—  SHORT COURSE #22  —


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Introduction.
Primary tumors of the liver are divided into benign and malignant epithelial and non-epithelial neoplasms. The epithelial neoplasms are the most common, and fall predominantly into the hepatocellular and bile-ductular types. However, in addition, other nonneoplastic, tumor-like lesions of various types can be of significance as well. The World Health Organization's classification scheme which includes both neoplasms and tumor-like lesions is listed in Table 1.

Reporting of tumor resection specimens.
The verification of tumor type and status as a primary or metastatic neoplasm versus a nonneoplastic tumor are the most important considerations in the diagnosis. The descriptive comments should focus on information important for tumor staging such as tumor size (smaller or larger than 2 cm), number of lesions (single or multiple), which lobes (or segments) are involved, local extension of the lesion outside of the liver, and the presence or absence of gross vascular invasion, especially noting which of the major vessels (portal or hepatic vein) are involved. Microscopic evaluation of a mass should have adequate numbers of sections relative to tumor size in order to evaluate for vascular invasion or extension outside of Glisson's capsule, since these factors which are associated with decreased survival. Sections near the edge of the tumor are generally recommended to identify vascular invasion if gross invasion is not noted. Any gross observation of possible large vessel invasion should be documented microscopically. A section of nonneoplastic liver should also be included in order to identify any significant pathology.

Generally, it is recommended that the surgical margins of the resection should be inked prior to sectioning the tumor in order to more definitively evaluate the distance from the margin to the tumor, and the status of the resection margins should be included in the report. Some studies have suggested that a tumor-free margin of at least 1cm may be directly related to a better prognosis for some malignant tumor types. Other studies have shown that more extensive resections of hepatocellular carcinomas are preferable to limited excisions when the lesion is small. Thus, the distance from tumor to the closest margin of resection should be documented.

Biopsy samples- special considerations
Both small core and fine needle aspiration biopsy (FNAB) are often utilized successfully for the diagnosis of specific tumor types. However, it is important to remember that the accuracy of the FNAB can be enhanced by utilizing extra tissue preprations such as cell buttons in order to evaluate the microhistology of paraffin embedded sections of the sample collected from the FNAB material. Utilization of such methodology is especially helpful in the evaluation of well-differentiatied lesions of hepatocellular type, in which subtle cytologic features such as the cell size, crowding of nuclei, and increased nuclear:cytoplasmic ratio or architectural features such as the formation of trabeculae or the width of the cell plates may be difficult to assess on smears alone. In these instances, the use of histologic sections in combination with well-prepared smears are highly successful in differentiating the well-differentiated hepatocellular carcinoma from other lesions such as adenoma, focal nodular hyperplasia, large regenerative nodules, or dysplastic nodules. In addition, preparation of the cell button in cases of poorly differentiated neoplasms or in tumors with unusual morphology can result in more accurate diagnoses by the application of immunoperoxidase techniques to these samples.

Since the biopsy material is often quite limited in amount, it is recommended that slides of unstained material also be cut when the block is initially sectioned in order to insure that sufficient material will be available if it becomes necessary to evaluate additional level sections or other stains. It is also advised that the usual panel of stains (which often include trichrome, reticulin, PASD, and iron stains) should not be ordered automatically at the time of gross examination as this excess sectioning (before examination of the H&E morphology) often depletes the block of the diagnostic material so that sufficient tissue may not be available for other more diagnostic stains.

Case #1 - Focal Nodular Hyperplasia (FNH)

Clinical Summary
41 year old man who was undergoing a total proctocolectomy for rectal cancer was found at surgery to have a liver mass. The mass measured 6 cm and was nodular. The surrounding liver was unremarkable.



Case 1 - Figure 1 - Nodular liver parenchyma with central scar (arrow), low power

Case 1 - Figure 2 - Large irregular vessel in an area of fibrosis, medium power

Case 1 - Figure 3 - Bands of fibrosis with chronic inflammation and proliferationg bile ductules (arrows), medium power




Case #2 - Hepatocellular Adenoma (HA)

Clinical Summary
30 year old woman with chest pain and RUQ pain for 6-9 months. Abdominal U/S demonstrated a liver mass that was confirmed with abdominal CT and MRI. The tumor was 8 cm and hemorrhagic while the adjacent liver appeared normal.



