes versus nonhepatocyte location.

The ductular cholestasis pattern has been linked to sepsis, 15 , 16 but is actually seen in many other severely cholestatic conditions and has little or no diagnostic specificity for sepsis. Furthermore, the major pattern of injury in sepsis is actually a nonspecific hepatitis and fatty change. The best histological finding that can support a diagnosis of chronic hepatitis is convincing fibrosis, though the opposite is not true, as many cases of chronic hepatitis can take years to decades to start fibrosing.

Chronic active hepatitis This term is no longer used, but is of interest for historical reasons. One of the earliest attempts to better understand this question focused on histology, dividing cases into chronic active hepatitis versus chronic persistent hepatitis. Chronic active hepatitis was thought to have the greatest risk for fibrosis progression and was defined by the presence of piecemeal necrosis now called interface activity and either periportal or septal fibrosis.

In contrast, chronic persistent hepatitis also see entry below had a good prognosis and was defined by having absent or slight piecemeal necrosis and either no fibrosis or portal fibrosis. This approach deeply influenced the thinking of the pathology community but eventually had to be abandoned when data showed it did not predict disease progression.

However, the notion of piecemeal necrosis interface activity still has clinical relevance and is part of essentially all modern grading systems for chronic hepatitis. The duality of portal fibrosis versus periportal fibrosis has also persisted in some staging systems, but perhaps more because of inertia than biological relevance, as mostly they are about the same thing.

Synonym: Chronic aggressive hepatitis also obsolete Chronic persistent hepatitis This term is obsolete but of historical interest. Early efforts to understand risk factors for fibrosis progression divided cases of chronic into one of two broad histological patterns: chronic active hepatitis versus chronic persistent hepatitis. Nonetheless, Sir William Osler to , a prominent and dominant North American physician, one of the four founders of Johns Hopkins Hospital, gave Laennec the credit for describing cirrhosis in his very influential English language medical text books, and this seems to have stuck.

Confluent necrosis indicates a more severe pattern of hepatic injury. Confluent necrosis most commonly affects zone 3 hepatocytes, but with severe necrosis can extend to other zones of hepatocytes. The distinction between single cell necrosis and confluent necrosis in clinical practice should be made using common sense and with the goal in mind of conveying the overall findings in the biopsy. For example, if a biopsy specimen shows predominately spotty necrosis, but by carefully searching you also find a single area with 3 adjacent dead hepatocytes, the best descriptor for the overall pattern of injury is still spotty necrosis.

In cases with severe confluent necrosis, bridging necrosis is also commonly found. Councilman body Councilman body is no longer a commonly used term, being replaced in the current literature by the terms apoptotic body or acidophil body. However, the term is of historic interest and is occasionally encountered in modern literature.

Councilman bodies are named after the American pathologist William Councilman to , who described apoptotic hepatocytes as a dominant finding in the pathology of yellow fever. Synonym: Councilman hyaline body, acidophil body, apoptotic body, spotty necrosis Ductal plate malformation Ductal plate malformations can be diffuse in the setting of inherited polycystic liver and kidney disease or in the setting of congenital hepatic fibrosis, being found in most of the portal tracts.

However, similar lesions can also be acquired, being found as single or small numbers of lesions, seen more commonly in cirrhotic than in noncirrhotic livers. Ductal plate malformations are composed of elongated, interanastomosing bile ducts. They can encircle the portal tract in syndromic settings such as congenital hepatic fibrosis Fig. In other cases, particularly the sporadic lesions, they can form small nodules at the edges of portal tracts.

Larger lesions can be grossly visible. The ducts typically have open lumens and bile plugs and are growing in a dense fibrotic background. Sporadic lesions are also commonly called von Meyenburg complexes. Synonym: von Meyenburg complex used mostly in nonsyndromic cases , bile duct hamartoma used mostly in nonsyndromic cases Ductopenia Ductopenia is defined as a reduction in the number of bile ducts. However, early ductopenia can be very challenging to diagnose because in normal liver tissue some of the smaller portal tracts will not have bile ducts, potentially leaving you to wonder if your case is within normal limits or shows very early duct loss.

Chronic inflammation in the portal tracts can obscure bile ducts and an immunostain should be used to confirm bile duct loss. Also of note, ductopenia can be accompanied by patchy bile ductular proliferation, so make sure you assess the bile ducts proper and not the bile ductules. This biopsy is from a person with congenital hepatic fibrosis. Like all medical disciplines, liver pathology has its own vocabulary used to describe histological findings.

Technically, this term could refer to any nonnormal artery, but in common usage this term refers to an artery located in the hepatic lobule, instead of their normal location in the portal tract Fig. A single dead cell is referred to as an acidophil body Fig. Synonym: Apoptotic body, spotty necrosis, Councilman body. The hepatic acinus is the functional unit of the liver and is usually illustrated as an elliptical or diamond shaped structure with ends in the portal tract and a bulging middle extending from central vein to central vein.

This term is commonly used to refer to any abrupt presentation of liver disease. This term is used in gross pathology. As formally defined, an apoptotic body results when a cell undergoes programmed cell death. Ballooned hepatocytes are enlarged, have rarified cytoplasm, and may contain Mallory bodies. Hepatocytes with ballooning degeneration are enlarged, rounded, and have rarified cytoplasm. The bile duct is a tubular structure located in the portal tract that is lined by a simple cuboidal to low-columnar epithelium, which is composed of cholangiocytes.

Bile duct duplication is associated with chronic obstructive biliary tract disease, such as primary sclerosing cholangitis or other stricturing processes. Bile ducts can undergo metaplasia, usually in the setting of chronic biliary tract disease. Bile duct hamartomas are composed of benign duct-like structures, usually with open lumens and bile deposits Fig.

