Myofibroblasts in focal nodular hyperplasia of the liver.

ABSTRACT

Myofibroblasts have been identified by electron microscopy in a case of Focal Nodular Hyperplasia (FNH) of the liver associated with oral contraceptives. The contractile fibroblasts were observed in the immediate vicinity of, or in close contact with, the proliferating bile ductules and in the recesses between parenchymal cells. Transitional forms between fat-storing cells (Ito cells), fibroblasts and myofribroblasts were observed. Transition of fat-storing cells to myofibroblasts, possibly under the influence of oestrogens, may be responsible for the fibrosis and retraction in FNH.

ABSTRACT

PIP The purpose of this discussion is to document the finding of contractile fibroblasts and to examine their possible origin in a further pathological process focal nodular hyperplasia (FNH) of the liver. A 31-year old female patient underwent laparotomy for a hypochondrial mass. The patient had been taking OCs for 1 year. The mass was located in the right lobe of the liver and excision of the tumor was performed. Some distance from it a subcapsular hemangioma was discovered and resected. After 16 months of follow-up the patient is well. The tumor mass (10 cm diameter) grey in color, was very well demarcated, although not encapsulated. A central scar was present. Radiating septa divided the periphery of the mass into multiple, variable sized modules, simulating a pattern of focal cirrhosis. No areas of hemmorhage or infraction were observed. The hemangioma specimens showed multiple cyst-like cavities filled with blood. The bosselated and lobulated appearance was because of areas of fibrosis, which was most marked centrally. Vascular changes similar to those described by Mays et al. and bile ductular proliferation analogous to that described by others were seen. Single small bile ductules were frequently observed within parenchymal nodules, without any relation to the intranodular scars. Cells with elongated, cross banded nuclei were in close vicinity of the newly formed ductules. Inflammatory and fibroblast-like cells were seen in the fibrous connective tissue septa. The 2nd lesion showed the typical features of a cavernous hemangioma. Typical fibroblasts were identified by their elongated or star-like shape, the slender fusiform shape and relatively smooth outline of the nucleus, the well developed RER and Golgi apparatus, the scattered mitochondria, and the absence or scanty presence of cytofilaments. A large number of elongated cells exhibited the characteristic morphology of modified contractile fibroblasts (MF). They showed a variable amount of intracytoplasmic microfilaments, arranged in longitudinal bundles, usually parallel to the long axis of the cell predominantly located beneath the plasma membrane. Intracellular connections between modified fibroblasts were frequently observed; they were mostly of the macula-adherens type. The finding of contractile fibroblasts raises questions concerning the origin and the significance of such cells in FNH. Since MFs are similar to both fibroblasts and smooth muscle cells, it seemed reasonable to conclude that both cells, under appropriate conditions, may become MF. Fat storing cells of Ito may also be a progenitor of contractile fibroblasts.