| Abstract|| |
Liver resections are performed for acute and chronic end stage liver failure, primary and secondary liver malignancies as well as for several other neoplastic and non-neoplastic conditions. Hepatectomy specimens can be total, partial, or wedge resections. These specimens are relatively rare and complex. Meticulous handling, orientation, dissection, margin assessment, and reporting as per the latest guidelines, often require a multidisciplinary approach. This article discusses the approach to grossing of hepatectomy specimens, and the most important macroscopic considerations for specific conditions.
Keywords: Explants, hepatectomy, hepatocellular carcinoma, intrahepatic cholangiocarcinoma, liver transplantation, margins, partial resection, perihilar cholangiocarcinoma, transaction
|How to cite this article:|
Rastogi A. An approach to grossing of hepatectomy specimens. Indian J Pathol Microbiol 2021;64:121-6
| Introduction|| |
Liver resections are performed for malignant tumours such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PHC), carcinoma gallbladder (Ca GB), metastasis such as colorectal, several other benign and malignant conditions, and for liver failure in the centers performing liver transplantation. However, such surgical resection and liver transplantation are restricted to a very small proportion of early-stage malignancies, and these procedures are usually performed in dedicated liver surgical and transplant units. Owing to the relative rarity of such surgeries, pathologists are not well-versed with handling and grossing of these specimens. This article discusses various aspects of macroscopic evaluation and grossing approach according to current standard reporting guidelines and staging recommendations.
Multidisciplinary approach and understanding of liver segments
Liver surgical specimens handling demands a close coordination as well as information exchange, not just between a pathologist and surgeon, but oncologist, radiologist, and intervention radiologist also play a major role. Relevant clinical details including clinical differential diagnosis, pre-operative diagnosis, previous procedures/treatment, time of removal of specimen, segments resected, any frozen sections requirement, unfixed tissue allocation for research and bio-banking, suture labeling of the important margins, on-site evaluation of specimen by the surgeon –pathologist team for the orientation of these complex specimens and determination of critical foci of transection and other margins are a few aspects, where such multidisciplinary intervention is crucial.
The liver is divided into eight segments which form the basis of various surgical procedures of liver resection. These segments represent the watershed between the portions of liver perfused by main branches of hepatic artery and portal vein., Liver tumours are removed either by segmental resection or non-anatomical (wedge) resection. Total hepatectomy refers to resection of all the segments i.e., 1–8, right hepatectomy procedure removes segments 5–8, left hepatectomy is segments 2–4, right trisegmentectomy is segments 4–8, left lateral segmentectomy is segments 2–3, and left trisegmentectomy is segments 1–5 and 8. Pathologist records resections as wedge, partial (right or left lobe) resection or liver explants, as it is often not possible to assign segmental location, unless assisted by the surgeon [Figure 1].
|Figure 1: Gross specimens of total hepatectomy unfixed non-cirrhotic liver anterior view (a), posterior (b); fixed cirrhotic liver anterior view (c), posterior (d); liver segments in anterior (e) and posterior (f) diagram of liver|
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Types of surgical procedures (Specimens)
Total hepatectomy procedure is performed on the patients undergoing liver transplantation for acute liver failure, acute-on-chronic liver failure, and decompensated cirrhosis, attributable to a multitude of underlying etiologies as well as for malignancies such as HCC. Partial resections include lobectomy, trisegmentectomy, wedge resection of segments with/without- bile duct excision, gallbladder, lymph node dissection or major vein segment, which are performed for malignant such as HCC, ICC, PCC, Ca GB and colon-rectal metastasis, and a few benign and inflammatory-infective conditions.
Handling and orientation of resection specimens- general considerations
Meticulous handling and grossing forms the bedrock of a clinically relevant surgical pathology report. Liver resection specimens should be transferred immediately to the Pathology department, preferably in unfixed state. Allocation of tissue for future molecular studies (for e.g., Hepatoblastoma, hepatocellular carcinoma, paediatric conditions, and others) and for tissue biobank needs to be done in the Pathology department in the presence of a Pathologist. All the decisions in this respect, whether possible to provide tissue (i.e., without compromising diagnostic and staging criteria) and from which area and the amount, need to be decided and recorded by the Pathologist.
