Definition/General
Introduction:
Splenic hamartoma is a rare benign tumor-like lesion composed of disorganized but mature splenic tissue
It represents the second most common primary benign tumor of the spleen after hemangioma
Hamartomas are developmental anomalies rather than true neoplasms, consisting of normal tissue components in abnormal proportions or arrangements
Most are asymptomatic and discovered incidentally.
Origin:
Arises from aberrant development of splenic tissue during embryogenesis
Results from excessive proliferation of one or more normal splenic components
Most commonly involves red pulp elements including sinusoids, cords, and macrophages
White pulp hamartomas are extremely rare
Represents localized overgrowth rather than neoplastic transformation.
Classification:
Histologic types: Red pulp hamartoma (>95% of cases)
White pulp hamartoma (rare)
Mixed type (very rare)
By size: Small (<2 cm)
Medium (2-5 cm)
Large (>5 cm)
By number: Solitary (typical)
Multiple (rare, associated with syndromes).
Epidemiology:
Rare lesions: <200 cases reported in literature
Age distribution: Wide range (3-80 years), median age 45-50 years
Gender: Equal male-female distribution
Association: Rare association with tuberous sclerosis
Geographic distribution: No specific geographic predilection.
Clinical Features
Presentation:
Asymptomatic in majority (60-70%) of patients
Left upper quadrant pain most common symptom when present
Splenomegaly if lesion is large
Palpable mass in some cases
Constitutional symptoms rare unless very large
Hypersplenism uncommon.
Symptoms:
Abdominal symptoms: Vague left upper quadrant discomfort
Early satiety if mass effect present
Systemic symptoms: Usually absent
Fatigue in rare cases with hypersplenism
Acute symptoms: Very rare rupture with hemorrhage
No B-symptoms (fever, night sweats, weight loss).
Risk Factors:
Developmental factors: Congenital developmental anomaly
Genetic syndromes: Rare association with tuberous sclerosis complex
Family history: Usually sporadic, rare familial cases
No known environmental factors associated with development.
Screening:
Incidental detection on routine imaging (CT, MRI, ultrasound)
Imaging characteristics: Well-circumscribed mass with variable enhancement
Differential diagnosis includes other benign and malignant splenic lesions
Tissue diagnosis often required for definitive classification.
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Gross Description
Appearance:
Well-demarcated, nodular lesion with smooth or slightly lobulated contour
Red-brown to dark red color similar to normal red pulp
Soft, spongy consistency resembling normal spleen
Homogeneous cut surface without necrosis or hemorrhage
No true capsule but well-demarcated from surrounding tissue.
Characteristics:
Size range: 0.5-17 cm (average 3-5 cm)
Solid lesion without cystic areas
Uniform consistency throughout
Absence of calcification in typical cases
No areas of necrosis unless complicated
Resembles splenic tissue grossly.
Size Location:
Location: Any part of spleen, no specific predilection
Well-circumscribed borders distinguish from normal spleen
Single lesion in vast majority of cases
Subcapsular location in some cases allows enucleation
Size correlation: Larger lesions more likely symptomatic.
Multifocality:
Solitary lesions in >95% of cases
Multiple hamartomas extremely rare, may suggest syndrome association
No associated lymphadenopathy
Surrounding spleen typically normal
Rare bilateral involvement reported in syndromic cases.
Microscopic Description
Histological Features:
Disorganized red pulp architecture with dilated sinusoids and splenic cords
Increased CD68-positive macrophages throughout the lesion
Absent or rudimentary white pulp structures
Proliferation of endothelial-lined spaces
Normal cellular maturation without atypia.
Cellular Characteristics:
Normal cellular components: No cytologic atypia or increased mitotic activity
Macrophages: Abundant CD68+ macrophages with normal morphology
Endothelial cells: Lining dilated sinusoidal spaces
Fibroblasts: Minimal fibrous tissue
Plasma cells and lymphocytes: Scattered inflammatory cells.
Architectural Patterns:
Red pulp predominance: Expanded red pulp with dilated sinusoids
Disorganized architecture: Loss of normal splenic organization
Absent follicular structures: No germinal centers or mantle zones
Sinusoidal dilatation: Prominent dilated vascular spaces
Cord expansion: Thickened splenic cords.
Grading Criteria:
Benign lesion: No grading system applicable
Cellular maturity: All components show mature morphology
Absence of atypia: No nuclear pleomorphism or abnormal mitoses
No malignant potential: Entirely benign developmental lesion.
