Hematopoietic Neoplasms of the Liver - MD Pathology

Classification

1. Primary hepatic lymphoma (PHL)
2. Secondary (systemic) involvement - lymphoma, leukemia, myeloma
3. Myeloid sarcoma (chloroma)
4. Post-transplant lymphoproliferative disorder (PTLD)
5. Miscellaneous - Castleman disease, hemophagocytic lymphohistiocytosis (HLH), plasmacytoma

1. Primary Hepatic Lymphoma (PHL)

• Very rare: ~0.016% of all NHL; ~0.4% of extranodal NHL
• Male predominance; age 50-60 years

• Most common type: Diffuse Large B-Cell Lymphoma (DLBCL) (~50-70%)
• Others: Follicular lymphoma, MALT lymphoma (marginal zone), Burkitt lymphoma, T-cell lymphoma (rare)

• Chronic hepatitis B or C infection
• EBV infection / immunosuppression
• HIV/AIDS
• Autoimmune hepatitis
• NASH / cirrhosis (MALT lymphoma)
• Chronic inflammation promoting lymphomagenesis

• Hepatomegaly, RUQ pain, fever, weight loss (B symptoms)
• Elevated LFTs, LDH
• May mimic HCC clinically and radiologically

• Gross: single or multiple nodules; rarely diffuse infiltration
• Micro: sheets of atypical lymphoid cells effacing hepatic architecture
• Sinusoidal pattern of infiltration is characteristic
• IHC: CD20+, CD79a+ (B-cell markers); bcl-2, bcl-6, MUM-1 in DLBCL

2. Secondary Hepatic Involvement

By Lymphoma

• Far more common than primary PHL
• Hodgkin lymphoma: liver involved in 10-15% at diagnosis; portal tract infiltration with Reed-Sternberg cells
• NHL (Non-Hodgkin lymphoma): 50-60% of advanced NHL cases; DLBCL, follicular, mantle cell, Burkitt
• Pattern: Portal tract infiltration (most common), sinusoidal infiltration, discrete nodules

By Leukemia

• CLL/SLL: Portal and sinusoidal infiltration by small lymphocytes; most common leukemia to involve liver
• AML: Sinusoidal infiltration by blasts; may cause biliary obstruction via periductal infiltration
• CML: Hepatomegaly with granulocytic precursor infiltration (sinusoidal)
• ALL: Rare; portal + sinusoidal infiltration

By Multiple Myeloma / Plasmacytoma

• Hepatic plasmacytomas; plasma cell infiltration in sinusoids/portal tracts
• Associated with hepatomegaly and elevated alkaline phosphatase
• Skeletal lytic lesions often present on imaging

3. Myeloid Sarcoma (Granulocytic Sarcoma / Chloroma)

• Extramedullary proliferation of immature myeloid cells forming a discrete tumor mass
• Associated with: AML (most common, 3-5%), CML, MDS, polycythemia vera, essential thrombocythemia
• May occur during remission or relapse of underlying disease (up to 20% in remission)
• Green tinge on gross due to myeloperoxidase (hence "chloroma")
• Micro: sheets of immature myeloid cells (myeloblasts, promyelocytes); positive for myeloperoxidase, CD43, CD117, lysozyme
• Hepatic lesions are more heterogeneously enhancing and less well-defined than lymphoma
• Key exam point: AML + extramedullary mass = myeloid sarcoma; treat as AML even in the absence of bone marrow disease

4. Post-Transplant Lymphoproliferative Disorder (PTLD)

• Occurs in recipients of solid organ or hematopoietic stem cell transplants
• Pathogenesis: EBV-driven proliferation in setting of iatrogenic immunosuppression
• WHO classification (4 types):
  1. Early hyperplastic lesions (plasmacytic hyperplasia)
  2. Polymorphic PTLD
  3. Monomorphic PTLD (most resemble specific lymphoma types, often DLBCL)
  4. Classic Hodgkin lymphoma-type PTLD
• Liver involvement is common in monomorphic PTLD
• Clinical features that suggest hematologic malignancy in post-transplant liver lesions: young patient, no prior malignancy, fever, night sweats, abnormal bone marrow

5. Hemophagocytic Lymphohistiocytosis (HLH)

• Hyperactivation of macrophages / histiocytes, often triggered by hematologic malignancies (NK/T-cell lymphoma most commonly)
• Liver shows hemophagocytosis - macrophages engulfing RBCs, WBCs, platelets in sinusoids
• Key feature: hepatomegaly with severe transaminitis, coagulopathy, hyperferritinemia
• Fatal if untreated; treat underlying trigger

Key Exam Points (Summary Table)

Clinical Clues Favoring Hematologic Malignancy (vs. Epithelial Liver Tumor)

• Age <40 years
• No known primary cancer
• Fever, night sweats, weight loss (B symptoms)
• Hepatosplenomegaly with widespread lymphadenopathy (above + below diaphragm)
• Vascular encasement without thrombosis
• Infiltrating hilar mass without biliary obstruction
• Abnormal bone marrow biopsy