Case 2 - Figure 1 - Hepatocellular proliferation with areas containing fibrin and hemorrhage, low power

Case 2 - Figure 2 - Bland hepatocytes and vessels with no bile ducts, medium power

Case 2 - Figure 3 - Bland hepatocytes and thin walled vessel with no bile ducts, high power

Case 2 - Figure 4 - Hepatocytes arranged in two-cell-think liver plates with intact reticulin Framework, H&E and reticulin stains, medium power




Case #3 - Small Hepatocellular Carcinoma

Clinical Summary
45 year old man with cirrhosis who underwent a liver transplant. In his explant, a 1.5 cm nodule was found in the background of a cirrhotic liver.



Case 3 - Figure 1 - Cirrhotic liver with a dominant nodule (arrow), low power

Case 3 - Figure 2 - Atypical hepatocytes with thickened cell plates, medium power

Case 3 - Figure 3 - Atypical hepatocytes with thickened cell plates, hight power

Case 3 - Figure 4 - Cell plates greater than 2-3 cells thick, H&E and reticulin stains, medium power




Case #4 - Hepatocellular Carcinoma, Pseuglandular and Clear Cell Pattern

Clinical Summary
62 year old man with history of colon cancer, presented with 2 month history of shoulder and epigastric pain. Abdominal MRI showed a 5 cm tumor in the lateral segment of the left hepatic lobe.

Case 4 - Figure 1 - Hepatocellular carcinoma, pseudoglandular pattern, medium power

Case 4 - Figure 2 - Hepatocellular carcinoma, clear cell variant, medium power

Case 4 - Figure 3 - Hepatocyte immunostain with granular cytoplasmic positivity, medium power



Case 4 - Figure 4 - pCEA immunostain with luminal and canalicular positivity, medium power

Case 4 - Figure 5 - Negative MOC31 immunostain, medium power




Case #5 - Metastatic Renal Cell Carcinoma

Clinical Summary
53 year old man who was found to have a 3 cm mass in his liver on an abdominal CT scan.



Case 5 - Figure 1 - Clear cell carcinoma (arrow) metastatic to the liver, low power

Case 5 - Figure 2 - Clear cell carcinoma, high power

Case 5 - Figure 3 - EMA positivity, hight power




Case #6 - Bile Duct Adenoma

Clinical Summary
40 year old man with cirrhosis who underwent a liver transplantation. The explant liver contained a 1 cm tan firm nodule in that appeared different from the surrounding nodules.



Case 6 - Figure 1 - Cirrhotic liver with a nodular proliferation of ducts in a fibrotic area, low power

Case 6 - Figure 2 - Ductular structures with a tubular appearance in a fibrotic stroma with some lymphocytes, medium power

Case 6 - Figure 3 - Ducts with no cytologic atypia, high power




Case 7 - Biliary Cystadenoma

Clinical Summary
32 year old asymptomatic woman with a large palpable non-tender mass in her RUQ found on physical exam. CT scan showed a mass in the liver. The mass was cystic and measured 8 cm



Case 7 - Figure 1 - Multilocular cyst partially denuded with an epithelial lining, low power

Case 7 - Figure 2 - Mucinous epithelium with basally oriented nuclei and an underlying "ovarian type" stroma, medium power




Case 8 - Intraductal Cholangiocarcinoma (Biliary Papillomatosis)

Clinical Summary
54 year old woman with cirrhosis and a history of ulcerative colitis. She presented for pre-liver transplant evaluation and abdominal CT demonstrated marked hepatomegaly and severe dilation of biliary tree, suggestive of obstruction of the common hepatic duct. At gross examination, multiple ducts were found to contain papillary excrescences.



Case 8 - Figure 1 - Intraductal paillary proliferation of columnar epithelium and adjacent fibrotic liver, low power

Case 8 - Figure 2 - Intraductal papillary proliferation (arrow), medium power

Case 8 - Figure 3 - Severely dysplastic columnar epithelium (carcinoma in-situ) with mitotic figures (arrow), high power




Case #9 - Metastatic Gastrointestinal Stromal Sarcoma

Clinical Summary
50 year old man presented with 2 week history of hematemesis and epigastric pain, and EGD and CT demonstrated a large gastric mass. At surgery he was found to also have a 5 cm liver mass.



Case 9 - Figure 1 - Spindled cell tumor in the liver, low power

Case 9 - Figure 2 - Cellular, spindle cell proliferation of atypical cells, high power

Case 9 - Figure 3 -

Case 9 - Figure 4 - Positive CKit immunostain, high power




Case #10 - Epithelioid Hemangioendothelioma

Clinical Summary
36 year old woman with one tumor in the right lobe and other small nodules in the left lobe. The tumors had white-tan and firm surfaces.



