Elevated Serum Granulocyte Colony-stimulating Factor Research Articles

18F-FDG PET/CT Imaging of G-CSF-Producing Inflammatory Myofibroblastic Tumor of the Pleura.

We report a case of granulocyte colony-stimulating factor (G-CSF)-producing inflammatory myofibroblastic tumor of the pleura in a 71-year-old man. Contrast-enhanced CT demonstrated multiple pleural masses with pulmonary hilar lymph nodes swelling. 18F-FDG PET/CT demonstrated marked focal FDG uptake in the thoracic masses with diffuse uptake in the bone marrow. Based on the pathological findings and elevated serum G-CSF level, the patient was diagnosed as G-CSF-producing inflammatory myofibroblastic tumor. Because G-CSF-producing tumors demonstrate aggressive clinical course, early and accurate diagnosis is important.

Rapid progression of a granulocyte colony-stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: A case report and literature review.

The current study presents the case of a 72-year-old woman with a rapidly enlarged liver metastasis from esophagogastric junction (EGJ) cancer, accompanied by progressive leukocytosis (47,680/µl) and elevated serum granulocyte colony-stimulating factor (G-CSF; 779 pg/ml). The patient underwent right hemihepatectomy 26 months after a total gastrectomy. On the seventh post-operative day the patient's leukocyte count and serum G-CSF level decreased to 4,280/µl and ≤19.5 pg/ml, respectively. Histologically, the lesion was a well to moderately differentiated adenocarcinoma similar to the primary lesion. Therefore, this tumor was clinically diagnosed as a G-CSF-producing liver metastasis from EGJ cancer, although immunohistochemical staining for G-CSF was negative. A right pulmonary nodule detected simultaneously with the hepatic mass was resected four months following the hepatectomy and was diagnosed as a pulmonary metastasis. The patient's leukocyte count was normal at the time of her initial surgery for EGJ cancer, and her clinical course varied for different metastatic sites. The liver metastasis was accompanied by progressive leukocytosis and elevated serum G-CSF and demonstrated rapid tumor growth during a six-month period, whereas the non-G-CSF-producing pulmonary metastasis grew slowly during the same period. In addition 21 reported cases of G-CSF-producing upper gastrointestinal tract cancer were reviewed to elucidate the clinicopathological features of this disease.

Neonatal Leukemoid Reaction with Fetal Inflammatory Response Syndrome Is Associated with Elevated Serum Granulocyte Colony Stimulating Factor and Interleukin-6.

Leukemoid reaction (LR) is a reactive disease that exhibits abnormal blood values similar to leukemia, but not due to leukemia. One report showed that neonatal LR (NLR) was associated with elevated serum granulocyte colony stimulating factor (G-CSF) in only 30% of the study neonates. NLR is not always associated with the elevation of serum G-CSF. NLR was defined as a white blood cell count of ≥ 40 × 103/μL and/or blast cell concentration of > 2%. We have focused on NLR with fetal inflammatory response syndrome (FIRS), defined as a fetal systemic inflammatory reaction triggered by intrauterine infection. FIRS was diagnosed based on a cord serum interleukin-6 (IL-6) concentration ≥ 17.5 pg/mL and histopathological chorioamnionitis. Because NLR is highly associated with FIRS, we have hypothesized that NLR is associated with the elevation of both G-CSF and IL-6. This is the first report to measure multiple cytokines in NLR at the same time. The study comprised 19 preterm infants with FIRS: 8 with NLR (study group) and 11 without NLR (control group). Serum G-CSF and IL-6 concentrations were significantly higher in the study group than the control group. There was a positive correlation between G-CSF and IL-6 levels in the study group but not in the control group. These results suggest that elevated serum G-CSF and IL-6 may underlie NLR. Thus, G-CSF and IL-6 concentrations may be predictive of the onset of NLR. Measuring these cytokines is useful for judging the prognosis of preterm infants and for their post-natal clinical management.

