Definition/General
Introduction:
Splenic metastasis refers to secondary tumor deposits within the spleen from primary malignancies elsewhere in the body
Although historically considered uncommon, modern imaging and autopsy studies reveal splenic metastases in 2.3-7.1% of patients with disseminated cancer
The spleen was traditionally thought to be resistant to metastasis due to its unique vascular anatomy and immunologic functions.
Origin:
Metastatic deposits reach the spleen through hematogenous spread, direct extension from adjacent organs, or lymphatic dissemination
The spleen's dual blood supply from splenic artery and extensive sinusoidal network facilitates tumor cell seeding
Immune surveillance mechanisms may initially resist metastatic colonization
However, advanced malignancies can overcome these protective mechanisms.
Classification:
By route of spread: Hematogenous (most common)
Direct extension from adjacent organs
Lymphatic dissemination
By pattern: Solitary lesions
Multiple discrete nodules
Diffuse infiltration
By primary site: Breast carcinoma (most common)
Lung carcinoma
Melanoma
Colorectal carcinoma
Ovarian carcinoma.
Epidemiology:
Splenic metastases found in 2.3-7.1% of cancer patients at autopsy
Breast carcinoma accounts for 25-30% of cases
Lung cancer represents 20-25% of cases
More common in advanced stage disease
Synchronous presentation in 60-70% of cases
Metachronous presentation in 30-40% of cases.
Clinical Features
Presentation:
Asymptomatic in majority of patients (60-70%)
Splenomegaly in 50-60% of cases
Left upper quadrant pain and discomfort
Early satiety due to gastric compression
Constitutional symptoms related to primary malignancy
Hypersplenism with cytopenia in advanced cases.
Symptoms:
Abdominal symptoms: Left-sided abdominal pain
Abdominal fullness and distension
Early satiety and nausea
Systemic symptoms: Fatigue and weakness
Weight loss and anorexia
Complications: Spontaneous splenic rupture (rare)
Bleeding due to thrombocytopenia
Recurrent infections.
Risk Factors:
Primary tumor characteristics: Advanced stage at diagnosis
High-grade histology
Extensive metastatic disease
Specific primary sites: Breast carcinoma (especially invasive lobular)
Lung adenocarcinoma
Melanoma
Ovarian carcinoma
Patient factors: Immunocompromised state
Multiple prior treatments.
Screening:
Routine imaging in advanced cancer patients
CT chest, abdomen, pelvis for staging workup
PET-CT for detecting occult metastases
Follow-up imaging in patients with known metastatic disease
Clinical suspicion in patients with unexplained splenomegaly and known malignancy.
Master Splenic Metastasis Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Variable spleen size from normal to massively enlarged (up to 2000g)
Multiple discrete nodules ranging from few millimeters to several centimeters
Gray-white to tan-colored lesions with well-demarcated borders
Areas of hemorrhage and necrosis may be present
Cut surface shows fish-flesh appearance in some cases.
Characteristics:
Firm to hard consistency of metastatic deposits
Capsular involvement may cause surface irregularities
Hilar involvement with possible extension to adjacent structures
Cystic degeneration may occur in older lesions
Calcification rare except in specific tumor types (mucinous adenocarcinoma).
Size Location:
Size variation: From microscopic foci to masses >10 cm
Distribution patterns: Random throughout parenchyma
Subcapsular predilection in some cases
Multiple lesions more common than solitary masses
Red pulp involvement more frequent than white pulp.
Multifocality:
Multifocal involvement in 80-90% of cases
Bilateral involvement of splenic lobes
Associated findings: Hepatic metastases (70-80%)
Peritoneal carcinomatosis
Lymph node involvement
Direct extension from pancreatic tail, stomach, or left kidney in some cases.
Microscopic Description
Histological Features:
Metastatic deposits show histologic features of primary tumor
Preservation of splenic architecture between tumor deposits
Sinusoidal involvement common with carcinomatous pattern
Desmoplastic reaction around tumor deposits variable
Inflammatory infiltrate may be present at periphery of lesions.
Cellular Characteristics:
Morphology reflects primary site: Glandular pattern in adenocarcinomas
Solid sheets in poorly differentiated carcinomas
Nuclear features: Pleomorphism consistent with grade
Prominent nucleoli in many cases
Cytoplasmic characteristics: Abundant in breast carcinoma
Mucin production in mucinous adenocarcinomas.
Architectural Patterns:
Adenocarcinoma pattern: Gland formation with luminal spaces
Solid nests and cords
Squamous carcinoma: Keratinization and intercellular bridges
Melanoma pattern: Solid sheets with melanin pigment
Neuroendocrine pattern: Trabecular and nested architecture
Sarcomatous pattern: Spindle cell morphology.