Liver explants as well as surgical specimens are weighed and the three dimensions recorded. Photographing the specimens before dissection is also a useful practice. Slicing for fixation is done, although thin slicing for macroscopic details is more accurate in the properly fixed hardened tissue. Identification of liver transection margin, porta hepatis structures, as well as painting/inking them before further slicing, is very important. The specimen is then transferred to neutral buffered formalin for fixation, which is required for 12-24 hours. All the separately sent tissue specimens and those identified in the same container should be described.
Details of slicing and margins differ according to the specimen types and are thus discussed separately with individual malignancies.
Grossing approach for total hepatectomy specimen
Total hepatectomy specimen (liver explants) received for the non-neoplastic conditions (mostly, acute or chronic decompensated liver failure) are oriented by identifying the four lobes- right, left, caudate, and quadrate. The latter two are best appreciated on examination of the under-surface of the liver. The caudate lobe lies between the portal vein and the inferior vena cava. The quadrate lobe is between the gallbladder fossa and the ligamentum teres, and is separated from the caudate lobe by the portal vein.
First dissect the gallbladder from its bed, open, rinse out the bile, and weigh the specimen. Representative sections of the neck, body, and fundus of the gallbladder are taken. Examine the peritoneal lined capsular surface of the liver. This should be smooth, glistening, and unremarkable. Examine and record dimensions of any disruption, plaque, hemorrhage, or hematoma, on the capsular surface.
Begin the dissection at the liver hilum. The major structures forming the porta hepatis are the bile duct, hepatic artery, and portal vein. These are frequently transected very close to the liver however still identifiable as are often sutured or clipped by the surgeon. The duct is most anterior and to the right, the artery is to the left, and the vein is most posterior. Submit shave margin sections from the bile duct, hepatic artery, and portal vein. Identify, probe, and take sections en face from left, right, and middle hepatic veins.
Serial sections (thin slicing at 5 mm in case of a decompensated cirrhosis and acute-on-chronic liver failure) of liver perpendicular to the long axis of explants are cut. Three sections each from the right and left lobes, and one section each from the caudate and quadrate lobes, is adequate representation for a non-neoplastic etiology. Any pathology such as cyst, incidental adenoma, hematoma, and thrombi are described and archetypal sections are taken.
Cirrhotic explants might contain a metallic intravascular stent due to a prior transjugular intrahepatic portosystemic shunt (TIPS) procedure; this is removed by cutting tissue circumferentially around it. Liver cirrhosis is often due to infective etiologies, therefore careful handling and universal precautions are necessary. In liver explants for biliary atresia with prior Kasai's portoenterostomy, and for primary sclerosing cholangitis, slicing parallel to the porta is often helpful. The appearance of the extrahepatic biliary anatomy should be recorded.
Handling and orientation of liver explants, which harbor HCC, are nearly the same. Careful examination of the surface of liver to identify any bulge due to the intraparenchymal mass or any fragmentation of capsule over the mass should be reported. Slicing (ideally at 5 mm, and no more than 10 mm thick) perpendicular to the long axis of specimen in case of a single large mass, and along the long axis in case of multicentric HCC, provide the best assessment. Photography of heterogeneous areas is quite helpful during macroscopic-microscopic correlation [Figure 2].
