Definition/General
Introduction:
Splenic littoral cell angioma (LCA) is a rare benign vascular tumor unique to the spleen, first described in 1991
It arises from the littoral cells that line the splenic red pulp sinusoids
These cells have dual endothelial and histiocytic properties
LCA accounts for less than 1% of all splenic lesions and represents a distinctive primary splenic neoplasm with characteristic morphologic and immunohistochemical features.
Origin:
Originates from littoral cells of splenic sinusoids which are specialized cells lining the red pulp sinusoidal spaces
These cells have unique phenotypic characteristics expressing both endothelial and macrophage markers
Neoplastic transformation of these cells results in vascular proliferation
The exact etiology is unknown but may be related to immune dysfunction.
Classification:
Histologic pattern: Anastomosing vascular channels lined by prominent cells
By behavior: Benign (typical)
Borderline (rare cases with atypia)
By association: Isolated
Associated with other malignancies (20-30% of cases)
By presentation: Solitary lesion
Multiple lesions.
Epidemiology:
Age distribution: Wide range (17-84 years), median age 55 years
Gender: Slight male predominance
Rarity: <50 cases reported in literature
Association with malignancies: 20-30% of patients have concurrent or subsequent malignancies
Geographic distribution: No specific geographic predilection.
Clinical Features
Presentation:
Splenomegaly most common finding (60-70% of patients)
Asymptomatic in 40-50% of cases (incidental finding)
Left upper quadrant pain when symptomatic
Hypersplenism with cytopenia in some cases
Constitutional symptoms rare unless associated with malignancy.
Symptoms:
Abdominal symptoms: Left upper quadrant discomfort or pain
Early satiety due to splenomegaly
Hematologic symptoms: Fatigue due to anemia
Easy bruising from thrombocytopenia
Systemic symptoms: Generally absent unless complicated
B-symptoms suggest associated malignancy.
Risk Factors:
Immune dysfunction: Possible association with immune system abnormalities
Previous malignancy: Some patients have history of other cancers
Age factor: More common in middle-aged and elderly
No known environmental or genetic predisposing factors identified.
Screening:
Cancer surveillance: Important due to association with other malignancies
Imaging studies: CT or MRI showing splenic lesion
Laboratory studies: Complete blood count, comprehensive metabolic panel
Tissue diagnosis: Required for definitive diagnosis
Multidisciplinary evaluation for associated conditions.
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Gross Description
Appearance:
Multiple small nodules scattered throughout splenic parenchyma
Dark red to purple color similar to blood-filled spaces
Spongy, soft consistency
Size range: Few millimeters to several centimeters
Honeycomb appearance on cut surface due to vascular spaces.
Characteristics:
Multinodular pattern in most cases (80%)
Irregular, anastomosing channels grossly visible
Blood-filled spaces give dark appearance
No true encapsulation
May involve entire spleen or be localized to specific areas.
Size Location:
Diffuse involvement of splenic red pulp in typical cases
Multiple small lesions: 0.5-5 cm each
Rarely solitary large mass
No specific anatomic predilection within spleen
Associated splenomegaly common.
Multifocality:
Multifocal lesions in 80-90% of cases
Bilateral involvement of splenic lobes
Scattered distribution throughout parenchyma
No associated lymphadenopathy
Surrounding splenic tissue may show reactive changes.
Microscopic Description
Histological Features:
Anastomosing vascular channels lined by prominent littoral cells
Papillary projections of lining cells into vascular lumina
Back-to-back arrangement of vascular spaces
Absence of smooth muscle in vessel walls
Red blood cells filling vascular spaces.
Cellular Characteristics:
Littoral cells: Large, plump endothelial-like cells
Vesicular nuclei with small nucleoli
Abundant eosinophilic cytoplasm
Hobnail appearance projecting into lumina
No significant atypia in typical cases
Rare mitotic figures.
Architectural Patterns:
Sinusoidal pattern: Resembles dilated splenic sinusoids
Papillary pattern: Endothelial projections into lumina
Anastomosing pattern: Interconnecting vascular channels
Cavernous areas: Dilated blood-filled spaces
Solid areas: Dense cellular regions.