Granulocyte-colony stimulating factor producing anaplastic carcinoma of the pancreas treated by distal pancreatectomy and chemotherapy: report of a case.

Granulocyte-colony stimulating factor (G-CSF) producing pancreatic cancers are extremely rare. These tumors have an aggressive clinical course but no established treatment. We encountered a patient with a G-CSF-induced pancreatic cancer who was treated by surgical resection, followed by steroid treatment and chemotherapy. A 68-year-old Asian male presented at a local hospital with a 3-month history of fever, loss of appetite, and 10-kg weight loss. Laboratory data showed leukocytosis and elevation of C-reactive protein. Computed tomography (CT) revealed a 50-mm mass in the tail of the pancreas, but no signs of infective foci. He was transferred to our hospital for further evaluation. Contrast-enhanced CT showed rapid growth of this tumor over 1 week, and 18 F-2-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) showed FDG accumulation in the tail of the pancreas (SUV max, 17.1) but at no other sites in his body. Magnetic resonance imaging showed a heterogeneous mass, similar to that observed by CT. Three weeks later, the patient underwent a distal pancreatectomy with splenectomy. The resected specimen was 154 mm in diameter, a threefold increase from the initial image. Histopathological examination identified the tumor as an anaplastic carcinoma of the pancreas. Following surgery, his leukocyte count and body temperature were reduced. He recovered well and was discharged from our hospital on postoperative day 18. Immunohistochemical expression of G-CSF in the resected specimen and elevated serum G-CSF concentration confirmed that the mass was a G-CSF producing anaplastic carcinoma of the pancreas. Subsequently, the patient experienced a high fever and loss of appetite. CT showed recurrence of cancer in the abdominal cavity, for which he was started immediately on tegafur-gimeracil-oteracil potassium combination S-1 and steroid. Unfortunately, he died on postoperative day 83. To our knowledge, this patient was the first with a G-CSF producing anaplastic carcinoma of the pancreas to be treated by surgical resection, steroid and adjuvant chemotherapy.

Abstract 1103: MDSC targeting therapy for uterine cervical cancer displaying TRL

Abstract Objectives: The aim of this study was to investigate the clinical implications and underlying mechanism of tumor-related-leukocytosis (TRL) in cervical cancer. Methods: The clinical data of cervical cancer patients who were treated with definitive radiotherapy were analyzed to investigate the association between TRL and treatment outcome in retrospective and prospective settings. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were employed to examine the mechanisms responsible for TRL in cervical cancer, focusing on the myeloid-derived suppressor cell (MDSC) and tumor-derived granulocyte colony-stimulating factor(G-CSF). Results: TRL was significantly associated with shorter survival. The TRL-positive patients displayed upregulated tumor G-CSF expression and elevated serum G-CSF levels and increased MDSC frequencies in the blood compared with the TRL-negative patients. In vitro and in vivo investigations revealed that tumor-derived G-CSF is involved in the underlying causative mechanism of TRL and that the increase in the number of MDSC induced by tumor-derived G-CSF is responsible for the rapidly progressive nature of TRL-positive cervical cancer. The administration of anti-Gr-1 antibody or the depletion of MDSC by splenectomy significantly inhibited tumor growth in TRL-positive cervical cancer. Conclusion: TRL is an indicator of a poor prognosis in cervical cancer patients treated with definitive radiotherapy. MDSC induced by tumor-derived G-CSF is responsible for the rapidly progressive nature of TRL-positive cervical cancer. MDSC-targeting treatments might have therapeutic potential in TRL-positive cervical cancer. Note: This abstract was not presented at the meeting. Citation Format: Yuri Matsumoto, Mahiru Kawano, Tomoyuki Sasano, Seiji Mabuchi. MDSC targeting therapy for uterine cervical cancer displaying TRL. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2014-1103

Uterine cervical cancer displaying tumor-related leukocytosis: a distinct clinical entity with radioresistant feature.

