Primary Splenic Non-Hodgkin's Lymphoma: Definition and Pathophysiology
Definition
Primary splenic lymphoma (PSL) is a rare entity defined as lymphomatous involvement limited to the spleen and splenic hilum only, without evidence of nodal or other extrasplenic disease at diagnosis, comprising less than 1-2% of all non-Hodgkin's lymphomas. 1, 2, 3, 4
Diagnostic Criteria
- Lymphoma must originate within the spleen with involvement restricted to the spleen and splenic hilum (Stage 1-2 disease) 2, 4
- No biopsy-proven evidence of extrasplenic disease, including liver or lymph nodes, at time of diagnosis 2
- The definition remains somewhat ambiguous in the literature, with some experts allowing for later metastatic spread while others requiring strict splenic confinement 3, 4
Histologic Subtypes
The most common PSL variants include:
- Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) 5
- Splenic marginal zone lymphoma (SMZL) 5
- Splenic red pulp small B-cell lymphoma 5
- Splenic hairy cell leukemia variant 5
- Most PSLs are of B-cell origin, showing low or intermediate-grade histology on pathologic analysis 3
Pathophysiology
Cellular Origin and Development
- PSL develops from malignant transformation of B-lymphocytes within the splenic white pulp or red pulp compartments 6
- The spleen, being a major lymphoid organ, provides a microenvironment conducive to lymphoproliferation, though the exact mechanisms triggering primary splenic lymphomagenesis remain poorly understood 5
- Unlike secondary splenic involvement in disseminated NHL (which is common), PSL represents de novo malignant transformation within splenic tissue 4
Clinical Manifestations
The pathophysiology manifests through:
- Progressive splenomegaly causing mechanical symptoms including left upper quadrant pain, early satiety, and abdominal distension 2, 3
- Nonspecific systemic B-symptoms including low-grade fevers, night sweats, and weight loss 3
- Cytopenias resulting from hypersplenism and bone marrow involvement (when present) 1
- Rare complications include hemophagocytic lymphohistiocytosis (HLH) with fever, cytopenia, hepatosplenomegaly, hyperferritinemia, and phagocytosis of hematopoietic cells 1
- Spontaneous splenic rupture can occur, particularly after chemotherapy initiation 1
Epidemiologic Context
- Non-Hodgkin's lymphoma overall accounts for approximately 4% of all new cancer cases, with PSL representing a small fraction of this burden 7
- The rarity of PSL (less than 1-2% of NHL cases) makes standardized diagnostic and treatment approaches challenging 1, 2, 3
Diagnostic Challenges
- Fine-needle aspirate and core needle biopsy of the spleen are not routinely offered at most medical centers, making preoperative diagnosis difficult 5
- Splenectomy often serves as both diagnostic and therapeutic intervention 2, 5
- Clinical presentations can be nonspecific, sometimes mimicking other conditions such as nephrolithiasis 3