Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging
of human tissues at a depth of 60–70 μm during endoscopy. pCLE of the
extrahepatic bile duct after fluorescein injection demonstrated a reticular
pattern within fluorescein-filled sinuses that had no known anatomical
correlate. Freezing biopsy tissue before fixation preserved the anatomy of
this structure, demonstrating that it is part of the submucosa and a
previously unappreciated fluid-filled interstitial space, draining to lymph
nodes and supported by a complex network of thick collagen bundles. These
bundles are intermittently lined on one side by fibroblast-like cells that
stain with endothelial markers and vimentin, although there is a highly
unusual and extensive unlined interface between the matrix proteins of the
bundles and the surrounding fluid. We observed similar structures in
numerous tissues that are subject to intermittent or rhythmic compression,
including the submucosae of the entire gastrointestinal tract and urinary
bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and
fascia. These anatomic structures may be important in cancer metastasis,
edema, fibrosis, and mechanical functioning of many or all tissues and
organs. In sum, we describe the anatomy and histology of a previously
unrecognized, though widespread, macroscopic, fluid-filled space within and
between tissues, a novel expansion and specification of the concept of the
human interstitium.

Benias, P. C., Wells, R. G., Sackey-Aboagye, B., Klavan, H., Reidy, J.,
Buonocore, D., … Theise, N. D. (2018). Structure and Distribution of an
Unrecognized Interstitium in Human Tissues. Scientific Reports, 8(1), 4947.
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