Histological studyAnnals of Anatomy2026Free article

Absence of interstitial cells of Cajal in human colonic muscularis mucosae

A retrospective immunohistochemical study concluding that the human colonic muscularis mucosae lacks demonstrable interstitial cells of Cajal, suggesting that mucosal motility is regulated more directly by neural mechanisms than by ICC-mediated pacemaker activity.

Mugurel Constantin Rusu · Daniel-Nicolae Pirici · Ivan Varga · Mihnea Ioan Nicolescu
The key conclusion

No convincing ICC-MM were found in the examined human colonic specimens.

Across archived paraffin-embedded colon material stained with c-kit/CD117 and CD31, the study identified c-kit-positive mast cells but no spindle-shaped, stellate, or polygonal ICC-like cells in the muscularis mucosae.

15archived human colon specimens examined histologically
01 · Study design

Focused on the muscularis mucosae

The study specifically addressed a poorly explored question: whether ICC are present in the lamina muscularis mucosae of the human colon, rather than in the much better-studied tunica muscularis.

15

Specimens

Archived paraffin-embedded human colon samples.

2

Primary markers

CD117/c-kit and CD31 were used.

0

ICC-MM found

No distinct ICC in the muscularis mucosae were demonstrated.

Present

Mast cells

Scattered c-kit-positive mast cells were observed instead.

02 · Main finding

Positive c-kit staining was not enough

The study emphasises that c-kit positivity alone cannot establish ICC identity. Morphology and distribution were decisive in distinguishing mast cells from true interstitial cells of Cajal.

Expected ICC-MMspindle / stellate / polygonalnot observedObserved c-kit-positive cellsround-to-oval cells with granular cytoplasminterpreted as mast cells
Interpretive point: the paper stresses that c-kit-positive cells in the mucosa should not be labelled ICC automatically. Their round-to-oval shape and perivascular distribution supported mast-cell identification.
03 · Implications

What the negative finding changes conceptually

If the human colonic muscularis mucosae lacks ICC-MM, then mucosal motility may rely more on direct neural innervation than on canonical ICC-mediated pacemaker networks described in other gastrointestinal layers.

01

A distinct motor layer

The muscularis mucosae should not be assumed to behave like the tunica muscularis, where ICC are well established.

02

Functional bowel disorders

The finding may help explain why therapies or concepts centred on ICC dysfunction do not necessarily extrapolate cleanly to mucosal motility disorders.

03

Histological caution

The paper provides a methodological reminder that marker positivity must be interpreted together with morphology and topography.

Take-home message: the human colonic muscularis mucosae appears to represent a distinct therapeutic and physiological target, potentially governed by direct neural control rather than ICC-mediated pacing.