Grading Criteria:
Benign features: Bland cytology, minimal mitoses, organized architecture
Atypical features: Nuclear pleomorphism, increased mitoses (rare)
No established grading system: Generally considered benign
Borderline cases: May show increased cellularity and atypia.
Immunohistochemistry
Positive Markers:
Endothelial markers: CD31 positive
Factor VIII positive (variable)
Histiocytic markers: CD68 positive (characteristic)
Littoral cell markers: CD21 may be positive
Other markers: Vimentin positive.
Negative Markers:
Smooth muscle markers: SMA negative
Epithelial markers: Cytokeratins negative
Lymphoid markers: CD45 typically negative
Melanoma markers: S-100 usually negative
CD34: May be negative or weakly positive.
Diagnostic Utility:
Dual phenotype confirmation: CD31+ and CD68+ is characteristic
Differential diagnosis: Helps distinguish from other vascular lesions
Littoral cell origin: Unique immunoprofile confirms diagnosis
Excludes other entities: Negative markers rule out other tumors.
Molecular Subtypes:
Classical type: CD31+/CD68+ with typical morphology
Variant patterns: May have different staining intensities
Associated with malignancy: Same immunoprofile but clinical correlation important
Borderline lesions: Similar immunoprofile with increased atypia.
Molecular/Genetic
Genetic Mutations:
Limited molecular data: Few studies on genetic alterations
Chromosomal abnormalities: No consistent patterns identified
Tumor suppressor genes: No consistent alterations reported
Oncogenes: No specific oncogene activation identified.
Molecular Markers:
Angiogenesis markers: VEGF expression variable
Cell cycle markers: Low Ki-67 proliferation index
Apoptosis markers: Normal apoptotic pathways
Immune markers: May express immune-related proteins.
Prognostic Significance:
Generally benign: Excellent prognosis after splenectomy
Association with malignancy: May indicate need for cancer surveillance
Recurrence: Not reported after complete excision
No malignant transformation: Benign behavior maintained.
Therapeutic Targets:
Surgical management: Splenectomy is treatment of choice
Conservative management: Not recommended due to uncertain behavior
Surveillance: For associated malignancies
No specific targeted therapy currently available.
Differential Diagnosis
Similar Entities:
Splenic hemangioma: Pure vascular tumor without CD68 expression
Splenic hamartoma: Different architecture and immunoprofile
Angiosarcoma: Malignant with cytologic atypia
Peliosis: Cystic blood-filled spaces without lining cells
Metastatic disease: Different immunoprofile and clinical context.
Distinguishing Features:
LCA vs hemangioma: CD68+ vs CD68-, different morphology
LCA vs angiosarcoma: Benign vs malignant cytology, different behavior
LCA vs hamartoma: Vascular vs red pulp architecture
Unique immunoprofile: CD31+/CD68+ combination diagnostic.
Diagnostic Challenges:
Rare entity: Limited experience and literature
Sampling issues: Multiple lesions require adequate sampling
Immunohistochemistry essential: Morphology alone may be misleading
Clinical correlation: Association with malignancies important.
Rare Variants:
Solitary LCA: Single large lesion instead of multiple nodules
Atypical LCA: Increased cellularity and atypia
Sclerosed LCA: Fibrotic areas within lesion
Mixed patterns: Combination with other splenic lesions
Pediatric cases: Very rare in children.
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
Splenectomy specimen weighing [X] g with multiple nodular lesions
Gross Description
Multiple dark red nodules measuring [size range] distributed throughout splenic parenchyma
Microscopic Findings
Anastomosing vascular channels lined by prominent littoral cells with [morphologic characteristics]
Immunohistochemical Studies
Lining cells positive for CD31 and CD68, negative for smooth muscle actin
Diagnosis
Splenic littoral cell angioma, multifocal
Biologic Behavior
Benign vascular tumor with excellent prognosis after complete excision
Associated Conditions
Associated with other malignancies in 20-30% of patients
Recommendations
Recommend clinical surveillance for associated malignancies and regular follow-up