Case 10 - Figure 1 - Nests of atypical cells embedded in a myxohyaline matrix, low power

Case 10 - Figure 2 - Nests and single atypical round cells with a rare intracytoplasmic vacuole containing erythrocytes, high power

Case 10 - Figure 3 - Atypical cells lining vascular spaces, high power

Case 10 - Figure 4 - CD31 immunoreactivity in the atypical cells and lack of staining in admixed benign bile ducts; Cytokeratin postive bile ducts, high power




Case #11 - Hepatoblastoma

Clinical Summary
22 month boy with Down's syndrome, presented with failure to thrive and a large abdominal mass. Abdominal CT scan showed a large hepatic mass.



Case 11 - Figure 1 - Irregular lobules of atypical cells with increased nuclear to cytoplasmic ratio, low power

Case 11 - Figure 2 - Foci of extramedullary hematopoiesis within the sinusoids of the tumor, high power

Case 11 - Figure 3 - Foci of extramedullary hematopoiesis within the sinusoids of the tumor, high power




Case 12 - Embryonal Sarcoma

Clinical Summary
23 year old woman presented with 40 lb unintentional weight loss, abdominal fullness, and non-specific abdominal pain. Abdominal CT demonstrated a hepatic neoplasm, and at surgery, a greater than 10 cm hemorrhagic and necrotic mass was found.



Case 12 - Figure 1 - Proliferation of spindled and stellate cells, low power

Case 12 - Figure 2 - Spindled and stellate cells with ill-defined cell borders and rare multinucleated giant cell, high power

Case 12 - Figure 3 - Epithelioid cells, low power

Case 12 - Figure 4 - Epithelioid atypical cells containing hyaline globules (arrow) within the cytoplasm and stroma, PAS stain with diastase, high power






References
  1. Craig J, Peters R, Edmondson H: Benign tumors and tumor-like conditions. In Hartmann W, Sobin L (eds): Tumors of the Liver and Intrahepatic Bile Ducts. Washington, D.C., Armed Forces Institute of Pathology, 1989, pp 8-98.

  2. Hamazaki K, Mimura H, Orita K, et al: Surgical treatment for hepatocellular carcinoma (HCC) 3 cm or less than 3 cm in diameter. Hepato-Gastroenterology 6:485-588, 1992.

  3. Ishak K, Anthony P, L S: Histological Typing of Tumours of the Liver, 2nd ed. Berlin ,, Springer-Verlag, 1994.

  4. Ljung B, Ferrell L: Fine needle aspiration biopsy of the liver: Diagnostic problems. In Ferrell L (ed): Diagnostic Problems in Liver Pathology. Pathology: State of the Art Reviews. Philadelphia, Hanley & Belfus, Inc, 1994, pp 161-184.

  5. Schoenthaler R, Phillips T, Castro J, et al: Carcinoma of the extrahepatic bile ducts: The University of California at San Francisco experience. Annals of Surgery 219:267-274, 1994.

  6. Torii A, Harada A, Nonami T, et al: Tumor localization as a prognostic factor in hepatocellular carcinoma. Hepato-Gastroenterology 41:16-19, 1994.

  7. Wanless I, Callea F, Craig J, et al: Terminology of nodular lesions of the liver. Hepatology 25:983-993, 1995.

TABLE 1: Classification of Primary Liver Tumors and Tumor-like Lesions From World Health Organization
Epithelial tumors or tumor-like lesions
Benign
 Large regenerative nodule
 Low-grade dysplastic nodule
  High-grade (borderline) dysplastic nodule
  Hepatocellular adenoma
  Focal nodular hyperplasia
 Bile duct adenoma
 Bile duct hamartoma
 Biliary cystadenoma
 Intraductal biliary papillomatosis
 Congenital biliary cysts
 Focal fatty change
Malignant
  Hepatocellular carcinoma, including fibrolamellar variant
  Combined hepatocellular and cholangiolar carcinoma
  Cholangiocarcinoma, peripheral, hilar, and extrahepatic type
  Biliary cystadenocarcinoma
  Intraductal papillary adenocarcinoma
Nonepithelial tumors or tumor-like lesions
Benign
  Hemangioma
 Angiomyolipoma
 Infantile hemangioendothelioma
 Mesenchymal hamartoma
 Localized fibrous tumor
 Solitary necrotic nodule
 Inflammatory pseudotumor
 Infectious cysts
 Other rare benign tumors
Malignant
  Epithelioid hemangioendothelioma
  Angiosarcoma
  Undifferentiated sarcoma (embryonal sarcoma)
 Lymphoma and other hematopoietic tumors
  Kaposi's sarcoma
  Other malignant tumors