|Figure 2: Gross specimens of hepatectomy specimens showing perpendicular (a) and parallel (b) slicing; incidental HCC on thin slicing (c); tumour bulge on capsular surface (d); Transection margin (e) and hilar structures (f) of partial hepatectomy specimen|
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Essential elements of the gross examination of mass are size, number, location, colour, consistency, vessel invasion and relationship to adjacent cirrhotic/non-cirrhotic liver. This encompasses all the pathologic datasets for pT staging as recommended in the 8th edition of AJCC. Additionally, presence or absence of necrosis, hemorrhage, and scarring, along with the gross types of nodule- circumscribed, vaguely nodular, confluent, diffuse, or massive should ideally be recorded.,, Lymph nodes, if identified in the soft tissue of liver hilum, should also be sampled. Gall bladder bed tissue is sampled in case of tumour lying adjacent to this area. Macroscopic involvement (or <5 mm distance between tumour and margin) of the main left or right branch of the portal vein or any of the three main hepatic veins should be specifically recorded. This information is important for accurate pathological staging.,,,
In case of a single large tumour, usually 3-4 blocks, as well as sections from the tumour/adjacent liver interface, is essential. All the heterogeneous areas should be represented. For multiple tumours, recording of size and complete gross details as well as at least one section from each major tumour nodule, and adequate sampling with recording of size range and location of the smaller tumours, is ideal. Satellite nodules, multifocal HCC, and intrahepatic metastases, all are considered multiple tumors for pT staging.,
Representative tissue block from the background liver should be prepared, irrespective of whether or not it is macroscopically abnormal. The presence of fibrosis or cirrhosis should be recorded., Non-cirrhotic liver demands a cautious consideration of specific tumours such as fibrolamellar HCC, hepatic adenoma, focal nodular hyperplasia, and metastasis.,
Grossing approach for partial hepatectomy specimen
Partial resection specimens received in Pathology range from small wedges to an entire lobe. Approach follows the same rules as for complete resections, except certain peculiarities. Proper orientation of these specimens is difficult but crucial. Partial hepatectomy specimens have at least one surface that shows exposed hepatic parenchyma i.e., absence of smooth capsule. This transection margin is rough, fragmented, bloody, with cautery effect, making it easy for identification. This, along with extrahepatic biliary duct margins and any tissue adherent to the liver capsule should be painted/inked.
The specimen is oriented and the three dimensions are measured. Other structures such as extrahepatic bile duct, gallbladder, and lymph nodes, if included, should be measured. Specimen slicing is performed at right angles to the cauterized edge. However, when the tumor tissue is far away from the surgical margin, slicing parallel to the surgical margin, is preferable.
Initial sections through the center of nodule, best demonstrates its closeness to the transection margin. Sections from the periphery of HCC are less likely to be necrotic and are more informative, especially tumour near liver capsule, tumour- parenchyma interface, and inked margin closest to the nodule. If the margin is grossly free and more than 2 cm away from the nodule, a random section of margin is sufficient. Distance from the closest nodule should be measured. Shaved bile duct and vascular margins are cut; however, few of these margins are often either received separately for intra-operative frozen section examination or tagged with suture by the surgeon for easy identification.
Cholangiocarcinoma is classified into intrahepatic, perihilar, and distal types. ICC arises from intrahepatic bile ducts that extend from the periphery of the liver to the second-order bile ducts. ICC has characteristic growth patterns. Most common is the mass-forming type; however periductal infiltrating, intraductal growth, or their combinations are also often seen. Surgical procedures include partial hepatectomy, wedge resection, or even total hepatectomy. Specimen slicing, sectioning, and margin assessment for the mass forming type follow the same principles as HCC. Longitudinal sectioning of bile ducts and examination of bile duct margins become essential elements if the mass is located close to liver hilum or display a mixed mass forming-periductal growth. Macroscopic involvement of vessels should be recorded. Bile ducts margins are received intra-operatively, else examined in the main surgical specimen. Regional lymph nodes (usually ≥6) are dissected.
Perihilar or hilar cholangiocarcinoma arises from the biliary tract epithelium in the hilum of liver i.e., bile duct above the junction of the common hepatic duct and the cystic duct, and up to the second-order divisions of the left and right hepatic duct., The site of tumour is described according to the ducts involved macroscopically. The common surgical specimen is partial hepatectomy with resection of the extrahepatic biliary tract in combination with complete lymphadenectomy of the hepatoduodenal ligament. This specimen is particularly complex. Proper assessment of resection planes, margins, and careful dissection is of utmost importance. Therefore, most of the time surgeon identifies or marks these structures with sutures/ties or aids in identification.
