What is a leukemic (leukemia) infiltrate in a patient with a history of leukemia?

What is a Leukemic Infiltrate?

A leukemic infiltrate is the pathologic accumulation and invasion of malignant leukemic cells into tissues and organs outside their normal sites of production (bone marrow and blood), representing direct organ involvement by the leukemia itself. 1, 2

Pathophysiology and Mechanism

Leukemic infiltrates occur when abnormal leukemic cells migrate from the bone marrow and peripheral blood to invade various tissues and organs throughout the body. 2 This represents a direct manifestation of the leukemia rather than secondary complications like infection or treatment effects. 2

• In chronic lymphocytic leukemia (CLL), the infiltrate consists of mature monoclonal B lymphocytes that progressively accumulate in blood, bone marrow, spleen, lymph nodes, and can extend to other organs. 3
• In acute leukemias, the infiltrate is composed of immature blast cells (lymphoblasts or myeloblasts) that invade bone marrow and extramedullary sites. 3
• In chronic myeloid leukemia (CML), extramedullary blastic infiltration specifically defines blast crisis when present. 1

Common Sites of Infiltration

Primary Hematopoietic Sites

• Bone marrow: The most common site, where leukemic cells replace normal hematopoietic tissue, often causing fibrosis (particularly in hairy cell leukemia with characteristic "dry tap"). 1
• Spleen and liver: Frequently involved, causing organomegaly in most leukemia types. 1
• Lymph nodes: Common in CLL and some acute leukemias, though less frequent in hairy cell leukemia. 1

Extramedullary Sites

• Skin (leukemia cutis): Occurs in approximately 25% of CLL patients and represents "specific skin lesions" when leukemic cells directly infiltrate the dermis. 4, 5 This can present as papules, nodules, plaques, or ulcerated tumors. 6, 4
• Lungs: Leukemic pulmonary infiltration can occur, distinct from infectious or treatment-related complications. 2
• Gastrointestinal tract: Esophageal infiltration occurs in approximately 7.2% of acute myeloid leukemia cases at autopsy, though rarely diagnosed antemortem. 7
• Central nervous system: More common in lymphoid blast crisis and acute lymphoblastic leukemia. 8
• Heart, pleura, bones, and soft tissues: Can all be affected by direct leukemic involvement. 2

Diagnostic Identification

Morphologic Features

• Bone marrow biopsy shows characteristic infiltration patterns with increased reticulin fibers (especially in hairy cell leukemia). 1
• Peripheral blood smear may show circulating leukemic cells with characteristic morphology. 1
• Tissue biopsies from affected organs demonstrate dense infiltrates of leukemic cells. 6, 7

Immunophenotyping

Distinguishing leukemic infiltrates from reactive lymphoid infiltrates requires immunohistochemistry or flow cytometry:

• CLL infiltrates: CD20+/CD23+/CD5+/CD43+/CD3- phenotype distinguishes them from benign reactive T-cell infiltrates (CD20-/CD23-/CD5+/CD43+/CD3+). 6
• Hairy cell leukemia: Positive for CD19, CD20, CD11c, CD22, CD25, CD103, CD123, and CD200. 1
• Blast crisis: Requires immunophenotyping to determine myeloid versus lymphoid lineage. 9, 8

Molecular Studies

• BRAF V600E mutation is present in most classic hairy cell leukemia cases and can be detected by IHC or molecular studies. 1
• BCR-ABL translocation confirms CML-related infiltrates. 1, 9

Clinical Significance and Prognosis

Prognostic Implications

• Extramedullary blastic infiltration in CML defines blast crisis (≥30% blasts or extramedullary infiltrates), representing transformation to acute leukemia with poor prognosis. 1, 9
• Specific cutaneous infiltration in CLL may indicate transformation to Richter syndrome or unfavorable prognosis, particularly when appearing before CLL diagnosis. 4
• Plasma cell leukemia with extramedullary involvement requires evaluation by imaging (MRI, PET/CT) and justifies immediate therapy upon relapse detection. 1

Important Caveats

• Not all lymphoid infiltrates in leukemia patients are leukemic: Reactive lymphocytes can be recruited to sites of infection or inflammation, and neoplastic cells may be detected without adverse prognostic significance. 5 For example, CLL cells may accumulate at sites of herpes simplex infection as part of a physiologic immune response. 5
• Dense peritumoral infiltrates around non-melanoma skin cancers in CLL patients represent leukemic cells but may obscure tumor margins and complicate assessment of perineural spread. 6
• High initial leukocyte count is significantly associated with increased risk of organ infiltration (e.g., esophageal involvement in acute myeloid leukemia). 7

Distinction from Other Findings

Leukemic infiltrates must be distinguished from:

• Infectious complications: The most common cause of organ dysfunction in leukemia patients. 2
• Treatment-related toxicity: Chemotherapy and radiation effects on organs. 2
• Secondary malignancies: Patients with CLL have 8 times higher risk of skin cancer than the general population. 4
• Reactive lymphoid hyperplasia: Benign immune responses that can mimic leukemic infiltration. 5