Definition/General
Introduction:
Splenic inflammatory pseudotumor (IPT) is a rare benign lesion characterized by chronic inflammatory infiltrate with fibroblastic and myofibroblastic proliferation
Also known as inflammatory myofibroblastic tumor (IMT) when showing myofibroblastic differentiation
It represents a reactive process rather than a true neoplasm
IPT can mimic malignancy clinically and radiologically, making histopathologic diagnosis crucial.
Origin:
Represents an exuberant inflammatory response to unknown stimulus
May develop following infection, trauma, or autoimmune process
Chronic inflammation leads to fibroblastic proliferation and tissue remodeling
Myofibroblastic differentiation occurs in some cases
The exact trigger often remains unidentified.
Classification:
Histologic patterns: Plasma cell-rich type
Lymphocyte-rich type
Myofibroblastic type (IMT)
ALK status: ALK-positive IMT
ALK-negative IMT
By location: Localized mass
Multifocal involvement
By behavior: Benign reactive
Locally aggressive (rare).
Epidemiology:
Age distribution: Can occur at any age, slight predilection for young adults
Gender: Equal male-female distribution
Rarity: <100 cases reported in literature
Geographic variation: No specific geographic predilection
Etiology: Most cases have unknown precipitating factors.
Clinical Features
Presentation:
Left upper quadrant pain most common symptom (70-80%)
Fever in 40-50% of patients
Splenomegaly in symptomatic cases
Constitutional symptoms: Weight loss, fatigue, malaise
Laboratory abnormalities: Elevated ESR, CRP, anemia.
Symptoms:
Abdominal symptoms: Left upper quadrant pain and fullness
Early satiety if mass effect present
Systemic symptoms: Low-grade fever, night sweats
Weight loss and decreased appetite
Inflammatory symptoms: Fatigue and malaise
Acute presentation possible if rapid growth.
Risk Factors:
Infectious triggers: Previous bacterial, viral, or parasitic infections
Autoimmune conditions: Association with inflammatory bowel disease, autoimmune hepatitis
Trauma history: Blunt abdominal trauma in some cases
Immunosuppression: May predispose to development.
Screening:
Clinical suspicion: Inflammatory symptoms with splenic mass
Laboratory studies: Elevated inflammatory markers (ESR, CRP)
Complete blood count, comprehensive metabolic panel
Imaging studies: CT or MRI showing heterogeneous splenic mass
Tissue diagnosis: Required to exclude malignancy.
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Gross Description
Appearance:
Well-circumscribed mass with firm, white-tan cut surface
Whorled appearance due to fibrous tissue
Areas of hemorrhage and necrosis may be present
Variable size: From few centimeters to large masses
Gritty consistency due to calcification in chronic cases.
Characteristics:
Solid lesion without cystic areas in typical cases
Fibrous consistency ranging from soft to rock-hard
Gray-white color with possible yellow areas (necrosis)
May show calcification in longstanding cases
Irregular borders in some cases.
Size Location:
Size range: 2-20 cm (average 5-8 cm)
Location: Any part of spleen, no specific predilection
Usually solitary but multiple lesions possible
Well-demarcated from surrounding normal spleen
Capsular involvement rare.
Multifocality:
Solitary lesions in majority (>90%) of cases
Multifocal involvement rare but reported
No associated lymphadenopathy typically
Surrounding splenic tissue usually normal
Adhesions to adjacent organs possible in large lesions.
Microscopic Description
Histological Features:
Mixed inflammatory infiltrate with lymphocytes, plasma cells, and eosinophils
Fibroblastic proliferation with spindle cell areas
Myofibroblastic differentiation in IMT cases
Vascular proliferation with endothelial cell prominence
Foamy macrophages and giant cells may be present.
Cellular Characteristics:
Spindle cells: Bland fibroblasts and myofibroblasts without significant atypia
Inflammatory cells: Mixture of chronic inflammatory elements
Plasma cells: Often prominent, may be polyclonal
Lymphocytes: T and B cells in variable proportions
Eosinophils: May be numerous.
Architectural Patterns:
Myxoid areas: Loose myxoid stroma in some regions
Fibrous areas: Dense collagenous tissue
Fascicular pattern: Spindle cells in intersecting fascicles
Inflammatory nodules: Discrete collections of inflammatory cells
Vascular pattern: Prominent capillary proliferation.
Grading Criteria:
Benign features: Bland spindle cells, mixed inflammation, low mitotic rate
Atypical features: Increased cellularity, mild atypia (still benign)
No malignant transformation: Does not progress to sarcoma
Mitotic activity: Usually low (<5 per 10 HPF).
