Paraneoplastic granulocyte colony-stimulating factor secretion in soft tissue sarcoma mimicking myeloproliferative neoplasia: a case report
- Christiane Dorn†1,
- Stefanie Bugl†1,
- Elke Malenke1,
- Martin R Müller1,
- Katja C Weisel1,
- Ulrich Vogel2,
- Marius Horger3,
- Lothar Kanz1 and
- Hans-Georg Kopp1Email author
© Dorn et al.; licensee BioMed Central Ltd. 2014
Received: 16 May 2013
Accepted: 19 May 2014
Published: 23 May 2014
While paraneoplastic leukocytosis is a common phenomenon in solid tumors, extreme elevations of white blood counts (WBC) in the range of more than 100,000/μl are uncommon in patients with non-hematologic malignancies. Leukocytosis with mature neutrophils due to a granulocyte colony-stimulating factor (G-CSF) producing tumor is only seen on rare occasions.
Massive neutrophil leukocytosis of approximately 100,000/μl was diagnosed in a 57-year-old Caucasian woman with metastatic undifferentiated endometrial sarcoma. A bone marrow trephine biopsy revealed massively increased granulopoiesis, but no evidence of monoclonal myeloproliferative disease. After the primary tumor had been resected, white blood count (WBC) plummeted and went back to nearly normal levels within one week. With progressive metastatic disease, granulocyte colony-stimulating factor (G-CSF) plasma levels were found to be increased by 10-fold. White blood count (WBC) strictly correlated with tumor burden and response to chemotherapy. In the final stage of treatment resistent disease, white blood count (WBC) approximated 300,000/μl.
We report on a granulocyte colony-stimulating factor (G-CSF) secreting undifferentiated endometrial sarcoma, which was associated with extreme neutrophil counts. White blood count (WBC) were closely correlated with tumor burden and associated with an aggressive clinical course. We suggest that paraneoplastic neutrophilia represents a poor prognostic sign in soft tissue sarcoma. In patients with similar constellations, antitumor therapy must not be delayed.
KeywordsParaneoplastic leukocytosis Neutrophilia G-CSF Sarcoma
Paraneoplastic leukocytosis is a common phenomenon in several different solid tumors. Affected patients typically have total white blood counts (WBC) between 12,000 and 30,000/μl with mainly mature neutrophil granulocytes .
Idiopathic extreme leukocytosis, also known as leukemoid reaction and defined as WBC ≥ 40,000/μl is rare in patients with non-hematologic malignancies: in the largest retrospective analysis of these uncommon patients, only 10% of cases were paraneoplastic in origin. Ninety-six percent of these patients had neutrophilia, and the mean WBC was 53,000/μl . A severe left shift, i.e. the presence of immature granulocytes such as myelocytes, promyelocytes, and blasts suggests myeloproliferative disorders, while paraneoplastic neutrophilia typically presents with mature neutrophils only. Leukocytosis with non-clonally derived mature neutrophils, due to paraneoplastic production of granulocyte colony-stimulating factor (G-CSF) is a rare phenomenon and has been described in a variety of different tumors [2, 3]. Most cases are associated with gastrointestinal, lung, or genitourinary carcinomas [4–8]. G-CSF producing tumors are typically poorly differentiated and patients are diagnosed in an advanced stage with a large tumor burden [9, 10]. Accordingly, disease outcomes are poor, which has been postulated to represent autocrine stimulation of tumor growth by G-CSF [11, 12]. In this article we report on a patient with a G-CSF producing undifferentiated endometrial sarcoma with massive neutrophil leukocytosis and an aggressive clinical course.
Differential blood counts after surgery
Day 0 2 h postop.
Day 3 postop.
WBC (μl −1 )
4.000 – 9.000
40 – 80
14.0 – 18.0
Platelets (μl −1 )
150.000 – 450.000
C-reactive protein (mg/dl)
In summary, this case demonstrates severe leukemoid reaction with pathologic left shift caused by a G-CSF secreting advanced undifferentiated endometrial sarcoma imitating hematologic malignancy.
Consistent with previously reported cases of paraneoplastic G-CSF secretion, leukemoid reaction was closely correlated with tumor burden and associated with an aggressive clinical course. To our knowledge, neutrophilic leukocytosis up to 200,000/μl and a severe left shift with massively increased G-CSF levels has not been reported before as a paraneoplastic phenomenon in sarcoma. We suggest not to delay antitumor treatment in patients with a similar constellation, but rather aggressively treat the underlying solid malignancy utilizing a response-inducing chemotherapy regimen.
Written informed consent was obtained from the patient herself before blood was drawn for G-CSF analysis. The patient agreed to publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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