Grading Criteria:
Histologic grade usually matches primary tumor
Well-differentiated: Preserved architectural features
Minimal nuclear pleomorphism
Moderately differentiated: Some architectural distortion
Moderate pleomorphism
Poorly differentiated: Loss of differentiation features
Marked nuclear pleomorphism and mitotic activity.
Immunohistochemistry
Positive Markers:
Site-specific markers: TTF-1 for lung primary
ER/PR for breast primary
CDX-2 for colorectal primary
PAX-8 for ovarian/renal primary
Melanoma markers: S-100, Melan-A, HMB-45
Carcinoma markers: Pan-cytokeratin (AE1/AE3)
EMA
Neuroendocrine markers: Chromogranin, synaptophysin.
Negative Markers:
Splenic markers: CD68 (red pulp macrophages)
CD21 (follicular dendritic cells)
Lymphoid markers: CD20, CD3 (unless lymphoma)
Site-specific negatives help exclude other primaries
Vimentin usually negative in carcinomas (positive in sarcomas).
Diagnostic Utility:
Primary site identification crucial for staging and treatment
Tissue-specific markers help narrow differential diagnosis
Multiple marker panels often required for definitive diagnosis
Morphologic correlation essential for interpretation
Clinical history guides marker selection.
Molecular Subtypes:
Breast carcinoma subtypes: Luminal (ER+/PR+), HER2-enriched (HER2+), Triple-negative
Lung adenocarcinoma: EGFR, ALK, ROS1 status
Colorectal carcinoma: Microsatellite instability status
Melanoma: BRAF, NRAS mutation status
Molecular profiling guides targeted therapy.
Molecular/Genetic
Genetic Mutations:
Primary site-specific mutations: KRAS in colorectal carcinoma
EGFR in lung adenocarcinoma
BRAF in melanoma
PIK3CA in breast carcinoma
TP53 mutations common across multiple tumor types
Microsatellite instability in some colorectal and endometrial carcinomas.
Molecular Markers:
Gene expression profiles help identify primary site in carcinoma of unknown primary
Mutation-specific therapies: EGFR inhibitors for EGFR-mutant lung cancer
BRAF inhibitors for BRAF-mutant melanoma
Immunotherapy markers: PD-L1 expression
Microsatellite instability status
Tumor mutational burden.
Prognostic Significance:
Molecular subtype affects prognosis and treatment response
Mutation burden correlates with immunotherapy response
Driver mutations predict targeted therapy efficacy
Resistance mutations may develop with treatment
Liquid biopsies can monitor disease progression.
Therapeutic Targets:
Targeted therapy based on molecular profile of primary tumor
Immunotherapy: PD-1/PD-L1 inhibitors for MSI-high tumors
Precision medicine approaches for rare mutations
Combination therapies for improved efficacy
Clinical trials for novel targeted agents.
Differential Diagnosis
Similar Entities:
Primary splenic neoplasms: Angiosarcoma, littoral cell angioma, lymphoma
Reactive conditions: Inflammatory pseudotumor, granulomatous disease
Infectious lesions: Abscess, fungal infections, tuberculosis
Benign tumors: Hemangioma, hamartoma, inflammatory myofibroblastic tumor.
Distinguishing Features:
Metastasis vs primary: Clinical history of known malignancy
Multiple lesions favor metastasis
Immunohistochemical profile
Carcinoma vs lymphoma: Cytokeratin positivity in carcinoma
CD45 positivity in lymphoma
Adenocarcinoma vs reactive: Cytologic atypia and architectural abnormalities.
Diagnostic Challenges:
Unknown primary site: Requires extensive immunohistochemical workup
Poorly differentiated tumors may lose site-specific features
Mixed patterns in metastatic deposits
Small biopsies may limit diagnostic accuracy
Concurrent primary splenic tumors rare but possible.
Rare Variants:
Cystic metastases: From ovarian or mucinous primaries
Hemorrhagic metastases: Melanoma, renal cell carcinoma, choriocarcinoma
Calcified metastases: Mucinous adenocarcinomas, treated lesions
Necrotic metastases: Rapidly growing tumors
Pseudomyxoma peritonei with splenic involvement.
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
Spleen, [procedure type], weighing [X] g, with clinical history of [primary malignancy]
Gross Description
The spleen contains [number] discrete nodules measuring [size range], with [color and consistency]
Microscopic Findings
Sections show metastatic [tumor type] with [architectural pattern] and [cellular features]
Immunohistochemical Studies
The tumor cells are positive for [site-specific markers] and negative for [exclusion markers]
Molecular Studies
Molecular analysis shows [mutations/alterations] consistent with [primary site]
Diagnosis
Metastatic [tumor type] involving spleen, consistent with [primary site] origin
Staging Information
Splenic metastasis represents [stage designation] disease with [extent of involvement]
Recommendations
Recommend [molecular testing/staging studies] and correlation with [primary tumor characteristics]