Immunohistochemistry
Positive Markers:
Myofibroblastic markers: Smooth muscle actin (SMA) in myofibroblasts
ALK protein: Positive in 50-60% of IMT cases
Vimentin: Positive in spindle cells
Inflammatory markers: CD68 in macrophages, CD3/CD20 in lymphocytes.
Negative Markers:
Epithelial markers: Cytokeratins negative in spindle cells
Melanoma markers: S-100, Melan-A negative
Sarcoma markers: Specific sarcoma markers negative
Lymphoma markers: Spindle cells negative for lymphoid markers.
Diagnostic Utility:
ALK status determination: Important for classification and potential targeted therapy
Myofibroblastic confirmation: SMA positivity supports myofibroblastic differentiation
Exclusion of malignancy: Negative tumor markers
Inflammatory nature: Mixed inflammatory cell population.
Molecular Subtypes:
ALK-positive IMT: Better defined entity with potential for ALK inhibitor therapy
ALK-negative cases: More heterogeneous group with variable behavior
Plasma cell-rich variant: Prominent plasma cell infiltrate
Myxoid variant: Prominent myxoid stroma.
Molecular/Genetic
Genetic Mutations:
ALK rearrangements: Various fusion partners including TPM3-ALK, TPM4-ALK
ROS1 rearrangements: In some ALK-negative cases
PDGFRA mutations: Rare cases with PDGFRA alterations
Other fusions: Various novel fusions being identified.
Molecular Markers:
ALK protein expression: Due to chromosomal rearrangements
Inflammatory cytokines: IL-6, TNF-α, various interleukins
Growth factors: PDGF, FGF expression
Angiogenesis markers: VEGF in vascular areas.
Prognostic Significance:
Generally benign behavior: Excellent prognosis after complete excision
ALK status: May influence treatment options
Recurrence: Rare after complete excision
Malignant transformation: Not reported in splenic cases.
Therapeutic Targets:
ALK inhibitors: Crizotinib for ALK-positive cases (if needed)
Anti-inflammatory therapy: Corticosteroids in some cases
Surgical excision: Primary treatment approach
Conservative management: Possible for small asymptomatic lesions.
Differential Diagnosis
Similar Entities:
Splenic lymphoma: May have inflammatory component but shows lymphoid atypia
Splenic sarcoma: Malignant spindle cell tumor with significant atypia
Splenic metastases: From sarcomatoid carcinomas or sarcomas
Infectious conditions: Chronic abscess, granulomatous inflammation
Autoimmune conditions: Autoimmune splenitis.
Distinguishing Features:
IPT vs lymphoma: Mixed inflammation vs monomorphic lymphoid population
ALK+ vs lymphoid markers
IPT vs sarcoma: Bland vs atypical spindle cells
Mixed inflammation vs pure sarcomatous pattern
Clinical correlation: Inflammatory symptoms vs constitutional symptoms.
Diagnostic Challenges:
Sampling issues: May require large tissue samples for accurate diagnosis
Inflammatory vs neoplastic: Distinction may be difficult in some cases
ALK testing: Requires specific immunohistochemistry or molecular testing
Clinical correlation: Important for distinguishing from reactive conditions.
Rare Variants:
Calcifying fibrous tumor: Variant with prominent calcification
Nodular fasciitis-like: Resembles nodular fasciitis pattern
Plasma cell granuloma: Predominantly plasma cell infiltrate
Xanthogranulomatous: Prominent foamy macrophages
EBV-associated: Related to Epstein-Barr virus infection.
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
[Biopsy/splenectomy] specimen with clinical history of [inflammatory symptoms] and splenic mass
Gross Description
Well-circumscribed mass measuring [dimensions] with [firm consistency] and [whorled cut surface]
Microscopic Findings
Mixed inflammatory infiltrate with [spindle cell proliferation] and [myofibroblastic differentiation]
Immunohistochemical Studies
Spindle cells positive for [SMA/vimentin]. ALK: [positive/negative]. Inflammatory markers appropriate
ALK Status
ALK immunostain: [positive/negative] - [implications for classification]
Diagnosis
Splenic inflammatory [pseudotumor/myofibroblastic tumor], ALK-[positive/negative]
Biologic Behavior
Benign reactive lesion with excellent prognosis after complete excision
Recommendations
Complete excision curative. [ALK inhibitor consideration if ALK-positive and residual disease]