Tumor-related leukocytosis (TRL) is occasionally found in patients with nonhematopoietic malignancies. We investigated the clinical implication of TRL and individualized treatment for TRL-positive cervical cancer, as well as the underlying biological mechanism. Clinical data from 258 cervical cancer patients treated with definitive radiotherapy were analyzed to investigate the association between TRL and treatment outcome. Clinical samples, cervical cancer cell lines, and a mouse model of cervical cancer were used to examine the mechanisms responsible for TRL in cervical cancer, focusing on the role of tumor-derived granulocyte colony-stimulating factor (G-CSF) and myeloid-derived suppressor cells (MDSCs). All statistical tests were two-sided. TRL was statistically significantly associated with younger age (Wilcoxon rank sum test, P = .03), larger tumor size (Wilcoxon rank sum test, P = .006), advanced clinical stage (χ(2) test, P = .01), and shorter overall survival (Cox proportional hazard modeling and Wald tests, P < .001). Among cervical cancer patients, TRL was associated with upregulated tumor G-CSF expression (χ(2) test, P < .001), elevated serum G-CSF levels (Student t test, P = .03), larger spleens (Student t test, P = .045), and increased MDSC frequencies in the blood (Student t test, P < .001) compared with the TRL-negative patients. In vitro and in vivo experiments revealed that tumor-derived G-CSF was involved in the underlying causative mechanism of TRL and MDSCs induced by tumor-derived G-CSF are responsible for the rapidly progressive and radioresistant nature of TRL-positive cervical cancer. The administration of anti-Gr-1 neutralizing antibody or the depletion of MDSCs by splenectomy (n = 6 per group) inhibited tumor growth and enhanced radiosensitivity in TRL-positive cervical cancer xenografts (Wilcoxon rank sum test, P = .008 and P = .02, respectively). TRL is associated with resistance to radiotherapy among cervical cancer patients, and MDSC-targeting treatments may have therapeutic potential in these patients.

G-CSF producing pleomorphic carcinoma with undetected origin: an autopsy case report

Pleomorphic carcinoma is an uncommon neoplasm that is known to arise in diverse sites, including the lung, breast, pancreas, gallbladder and prostate. We encountered a rare case of pleomorphic carcinoma of undetected origin associated with production of granulocyte-colony stimulating factor (G-CSF). The patient was a 62-year-old man who presented with cough and general fatigue. Chest computed tomography (CT) demonstrated a mass lesion in the mediastinum, so mediastinoscopic tumor biopsy was performed. However, making the diagnosis was difficult despite the suspected malignant potential. CT-supported positron emission tomography showed multiple uptake lesions in the small intestine, duodenum and right adrenal gland, in addition to the mediastinum. The patient subsequently presented with right-side weakness and sensory impairment. Brain CT showed multiple intracerebral lesions, indicating metastatic tumors. For the definitive diagnosis and to clarify options for chemotherapeutic management, the patient underwent surgical craniotomy. The resected specimen was considered to represent sarcomatoid carcinoma with positive immunoreactive staining for cytokeratin as an epithelial marker, indicating pleomorphic carcinoma. Furthermore, laboratory data showed leukocytosis without any infections and elevated serum G-CSF levels during hospitalization. The patient developed complications of occlusive intussusception in the small intestine caused by probably metastatic lesions and died from disease progression 82 days after initial admission. Although the presence of G-CSF-producing pleomorphic carcinoma was confirmed, the primary origin of this pleomorphic carcinoma could not be indentified clearly even at autopsy.

Granulocyte‐colony stimulating factor‐producing cervical cancers treated with carbon‐ion irradiation

Granulocyte-colony stimulating factor (G-CSF)-producing tumor is a rare condition. It has an aggressive nature and shows resistance to conventional treatments. We report two cases of G-CSF-producing uterine cervical cancer who were successfully treated with carbon-ion radiotherapy (C-ion RT). The first case was a 76-year-old woman with stage IIIB uterine cervical cancer, and the second was a 75-year-old woman with bulky stage IIB disease. Prior to treatment, both patients presented severe granulocytosis and elevated serum G-CSF concentrations. After C-ion RT, their cervical tumors completely disappeared, and their granulocytosis and elevated serum G-CSF levels improved as well. C-ion RT has been reported to be effective for various aggressive tumors, and it may be a good treatment option for this rare aggressive tumor.

