What are the clinical features of primary splenic non-Hodgkin's lymphoma?

Clinical Features of Primary Splenic Non-Hodgkin's Lymphoma

Primary splenic non-Hodgkin's lymphoma typically presents with massive splenomegaly accompanied by nonspecific systemic symptoms, and most commonly represents splenic marginal zone lymphoma (SMZL) in the B-cell lineage. 1

Key Presenting Features

Splenic Manifestations

• Splenomegaly is the hallmark finding, often massive in size, and may be the sole presenting feature or discovered incidentally on imaging 2, 3, 4
• Symptomatic splenomegaly causing left upper quadrant or flank pain occurs frequently 2, 3, 4
• The spleen typically shows either a solitary large mass (>5 cm), multifocal masses of varying sizes (1-10 cm), or diffuse enlargement without discrete masses on imaging 4

Hematologic Abnormalities

• Peripheral lymphocytosis is common, with some patients diagnosed incidentally from routine blood work showing elevated lymphocyte counts 1
• Cytopenias, particularly thrombocytopenia and anemia, occur in advanced cases due to splenic sequestration and bone marrow involvement 1, 3
• Bone marrow infiltration is frequently present, occurring in conjunction with splenic disease 1

Systemic Symptoms

• Nonspecific B symptoms including low-grade fevers, drenching night sweats, and unexplained weight loss (>10% over 6 months) are characteristic 1, 2
• Fatigue and generalized weakness are common complaints 5
• These systemic symptoms are less prominent than in nodal lymphomas but should prompt investigation 2

Anatomic Distribution Patterns

Sites of Involvement

• The spleen and splenic hilar lymph nodes are the primary sites of disease by definition 1, 6
• Blood involvement is frequent, distinguishing SMZL from other marginal zone lymphomas 1
• Bone marrow is commonly infiltrated at presentation 1
• Distant lymph node enlargement may occur in approximately 20% of cases, though this challenges the "primary" designation 1

Imaging Characteristics

• On ultrasound, lesions appear hypoechoic in 90% of cases 4
• On contrast-enhanced CT, masses are hypodense relative to normal splenic parenchyma in the majority of cases 4
• Four main patterns exist: solitary large mass without necrosis (most common), solitary mass with central necrosis, multifocal masses, or miliary studding 4

Autoimmune and Immunologic Features

Approximately 20% of patients develop autoimmune manifestations, which is a distinctive feature of splenic marginal zone lymphoma specifically 1:

• Autoimmune hemolytic anemia (AIHA) 1
• Immune thrombocytopenia 1
• Cold agglutinin disease 1
• Circulating anticoagulants or acquired von Willebrand disease 1
• Acquired C1-esterase inhibitor deficiency causing angioedema 1

Histologic Subtypes

Most Common Types

• Low-grade B-cell lymphomas predominate, particularly splenic marginal zone lymphoma 2, 7
• Intermediate-grade histologies occur less frequently 7
• High-grade lymphomas like diffuse large B-cell lymphoma (DLBCL) are rare but aggressive presentations 3

Prognostic Implications

• The histologic grade does not consistently correlate with prognosis in truly primary splenic disease (limited to spleen and splenic hilum) 7, 6
• When strictly defined and pathologically staged, primary splenic lymphoma has a favorable prognosis with median survival exceeding 7 years 7

Diagnostic Considerations

Clinical Pitfalls

• The presentation may mimic other conditions such as nephrolithiasis when flank pain is prominent, leading to diagnostic delays 2
• Incidental discovery during imaging for unrelated complaints is not uncommon 4
• The nonspecific nature of systemic symptoms often results in delayed diagnosis 2

Staging Requirements

• CT scanning of chest, abdomen, and pelvis is mandatory to exclude extrasplenic disease 1
• PET-CT should be considered if high-grade transformation is suspected 1
• Abdominal sonography may provide additional information for detecting splenic focal lesions beyond CT 1
• Bone marrow biopsy is not routinely required if PET-CT is performed, given its high sensitivity for marrow involvement 1

Important Clinical Caveats

• True primary splenic lymphoma (involving only spleen and splenic hilum) comprises less than 1-2% of all non-Hodgkin's lymphomas, making it a rare diagnosis 2, 6
• The definition of "primary" splenic lymphoma varies in the literature—strict definitions require disease limited to spleen and splenic hilum only, while broader definitions allow for later spread 2, 6
• Splenectomy may be required for definitive diagnosis when imaging-guided biopsy is not feasible or diagnostic 4
• The favorable prognosis reported in some series applies specifically to pathologically staged, truly localized disease, not cases with occult dissemination 7, 6