Resection planes and margins include: Common bile duct, proximal/segmental bile ducts, hepatic artery, portal vein, liver parenchyma transection margin, and the circumferential periductal dissection plane., Tubular segment of proximal and distal duct margins are assessed intra-operatively by frozen section examination. Once margins are identified and the specimen is oriented, careful dissection of hilar bile ducts is done to assess the extent and depth of invasion. Periductal infiltrating growth pattern is the characteristic gross appearance, with/without an associated mass lesion. Involved bile ducts are opened longitudinally or multiple transverse sections are cut, with the advantages of accurate assessment of the mucosal extent of involvement and extensive examination of circumferential surfaces, respectively., The length of extrahepatic bile duct should also be recorded.,
Post-treatment liver resections
Patients with HCC waiting for transplantation or planned for surgical resections, often undergo various loco-regional therapies such as radiofrequency ablation and transarterial chemoembolization., Grossing and sectioning recommendations require sampling of entire cross-section if the tumour is <2 cm, with additional sections for each 1 cm for larger tumours, and reporting the extent of necrosis and size of viable tumour in the largest five nodules [Figure 3].,, Further sections from the tumour periphery and capsule should be taken, in case no viable tumour is found in the initial sections.
|Figure 3: Gross appearance of multifocal HCC (a); HCC in non-cirrhotic background (b); Necrotic HCC post-TACE (c); Intrahepatic cholangiocarcinoma (d) and Mixed hepato-cholangiocarcinoma in non-cirrhotic background (e); periductal type (f) and periductal with mass forming type (g) of perihilar cholangiocarcinoma; Liver wedge resection for metastasis of colonic adenocarcinoma (h)|
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| Carcinoma Gallbladder|| |
The venous drainage of gallbladder is through cholecystic veins that enter the liver through the gallbladder fossa (segment IVb and V). Extended radical cholecystectomy specimens can include: Non-anatomical wedge resection of the gallbladder fossa with a ≥2 cm rim of non-neoplastic liver tissue, or a more extensive anatomical surgical resection of liver segments 4b and 5, with resection of the biliary tree and regional lymph node dissection., Gall bladders should be opened longitudinally from the serosal surface to avoid disruption of the GB bed margin. When liver resection is performed in cases with incidental Ca GB, the site of gallbladder bed is inked and the entire GB bed is embedded in serial blocks. Liver transection margin and bile duct margins, according to the extent of resection, are examined as described in the earlier sections.
Liver resection specimens for metastasis
Colorectal liver metastasis (CRLM) specimen is a prototype. The grossing approach is fundamentally the same. The report should document the site, size and appearance of each lesion. Two-three sections from single viable tumour are sufficient. However in case of multiple nodules, histological sampling of each of them is recommended. Section from the periphery of the tumour, and of the nodule closest to transection margin should be taken. Hilar lymph node should be examined for tumour.
Hepatectomy specimens with paediatric tumours such as hepatoblastoma, mesenchymal hamartoma, embryonal sarcoma, etc., are handled in the similar manner. However, sampling of all heterogeneous areas and submission of sections from both central and peripheral parts of lesion is required. Excised cystic lesions should be carefully dissected to look for the communication of cyst to the biliary system, loculation, quantity and quality of fluid, presence of any papillary projections or nodules. Liver specimen grossing guidelines for other neoplastic and non-neoplastic lesions in children and adults in principle remains the same.
Other essential elements are the margin status and assessment of response to therapy.
[Table 1] and [Figure 4] summarize the stepwise approach to grossing of hepatectomy resection specimens
|Figure 4: Grossing steps of liver explant (decompensated cirrhosis) a-e: Fresh specimen orientation with probes in the hepatic veins (a), gallbladder removal (b), identification of suture marked porta hepatis structures (c), thin slicing of formalin fixed specimen (d), and sampling and section taken from cut surface (e); Liver explant with HCC in cirrhotic background (f-j): Unfixed specimen with outer surface showing tumour bulge (f), cut surface with single greenish well-circumscribed HCC in left lobe (g), fixed specimen with serial slicing perpendicular to the long axis of explants shows mixed nodularity of outer surface and HCC (h), cut surface showing relation of HCC to the left hepatic vein (i) and to the inked porta (j)|
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|Table 1: Stepwise approach to grossing of hepatectomy resection specimen|
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| Conclusion|| |
Hepatectomy specimens are rare and complex, but a very important source of understanding liver anatomy, tumour stage, and macroscopic heterogeneity. Proper handling, grossing approach and margin assessment are the basis of a clinically useful hepato-biliary surgical pathology report, which is highly dependent on multidisciplinary collaboration.
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Conflicts of interest
There are no conflicts of interest.
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Department of Pathology, Institute of Liver and Biliary Sciences (ILBS), Delhi
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]