What are the histopathological differences between benign and malignant retroperitoneal fibrosis (RPF)?

Histopathological Differentiation of Benign vs Malignant Retroperitoneal Fibrosis

Biopsy is mandatory to definitively distinguish malignant from benign retroperitoneal fibrosis, as imaging alone cannot reliably differentiate between these entities. 1

Key Histopathological Features

Benign (Idiopathic) Retroperitoneal Fibrosis

• Fibroblast proliferation with excessive collagen deposition without malignant cellular features 2
• Fibroinflammatory tissue characterized by aberrant proliferation surrounding retroperitoneal vessels 3
• Immune-mediated inflammatory infiltrate consistent with autoimmune pathogenesis 4
• Absence of malignant cells on tissue examination 5
• May show IgG4-positive plasma cell infiltration in cases associated with IgG4-related disease 4

Malignant Retroperitoneal Fibrosis

• Presence of malignant cells within the fibrotic tissue, representing either:
  • Primary retroperitoneal sarcoma (liposarcoma, leiomyosarcoma) 1, 6
  • Metastatic carcinoma with desmoplastic reaction 5
  • Lymphoma (requires exclusion via CD45/LCA staining and flow cytometry) 1, 7
  • Germ cell tumor components 7

Critical Diagnostic Algorithm

Step 1: Obtain Tissue Diagnosis

• Image-guided core needle biopsy is preferred over open surgical biopsy to establish diagnosis and histologic subtype 1
• Never proceed with major surgical resection before establishing diagnosis, as this prevents inappropriate resection of lymphoma, germ cell tumors, or benign inflammatory conditions 1

Step 2: Immunohistochemical Panel

• CD45 (LCA) staining: Positivity suggests lymphoma but can be seen in certain germ cell tumor components 7
• Pan-cytokeratin: Negativity argues against carcinoma but does not exclude germ cell tumors 7
• IgG4 immunostaining: Elevated IgG4-positive plasma cells suggest IgG4-related disease 4
• If lymphoma cannot be excluded: Core needle biopsy may be insufficient; consider repeat biopsy with flow cytometry and additional immunohistochemical staining 7

Step 3: Distinguish Histologic Subtypes if Malignant

• Liposarcoma: Requires extended resection including adjacent viscera due to poorly defined margins 1, 6
• Leiomyosarcoma: Complete tumor resection with involved organs only, as these have more clearly defined borders 1, 6
• Lymphoma or germ cell tumors: Require completely different chemotherapy-based treatment approaches rather than surgical resection 1, 7

Common Diagnostic Pitfalls

Imaging Cannot Replace Histology

• Imaging features may suggest benign vs malignant RPF but histopathologic examination is needed for definitive diagnosis 3
• Malignant RPF accounts for up to 10% of cases and has dismal prognosis compared to excellent prognosis for benign forms 8, 3

Secondary Causes Mimic Idiopathic Disease

• Malignancy-related RPF may show typical findings of idiopathic RPF on biopsy, representing desmoplastic reaction rather than direct tumor infiltration 5
• MRPF may appear 1-15 years after cancer diagnosis or simultaneously with cancer presentation 5
• Consider drug-related causes (methysergide), infections, radiotherapy, and Erdheim-Chester disease in differential 8, 4

Inadequate Sampling

• Core needle biopsy may be insufficient if complex differential diagnosis remains after initial pathology review 7
• Surgical biopsy remains the only way to definitively establish diagnosis in equivocal cases 8

Clinical Context for Interpretation

Benign RPF typically demonstrates:

• Perivascular distribution supporting immune-mediated response to atherosclerosis 8
• May be part of systemic fibrosing disease or multifocal fibro-inflammatory disorder 8, 4
• Good prognosis if promptly diagnosed and treated 8, 3

Malignant RPF demonstrates:

• Malignant cellular infiltration within fibrotic tissue 5
• Poor prognosis requiring aggressive surgical resection with negative margins 1
• May require neoadjuvant radiotherapy (45-50 Gy) to improve resectability 1