Definition/General
Introduction:
Colorectal ganglioneuroma is a rare benign neural tumor composed of mature ganglion cells and nerve fibers
It represents the most mature form of neuroblastic tumors
Most commonly occurs in the rectosigmoid region
Typically presents as a polypoid or submucosal lesion.
Origin:
Originates from neural crest cells
Arises from the enteric nervous system
Composed of mature ganglion cells and supporting Schwann cells
Shows complete neuronal differentiation without immature elements.
Classification:
Classified as mature ganglioneuroma (fully differentiated)
Ganglioneuromatous polyposis (multiple lesions)
Diffuse ganglioneuromatosis (transmural involvement)
Part of neuroblastic tumor spectrum
Associated with MEN 2B syndrome (multiple cases).
Epidemiology:
Peak incidence in childhood and adolescence
Slight male predominance
Most common in rectum and sigmoid colon
Account for <1% of all gastrointestinal tumors
Indian population shows similar age distribution.
Clinical Features
Presentation:
Asymptomatic (many cases)
Constipation (most common)
Abdominal distention
Change in bowel habits
Palpable mass (large lesions)
Intestinal obstruction (rare).
Symptoms:
Chronic constipation (60-70% cases)
Abdominal pain (cramping)
Diarrhea (paradoxical)
Failure to thrive (children)
Hirschsprung-like symptoms
Bowel perforation (rare).
Risk Factors:
MEN 2B syndrome (increased risk)
Neurofibromatosis type 1
Cowden syndrome
Genetic predisposition
RET gene mutations.
Screening:
Colonoscopy for detection
Barium enema (historical)
CT colonography
Genetic counseling (syndromic cases)
Family screening (MEN 2B).
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Gross Description
Appearance:
Polypoid or nodular lesions
Firm consistency
Gray-white cut surface
May show multinodular pattern
Mucosal ulceration may be present over large lesions.
Characteristics:
Well-demarcated but unencapsulated
Homogeneous gray-white appearance
Cut surface shows fascicular pattern
No necrosis or hemorrhage
Firm to rubbery consistency.
Size Location:
Size ranges from 0.5-10 cm
Rectum (50-60% cases)
Sigmoid colon (20-30% cases)
Pan-colonic involvement (ganglioneuromatous polyposis)
Transmural extension possible.
Multifocality:
Usually solitary
Multiple lesions in polyposis syndromes
Ganglioneuromatous polyposis (>20 polyps)
Diffuse ganglioneuromatosis (transmural)
Associated with MEN 2B syndrome.
Microscopic Description
Histological Features:
Mature ganglion cells scattered in fibrous stroma
Nerve bundles and Schwann cells
Satellite cells around ganglion cells
Abundant neuropil
No immature elements.
Cellular Characteristics:
Large ganglion cells with abundant eosinophilic cytoplasm
Large vesicular nuclei with prominent nucleoli
Nissl substance in cytoplasm
Multipolar processes
Binucleate forms common.
Architectural Patterns:
Haphazard arrangement of ganglion cells
Fibrous stroma with nerve bundles
Spindle cell component (Schwann cells)
Mucosal involvement in polypoid lesions
Transmural pattern in diffuse type.
Grading Criteria:
Benign tumor (no grading)
Mature differentiation (key feature)
Absence of mitoses
No cellular atypia
No immature elements (neuroblasts).
Immunohistochemistry
Positive Markers:
Synaptophysin (ganglion cells positive)
Neurofilament (strong positive)
NeuN (neuronal nuclei)
S-100 protein (Schwann cells)
GFAP (glial elements).
Negative Markers:
Chromogranin A (usually negative)
CD117 (negative)
CD34 (negative)
Smooth muscle actin (negative)
Desmin (negative).
Diagnostic Utility:
Synaptophysin positivity confirms neural differentiation
Neurofilament highlights neural processes
S-100 identifies Schwann cell component
NeuN positivity confirms mature neurons
Combined pattern diagnostic.
Molecular Subtypes:
Sporadic type (most common)
MEN 2B-associated (RET mutations)
NF1-associated (neurofibromatosis)
Cowden syndrome-associated (PTEN mutations)
Familial clustering reported.
Molecular/Genetic
Genetic Mutations:
RET gene mutations (MEN 2B syndrome)
NF1 gene mutations (neurofibromatosis)
PTEN mutations (Cowden syndrome)
Sporadic mutations (most cases)
1p36 deletions (some cases).
Molecular Markers:
Synaptophysin expression (ganglion cells)
Neurofilament protein (neural processes)
S-100 protein (Schwann cells)
GFAP expression (glial elements)
Neurotrophin receptors.
Prognostic Significance:
Excellent prognosis (benign tumor)
Complete excision curative
No malignant potential
MEN 2B association requires screening
Functional bowel symptoms may persist.
Therapeutic Targets:
Surgical excision (treatment of choice)
Endoscopic resection (small lesions)
Symptomatic management (constipation)
Genetic counseling (syndromic cases)
Family screening (hereditary syndromes).
Differential Diagnosis
Similar Entities:
Ganglioneuroblastoma (immature elements present)
Paraganglioma (neuroendocrine tumor)
Schwannoma (pure Schwann cell tumor)
Neurofibroma (mixed neural tumor)
Inflammatory fibroid polyp.
Distinguishing Features:
Ganglioneuroma: Mature ganglion cells
Ganglioneuroma: No immature elements
Ganglioneuroblastoma: Neuroblasts present
Paraganglioma: Chromogranin positive
Schwannoma: S-100 positive only
Neurofibroma: CD34 positive.
Diagnostic Challenges:
Distinguishing from ganglioneuroblastoma (immature elements)
Differentiating from paraganglioma (chromogranin)
Identifying syndromic associations
Recognizing polyposis patterns
Adequate sampling important.
Rare Variants:
Ganglioneuromatous polyposis (multiple lesions)
Diffuse ganglioneuromatosis (transmural)
MEN 2B-associated (mucosal neuromas)
Composite tumors (mixed elements)
Myenteric plexus hyperplasia.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
Ganglioneuroma
Location
Location: [anatomical site in colorectum]
Histological Features
Shows mature ganglion cells scattered in fibrous stroma with nerve bundles and Schwann cells. No immature neuroblastic elements identified.
Size and Extent
Size: [X] cm, well-demarcated lesion
Cellular Features
Large ganglion cells with abundant eosinophilic cytoplasm, vesicular nuclei and prominent nucleoli. Schwann cells and nerve bundles present.
Immunohistochemistry
Synaptophysin: Positive (ganglion cells)
Neurofilament: Positive (neural processes)
S-100 protein: Positive (Schwann cells)
Chromogranin A: Negative
Maturity Assessment
Complete neuronal maturation with no immature neuroblastic elements
Final Diagnosis
Colorectal Ganglioneuroma - Benign mature neural tumor