What are submucosal or subepithelial lesions?

Imagine the digestive tract (esophagus, stomach, intestine) as a multi-layered tube. The innermost layer is called the mucosa and is what we see directly with the endoscope. Beneath it are the submucosa and muscle layer.

A submucosal or subepithelial lesion is a "bump" that originates beneath the mucosa. From the outside, it looks like an elevation covered by normal mucosa (without ulceration, without striking color change), but the endoscopist notices it's "not a classic polyp": it's firmer, deeper, as if something underneath is pushing toward the lumen. ¹

Most common types (mostly benign)

The "classic benign ones"

Lipomas: fat accumulations beneath the mucosa, very common in the right colon. They're soft, hyperechoic on endoscopic ultrasound, and require no treatment unless they cause symptoms (extremely rare). ⁴

Leiomyomas: smooth muscle tumors, typical in the esophagus. They appear as firm, well-defined lesions, and in the esophagus are almost always benign (esophageal GISTs are exceptional, <1%). ^{5 6}

Cysts, ectopic pancreas, granular cell tumors, schwannomas: rare lesions but usually benign, identified with endoscopic ultrasound and, if necessary, biopsy. ⁷

Those that need monitoring or resection

GIST (gastrointestinal stromal tumor): the best-known one with malignant potential. Typical of the stomach, though it can appear anywhere. Small GISTs (<2 cm) without aggressive features can be monitored; large ones or those with risk characteristics are resected. ^{8 9}

Neuroendocrine tumors (NET): common in rectum and stomach. Small ones (<10 mm, well-differentiated) in the rectum can be resected via mucosal resection (EMR) with excellent results. Larger ones or those with aggressive criteria require more complete study. ^{10 11}

Lesions in esophagus and stomach: what to expect?

Esophagus

The vast majority of esophageal subepithelial lesions are benign leiomyomas. They're hard, well-defined, and grow from the muscle layer. Esophageal GIST is extremely rare (<1% of all GISTs). ^{5 12}

If a leiomyoma is large (>3–5 cm) or causes symptoms (dysphagia, pain), it can be resected using advanced endoscopy techniques like STER (submucosal tunneling endoscopic resection) or EFTR (endoscopic full-thickness resection), with very high success rates and few complications. ^{13 14}

Stomach

Here things are more varied: lipomas, ectopic pancreas, neuroendocrine tumors, leiomyomas… and GIST. Endoscopic ultrasound (EUS) is key to distinguishing them: it measures size, sees the layer of origin, detects echogenicity (lipomas are very bright, GISTs are usually hypoechoic). ^{8 15}

Guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and the American College of Gastroenterology (ACG) agree: small gastric lesions (<1–2 cm), without alarm signs, can be monitored with follow-up endoscopies. If they grow, they're resected. ^{16 17}

Lesions in colon and rectum: increasingly common findings

With increased screening colonoscopies, more colonic subepithelial lesions are being detected. The good news: most are lipomas, lymphangiomas, inflammatory polyps, or even retained fecaliths (which can be mistaken for tumors). ^{4 18}

In a series of 105 colorectal subepithelial lesions, only 2.9% were malignant, and all "soft" lesions on endoscopic palpation were benign. ²

Lesions requiring monitoring are: rectal neuroendocrine tumors (common, but most small and low-grade), colorectal GISTs (rare), and occasionally lymphomas or metastases. ^{10 19}

When to study thoroughly (and when monitoring is sufficient)?

If your lesion is small (<1 cm), soft, without mucosal changes, and endoscopic ultrasound shows a well-defined lipoma or leiomyoma… you can rest easy. In long-term follow-up studies, these lesions almost never grow or cause problems. ^{3 20}

The key role of endoscopic ultrasound (EUS)

Endoscopic ultrasound is like doing an "ultrasound from inside" the digestive tract. It tells us:

• Which layer the lesion originates from (mucosa, submucosa, muscle…).
• Whether it's solid, cystic, or fatty (hyperechoic → lipoma; hypoechoic → GIST, NET, leiomyoma).
• Exact size (often more precise than endoscopy).
• If needed, guides fine-needle aspiration/biopsy (FNA/FNB) to obtain tissue for histological diagnosis. ^{8 21}

In my daily practice, EUS is the test that "puts a name" to the lesion and decides whether we monitor, resect, or request further studies.

Treatment options: advanced endoscopy vs surgery

Years ago, many submucosal lesions were operated on with open or laparoscopic surgery. Today, most can be resected endoscopically, thanks to techniques like:

Mucosal resection (EMR)

For small, superficial lesions (mucosa + superficial submucosa). Very useful in rectal neuroendocrine tumors <10 mm or polyps with submucosal component. ²² More info: Endoscopic Mucosal Resection (EMR).

Endoscopic submucosal dissection (ESD)

The gold standard technique for large mucosal/submucosal lesions. Allows en bloc resection, clear margins, and complete analysis. In my experience, it's the technique of choice for large colorectal polyps with suspected submucosal invasion. ²³ More info: Endoscopic Submucosal Dissection (ESD).

STER, EFTR, tunneling resection

For lesions originating in the muscle layer (esophageal leiomyomas, some small GISTs): a submucosal "tunnel" is created, the tumor is reached, resected, and closed. Excellent results in referral centers. ^{13 14}

In a recent review of endoscopic resections of colorectal subepithelial lesions, en bloc resection was achieved in ~97% and complete resection in ~89%, with low complication rates (perforation <5%, controllable bleeding). ³

What you can do starting today?

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FAQ: quick questions about submucosal lesions