Q.  What is the difference between reticulin fibrosis and collagen fibrosis (the two terms used in the WHO criteria for grading myelofibrosis)?

A. Reticulin fibrosis and collagen fibrosis are indeed two different things, with different implications.

Reticulin fibrosis is best seen with – not surprisingly – a reticulin stain (which contains silver). In this stain, reticulin fibers look like thin, wavy black lines (above left). Normal bone marrow contains some reticulin fibers; they are scattered and individual (not dense or overlapping). Reticulin fibrosis is also present in a bunch of different benign and malignant disorders.

Collagen fibrosis is best seen on a trichrome stain. In this type of fibrosis, the fibers are composed of type I collagen, and they stain bluish-green (above right). Unlike reticulin fibrosis, collagen fibrosis is not seen in normal bone marrow biopsies. It’s often present in  myeloproliferative disorders (particularly in the end stages), and it can also be seen in areas of tumor metastasis to the bone marrow.

The amount of reticulin fibrosis doesn’t really correlate with the severity of the particular disease. The amount of collagen fibrosis, however, is correlated with the severity of the disease – the more you have, the more severe the disease and the worse the prognosis.