Immunohistochemistry
Positive Markers:
Macrophage markers: CD68 strongly positive in abundant macrophages
Endothelial markers: CD31, CD34 positive in sinusoidal lining
Red pulp markers: Markers of normal red pulp function
Vascular markers: Factor VIII in endothelial cells.
Negative Markers:
White pulp markers: CD20, CD3 typically absent or minimal
Follicular markers: CD21, CD23 negative (absent follicular dendritic cells)
Epithelial markers: Cytokeratins negative
Neuroendocrine markers: Chromogranin, synaptophysin negative.
Diagnostic Utility:
Confirmation of hamartomatous nature: Normal tissue components in abnormal arrangement
Red pulp confirmation: CD68+ macrophages predominant
Vascular nature: Endothelial markers highlight architecture
Exclusion of malignancy: Normal immunoprofile without aberrant expression.
Molecular Subtypes:
Red pulp hamartoma: CD68+ macrophage-rich lesion
Vascular-predominant: Prominent endothelial markers
Mixed type: Variable expression of different splenic components
Associated syndrome cases: May have additional genetic markers.
Molecular/Genetic
Genetic Mutations:
Developmental genes: Alterations in splenic development pathways (theoretical)
TSC genes: TSC1/TSC2 mutations in tuberous sclerosis-associated cases
Angiogenesis genes: Possible alterations in vascular development
Generally normal karyotype: No consistent chromosomal abnormalities.
Molecular Markers:
Developmental markers: Expression of embryonic splenic development genes
Angiogenesis factors: VEGF, angiopoietins in vascular components
Macrophage function markers: Normal macrophage activation markers
Proliferation markers: Ki-67 typically very low.
Prognostic Significance:
Excellent prognosis: Benign lesions with no malignant potential
No recurrence: Complete excision is curative
Size-related symptoms: Large lesions may cause discomfort
Syndrome association: May indicate need for genetic evaluation.
Therapeutic Targets:
Conservative management: Observation for small asymptomatic lesions
Surgical options: Enucleation preferred over splenectomy when possible
No medical therapy: No role for pharmacologic treatment
Long-term follow-up: Usually not required after complete excision.
Differential Diagnosis
Similar Entities:
Splenic hemangioma: Vascular tumor with different architecture
Littoral cell angioma: Different immunoprofile and morphology
Accessory spleen: Normal splenic architecture with white and red pulp
Splenic lymphoma: Malignant with monoclonal population
Inflammatory pseudotumor: More inflammatory, different immunoprofile.
Distinguishing Features:
Hamartoma vs hemangioma: Macrophage-rich vs purely vascular
CD68+ vs CD68-
Hamartoma vs accessory spleen: Disorganized vs normal architecture
Absent vs present white pulp
Hamartoma vs lymphoma: Polyclonal vs monoclonal
Normal vs atypical cells
Immunohistochemistry crucial for differentiation.
Diagnostic Challenges:
Small lesions: May be difficult to distinguish from normal spleen
Vascular-rich areas: May mimic hemangioma
Inflammatory infiltrate: May suggest reactive process
Lack of white pulp: May be concerning for malignancy
Needle biopsy interpretation: May be difficult on small samples.
Rare Variants:
White pulp hamartoma: Predominantly lymphoid tissue (extremely rare)
Mixed hamartoma: Both red and white pulp components
Calcified hamartoma: Rare dystrophic calcification
Syndrome-associated: Multiple hamartomas in tuberous sclerosis
Pediatric hamartomas: May have different morphologic features.
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
[Enucleation/splenectomy] specimen with [clinical presentation] and imaging showing [mass characteristics]
Gross Description
Well-demarcated nodular lesion measuring [dimensions] with [red-brown color] and [spongy consistency]
Microscopic Findings
Disorganized red pulp architecture with [dilated sinusoids], [abundant macrophages], and [absent white pulp]
Immunohistochemical Studies
CD68 strongly positive in abundant macrophages. CD31/CD34 positive in sinusoidal endothelium
Diagnosis
Splenic hamartoma (red pulp type), measuring [size]
Classification
Benign developmental lesion with no malignant potential
Excision Status
[Complete/incomplete] excision with [clear/involved] margins
Prognosis
Excellent prognosis. Complete excision is curative with no risk of recurrence