Hepatocellular dysplastic nodules

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Massimo Roncalli, Mauro Borzio, Luca Di Tommaso

Ann. Ital. Chir., 2008; 79: 81-89

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The multistep process of hepatic carcinogenesis is mirrored by the morphologic classification of lesions detectable in cirrhosis,
that include large regenerative nodules (LRN), low grade dysplastic nodules (LGDN) and high grade dysplastic
nodules (HGDN). The latter belong to the “bordeline malignancy” cathegory requiring an accurate distinction from welldifferentiated
and early hepatocellular carcinoma. Nodules in cirrhosis are usually detected by non-invasive imaging techniques,
being the latter unable to discriminate malignant from non-malignant forms, particularly in the 1-2 cm sized
group. Liver biopsy is essential in providing practical diagnostic information to hepathologists in the management of cirrhotic
patients with US detectable nodules. The histologic diagnosis on liver samples is based on the accurate search of
a set of cyto-architectural features (cell atypia, cell crowding, trabecular thickness, microacini etc) and by a supplement
of histochemical (Gomori staining) and immunocytochemical stainings. The latter rely upon the search of both well established
and novel markers, targeted to evaluate stromal invasion (CK7/19), the vascular pattern (ASMA and CD34)
or tumor markers (HSP70 and Glipican 3 among others). Still, the diagnostic sensitivity is limited by the type and size
of sampling and by its representativity of the entire lesion. The best diagnostic approach thus requires the integration of
clinical, morphological and immunocytochemical information with imaging data (US pattern, perfusional pattern, helical
CT/MR pattern). Molecular data are still under evaluation as to their diagnostic efficacy in this controversial field.
Discrepancies have emerged recently between Eastern and Western interpretation of these lesions, particularly in the cathegory
of “borderline” nodules, that are mostly labelled as early, well differentiated HCC by eastern pathologists and as
HGDN by western pathologists. Novel and more objective phenotypical and molecular markers are needed to discriminate
within the grey area of borderline lesions that, epidemiologically, are likely distinct between eastern and western
geographic areas. These tools might allow a better understanding of the boundaries of the process going from high grade
dysplasia to in situ HCC and from the latter to microinvasive HCC and advanced HCC, for a proper clinical management
and optimal therapy.

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