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.

First, a quick clarification: reticulin fibers are actually collagen fibers (specifically, they are type III collagen fibers). So the terms “reticulin fibrosis” and “collagen fibrosis” are a little confusing (since they both refer to an excess of collagen fibers). However, when you hear/read the word “collagen” without any other descriptor (e.g., type I collagen, type II collagen, type III collagen etc.), the implication is often that the collagen in question is type I collagen (probably because that’s the most abundant type of collagen in the body).

Okay, on to the differences between these terms.

Reticulin fibrosis means that you have an excess of type III collagen fibers (also called reticulin fibers). Reticulin fibers are so thin that they are invisible on regular hematoxylin and eosin (H&E) stains. To see them, you need to do 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 means that you have an excess of type I collagen. Type I collagen looks like thick, pink bundles of fibers on H&E staining. You can also use something called a trichrome stain, which stains type I collagen fibers a pretty light blue color (see above right). Unlike reticulin fibers, type I collagen fibers are not seen in normal bone marrow biopsies. The most common settings in which you see type I collagen fibers in the bone marrow are chronic myelofibrosis (a type of myeloproliferative disorder) and metastatic tumor. Fibrosis is a fairly common finding in and around tumor cells in general; this is called a “desmoplastic reaction.”

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.