Can Cancer Cause Granulocytosis?
Yes, cancer can definitively cause granulocytosis through paraneoplastic production of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) by tumor cells, and this phenomenon is well-documented across multiple solid tumor types and hematologic malignancies.
Mechanisms of Cancer-Associated Granulocytosis
Paraneoplastic G-CSF/GM-CSF Production
Solid tumors can autonomously produce colony-stimulating factors that directly stimulate granulocyte proliferation, leading to marked peripheral blood granulocytosis with mature neutrophils 1, 2, 3.
Tumor extracts from malignancies associated with granulocytosis demonstrate colony-stimulating activity at both protein and mRNA levels, confirming autocrine production by neoplastic cells 1, 2, 3.
The elevation of granulocyte count typically parallels tumor burden, with counts decreasing temporarily after tumor-directed therapy (radiation or surgery) and rising again with disease progression 1, 3.
Specific Cancer Types Associated with Granulocytosis
Large cell lung cancer has been documented to produce GM-CSF, causing leukocytosis up to 48,300/μL with associated eosinophilia 1.
Glioblastoma multiforme can produce very high levels of G-CSF, causing excessive granulocytosis that may mimic brain abscess clinically 2.
Non-small cell lung cancer with G-CSF production demonstrates extreme neutrophilia (150,000-240,000 WBC count) and correlates with significantly shorter survival 4.
Various malignancies from different anatomic sites have demonstrated this phenomenon, characterized by marked granulocytosis with mature neutrophils, nonspecific inflammatory signs, and rapid progressive disease course 3.
Hematologic Malignancies and Granulocytosis
Chronic Myeloid Leukemia (CML)
CML presents with pathognomonic leukocytosis featuring basophilia and immature granulocytes (metamyelocytes, myelocytes, promyelocytes) with few myeloblasts, often accompanied by thrombocytosis 5, 6.
The differential leukocyte count in CML is highly specific and diagnostic, with marked granulocytic leukocytosis being a defining hematologic parameter 6.
Bone marrow shows increased cellularity due to granulocytic proliferation with myelocytes and segmented forms predominating 5.
Acute Myeloid Leukemia (AML)
- AML typically presents with myeloblasts, monoblasts, or megakaryoblasts in peripheral blood, though this is usually accompanied by anemia and thrombocytopenia rather than isolated granulocytosis 5.
Myeloproliferative Neoplasms with Monocytosis
The constellation of thrombocytosis, anemia, lymphocytosis, and monocytosis suggests chronic myelomonocytic leukemia (CMML) or an MPN with monocytosis, requiring immediate hematology consultation 7.
Key features include absolute monocyte count ≥1×10⁹/L, dysplasia on peripheral smear, splenomegaly, and constitutional symptoms 7.
Clinical Characteristics and Diagnostic Approach
Distinguishing Features
Paraneoplastic granulocytosis shows mature neutrophils without significant left shift, distinguishing it from leukemia where immature forms predominate 3.
Postmortem examination in paraneoplastic cases reveals no extensive bone marrow metastases or significant suppuration, with bone marrow showing granulocytic hyperplasia of varying degrees 3.
Serum G-CSF levels are markedly elevated (e.g., 112 pg/mL versus normal <2.0 pg/mL for GM-CSF) and can be measured by ELISA 1.
Prognostic Implications
Elevated G-CSF plasma levels with increased white blood cell counts correlate with significantly shorter survival in patients with malignancies, functioning as a negative prognostic biomarker 4.
Patients with G-CSF-producing tumors typically experience rapid and progressive fatal disease courses 3.
Critical Pitfalls to Avoid
Do not confuse iatrogenic granulocytosis from therapeutic G-CSF administration (used for chemotherapy-induced neutropenia prophylaxis) with paraneoplastic granulocytosis 8.
Recent growth factor therapy can obscure or mimic features of acute leukemia, making accurate diagnosis challenging 5.
The presence of granulocytosis in cancer patients does not automatically indicate infection or sepsis—consider paraneoplastic production, especially when accompanied by eosinophilia or when infection workup is negative 1, 2.
Immunohistochemical staining of tumor tissue for G-CSF or GM-CSF protein can confirm paraneoplastic production when the diagnosis is uncertain 1.