Synonym: Ductal plate malformation, von Meyenburg complex. This descriptive term is used to report lymphocytes within the bile duct epithelium, a finding that is often associated with bile duct injury Fig. A bile infarct can be seen with high grade, often acute, obstruction of the biliary tree or with long standing cholestasis. Bile ductules are different than the centrally located bile duct.

Bile ductules will occasionally be distended by bile plugs Fig. Experimental evidence suggests that liver injury can cause a reparative response where mature hepatocytes transform into bile ductules, a process called bile ductular metaplasia. A bile ductular reaction is defined as increased numbers of ductules at the periphery of the portal tract Fig.

Synonym: Bile ductular proliferation, pericholangitis obsolete.

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The term bridging fibrosis is used when fibrous bands extend from either one portal tract to another portal tract Fig. Synonym: Septal fibrosis, fibrous septa inconsistently used. With bridging necrosis, the lobules show an irregular band of dead hepatocytes that extends from central vein to central vein, central vein to portal tract, or less commonly from portal tract to portal tract. The canal of Hering connects the lobules to the biliary tree. Cholangiocytes are the epithelial cells that line the bile ducts and bile ductules.

Cholate stasis is defined as swollen, pale hepatocytes located in zone 1 periportal , resulting from injury because of chronic exposure to bile acids Fig. Synonym: Feathery degeneration, psueodoxanthomatous changes obsolete. Chronic hepatitis is often used somewhat informally by pathologists to describe any lymphocytic inflammation in the liver, but such usage should be discouraged, as the term chronic hepatitis does have a distinct clinical implication, where it is commonly defined as elevated serum enzyme levels for greater than 6 months.

This term is no longer used, but is of interest for historical reasons. This term is obsolete but of historical interest.

Cirrhosis is a diffuse fibrosis of the liver leading to parenchymal nodularity. Councilman body is no longer a commonly used term, being replaced in the current literature by the terms apoptotic body or acidophil body. Synonym: Councilman hyaline body, acidophil body, apoptotic body, spotty necrosis. Ductal plate malformations can be diffuse in the setting of inherited polycystic liver and kidney disease or in the setting of congenital hepatic fibrosis, being found in most of the portal tracts.

Synonym: von Meyenburg complex used mostly in nonsyndromic cases , bile duct hamartoma used mostly in nonsyndromic cases. Ductopenia is defined as a reduction in the number of bile ducts. Only gold members can continue reading. Log In or Register to continue. Like this: Like Loading Tags: Surgical Pathology of the Liver. Finally, the results of this study should be interpreted and discussed within the context of a clinical culture of respect and humility.

Consensus often only approximates truth even in ideal clinical settings. Curiosity, ambivalence, and skepticism each may influence ambiguity in its own particular way. Nevertheless, the wise clinical management of uncertainty is achievable and, fortunately, is apparent in high-quality medical practices even today. National Center for Biotechnology Information , U. Journal List Acad Pathol v. Acad Pathol. Published online Jul Blake A. Elizabeth A.

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Ronald S. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Email: ude. This article has been cited by other articles in PMC. Abstract In order to document perceptions of text comments appearing in surgical pathology reports, questionnaires were distributed to 4 groups of caregivers: university staff pathologists, resident pathologists, faculty clinicians other than pathologists , and resident clinicians at a teaching hospital. Keywords: diagnostic accuracy, free-text comments, human performance studies, interobserver variability, medical errors, quality measures, surgical pathology reports.

Introduction A surgical pathologist renders both qualified and unqualified diagnoses. Methods This study received a waiver from the institutional review board. Phase 1 In the first phase of this study, an anonymous question survey was handed out to staff surgical pathologists and pathology residents during departmental meetings.

Table 1. Common Surgical Pathology Phrases. Open in a separate window. Phase 2 In phase 2 of the study, an anonymous questionnaire was given to clinician staff physicians ie, attending physicians and clinical residents at interdisciplinary tumor boards or conferences. Figure 1. Figure 2. Figure 3. Figure 4. Table 2. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Figure Discussion A previous British study showed that there was variability in the intended level of certainty communicated using a 1 to 5 scale for the 13 most common diagnostic phrases used at a British hospital.

References 1. Communicating diagnostic uncertainty in surgical pathology reports: disparities between sender and receiver. Pathol Res Pract. Is terminology used effectively to convey diagnostic certainty in radiology reports? Acad Radiol. Radiology reporting: attitudes of referring clinicians. Pulmonary embolism: lung scanning interpretation—about words. Kenney RM. Between never and always. N Engl J Med. Toogood JH. Antil JH. Uses of response certainly in attitude measurement. Adv Consumer Res. Attitude certainty: a review of past findings and emerging perspectives.

Soc Personality Psych Compass. Phraseology in pathology reports. A comparative study of interpretation among pathologists and surgeons. J Clin Pathol. Galloway M, Taiyeb T. The interpretation of phrases used to describe uncertainty in pathology reports. Pathol Res Int. Cytologic diagnosis: expression of probability by clinical pathologists. Vet Clin Pathol. Clinicians are from Mars and pathologists are from Venus: clinician interpretation of pathology reports. Arch Pathol Lab Med. Eye-movement study and human performance using telepathlogy virtual slides.

Implications for medical education and differences with experience. Hum Pathol. Characterizing the development of visual search expertise in pathology residents viewing whole slide images. Domen RE. The ethics of ambiguity: rethinking the role and importance of uncertainty in medical education and practice.

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