Ganglioneuroma of the Gastrointestinal Tract

Definition

• Gastrointestinal polyp composed of S100 positive spindled cells and ganglion cells

Note

• Ganglioneuroma of the GI tract has nothing to do with the lesion of the same name occurring in the adrenal and related tissues that is part of the neuroblastoma spectrum

Diagnostic Criteria

• Lamina propria expanded by an infiltrate of spindled cells and ganglion cells
• Indistinct borders
• Spindled cells in a fibrillar matrix surround crypts
• No atypia or mitotic activity
• Varying numbers of ganglion cells
• May be immature
• Nuclei smaller and nucleoli less prominent
• May range from rare to nodular collections
• Eosinophils may be frequent
• Extensively S100 positive spindled cells
• Neurofilament may highlight ganglion cells and multiple axons
• Surrounded crypts may be distorted and cystic
• May resemble juvenile polyps
• Plexiform pattern seen in some cases
• Involves mucosa and submucosa
• Nearly all occur in the colorectum
• Most endoscopically biopsied lesions are a few mm in size
• Can be as large as 3 cm
• When solitary:
• No relationship to familial syndromes
• Benign
• No recurrence
• Similar non-solitary lesions associated with syndromes
• Ganglioneuromatous polyposis
• Multiple ganglioneuromas similar to above
• Usually 20 to innumerable
• May be more polymorphous
• May have villous surface
• Frequently reported with associated peripheral and GI lipomas
• May be associated with PTEN Hamartomatous Tumor syndrome (unified syndrome including Cowden Disease and Bannayan-Ruvalcaba-Riley syndrome)
• Cutaneous lesions of PHTS other than lipoma have not been described, however
• Diffuse ganglioneuromatosis
• Poorly demarcated nodular or diffuse involvement of a bowel segment by a mixture of spindled and ganglion cells
• Frequently transmural
• Most often involves region of terminal ileum, appendix and cecum
• Associated with MEN2b and NF1

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

Original posting/updates : 11/29/09, 11/13/11

Differential Diagnosis

Distinction between normal ganglion cells overrun by a nerve sheath neoplasm and those intrinsic to ganglioneuroma

• Ganglion cells are not normally present in the lamina propria
  • Ganglion cells in ganglioneuroma may be immature
• Smaller nuclei and nucleoli

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 Ganglioneuroma
No ganglion cells	Contains ganglion cells
Most cases intramural	Predominantly lamina propria
Peripheral lymphoid cuff common	Lacks lymphoid cuff

GI Ganglioneuroma	GI Neurofibroma
Ganglion cells present	Lacks ganglion cells

GI Ganglioneuroma	GI Perineurioma
Ganglion cells present	No ganglion cells
S100 100%	S100 negative
Perineurial markers negative	Perineurial markers positive

Bibliography

• Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010.
• Shekitka KM, Sobin LH. Ganglioneuromas of the gastrointestinal tract. Relation to Von Recklinghausen disease and other multiple tumor syndromes. Am J Surg Pathol. 1994 Mar;18(3):250-7.
• Grobmyer SR, Guillem JG, O'Riordain DS, Woodruff JM, Shriver C, Brennan MF. Colonic manifestations of multiple endocrine neoplasia type 2B: report of four cases. Dis Colon Rectum. 1999 Sep;42(9):1216-9.
• Lashner BA, Riddell RH, Winans CS. Ganglioneuromatosis of the colon and extensive glycogenic acanthosis in Cowden's disease. Dig Dis Sci. 1986 Feb;31(2):213-6. (Note: the description of the colorectal lesion in this report fits better with ganglioneuromatous polyposis than with diffuse ganglioneuromatosis)