Mucosal Benign Epithelioid Nerve Sheath Tumor

Definition

• Intramucosal infiltrate of S100 positive epithelioid cells lacking other neural elements

Diagnostic Criteria

• Lamina propria expanded by an infiltrate of epithelioid cells in 5/6 cases
• At least some cases have a spindled component
• Some extend into superficial submucosa
• One case entirely submucosal
• Pushing to infiltrating borders in 5/6 cases
• Surrounds and entraps crypts
• 1/6 cases encapsulated
• Uniform bland epithelioid cells
• Eosinophilic cytoplasm
• Uniform round to ovoid nuclei
• No atypia, pleomorphism or mitotic activity
• Frequent intranuclear pseudoinclusions
• No ganglion cells or axons in lesion
• No surrounding lymphoid cuff
• Extensively S100 positive
• CD34 positive in 3/5, described as supporting cells or lesional cells
• Illustration appears to show lesional cells stained
• Negative for CD117, calretinin, EMA
• Soft tissue schwannomas usually calretinin positive
• Only one case tested for EMA
• No axons on SM31 (neurofilament) stain
• All reported GI cases occur in the colorectum
• Most are distal
• 2-10 mm in size
• No relationship to familial syndromes
• Benign
• No recurrence
• At least one case of microcystic/reticular schwannoma reported by Liegl might be included in this group
  • 1/5 cases reported was intramucosal

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : November 29, 2009

Differential Diagnosis

• Schwannoma
• Neurofibroma
• Perineurioma
• Epithelioid leiomyoma
• Epithelioid GIST

Mucosal Benign Epithelioid Nerve Sheath Tumor	Mucosal Schwann Cell Hamartoma	GI Ganglioneuroma
Epithelioid	Spindled	Spindled
No axons	Very rare axons	Axons present
No ganglion cells	No ganglion cells	Ganglion cells present

It is possible that Mucosal Benign Epithelioid Nerve Sheath Tumor and Mucosal Schwann Cell Hamartoma are related

GI Schwannoma	GI Mucosal Benign Epithelioid Nerve Sheath Tumor
Most cases intramural	Most cases confined to lamina propria
Peripheral lymphoid cuff common	Lacks lymphoid cuff
Frequent pleomorphic hyperchromatic cells	No pleomorphism
Spindled cells	Epithelioid cells

GI Mucosal Benign Epithelioid Nerve Sheath Tumor	GI Neurofibroma
Axons absent	Axons scattered throughout
Very uniform infiltrate	More heterogeneity in infiltrate
Restricted to colon	Most are in stomach and small intestine
Epithelioid cells	Spindled cells

GI Mucosal Benign Epithelioid Nerve Sheath Tumor	GI Perineurioma
Abundant cytoplasm	Scant cytoplasm
No association with hyperplastic crypts	Frequently associated with hyperplastic crypts
Perineurial markers negative	Perineurial markers positive
S100 positive	S100 negative
Epithelioid cells	Spindled cells

GI Mucosal Benign Epithelioid Nerve Sheath Tumor	GI Leiomyoma (Epithelioid)
Most in lamina propria	Most colonic lesions centered on muscularis mucosae
S100 positive	S100 negative
Smooth muscle actin negative	Smooth muscle actin positive
Restricted to colon	Very rare in intestines

Most epithelioid leiomyomas reported in the past are now considered GIST

GI Mucosal Benign Epithelioid Nerve Sheath Tumor	GIST (Epithelioid)
Centered in lamina propria or submucosa	Most centered on muscularis propria
S100 positive	S100 negative
CD117 negative	CD117 74-95%
CD34 negative	CD34 70%
Restricted to colon	Most common in stomach

Bibliography

• Liegl B, Bennett MW, Fletcher CD. Microcystic/reticular schwannoma: a distinct variant with predilection for visceral locations. Am J Surg Pathol. 2008 Jul;32(7):1080-7.
• Lewin MR, Dilworth HP, Abu Alfa AK, Epstein JI, Montgomery E. Mucosal benign epithelioid nerve sheath tumors. Am J Surg Pathol. 2005 Oct;29(10):1310-5.