Radioprotective effects of oral 17-dimethylaminoethylamino-17-demethoxygeldanamycin in mice: bone marrow and small intestine

BackgroundOur previous research demonstrated that one subcutaneous injection of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) 24 hours (h) before irradiation (8.75 Gy) increased mouse survival by 75%. However, the protective mechanism of 17-DMAG is currently unknown. The present study aimed to investigate whether oral administration of 17-DMAG was also radioprotective and the potential role it may play in radioprotection.ResultsA single dose of orally pre-administered (24, 48, or 72 h) 17-DMAG (10 mg/kg) increased irradiated mouse survival, reduced body weight loss, improved water consumption, and decreased facial dropsy, whereas orally post-administered 17-DMAG failed. Additional oral doses of pre-treatment did not improve 30-day survival. The protective effect of multiple pre-administrations (2−3 times) of 17-DMAG at 10 mg/kg was equal to the outcome of a single pre-treatment. In 17-DMAG-pretreated mice, attenuation of bone marrow aplasia in femurs 30 days after irradiation with recovered expressions of cluster of differentiation 34, 44 (CD34, CD44), and survivin in bone marrow cells were observed. 17-DMAG also elevated serum granulocyte-colony stimulating factor (G-CSF), decreased serum fms-related tyrosine kinase 3 ligand, and reduced white blood cell depletion. 17-DMAG ameliorated small intestinal histological damage, promoted recovery of villus heights and intestinal crypts including stem cells, where increased leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) was found 30 days after irradiation.Conclusions17-DMAG is a potential radioprotectant for bone marrow and small intestine that results in survival improvement.

Granulocyte-colony stimulating factor-producing squamous cell carcinoma arising in ovarian mature cystic teratoma: A case report

Granulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs. It has an aggressive nature and shows resistance to conventional treatments, however, its clinical features are not well known because of the small number or reported cases. We report G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma. An 80-year-old woman underwent suboptimal surgical excision of stage IIIC ovarian cancer. Prior to the treatment, the patient presented severe granulocytosis and elevated serum G-CSF concentration. With the help of histopathological and immunohistochemical studies, we diagnosed this case to be a poorly differentiated squamous cell carcinoma developed in ovarian mature cystic teratoma, which highly expressed G-CSF. During radiation therapy, the patient died from rapid growth of residual tumor and peritoneal dissemination 2 months after surgery. This is the first case of G-CSF-producing squamous cell carcinoma arising in malignant-transformed ovarian mature cystic teratoma, and its prognosis was very poor.

Uterine Leiomyosarcoma Producing Granulocyte Colony Stimulating Factor

Uterine leiomyosarcoma associated with the paraneoplastic production of granulocyte-colony stimulating factor (GCSF) is extremely rare. No case has been reported to date in the English literature. We describe a case of a 56-year-old female with recurrent uterin leiomyosarcoma, associated with leukocytosis (19100/mm) and an elevated serum GCSF (33.0 pg/ml). Tumore histology was consistent with a well differentiated leiomyosarcoma with marked neutrophilic infiltration of the lung and spleen metastases. tumor cells were distinctly positive for GCSF on immunohistochemistry. These findings confirmed the diagnosis of a GCSF-producting uterine leiomyosarcoma with a paraneoplastic leukocytosis.

Anaplastic Transformation of Follicular Thyroid Carcinoma in a Metastatic Skeletal Lesion Presenting with Paraneoplastic Leukocytosis

Anaplastic transformation of differentiated thyroid carcinoma (DTC) is a rare event with a poor clinical outcome. It usually occurs in the primary site or in regional lymph nodes, but rarely in distant metastatic lesions. A 55-year-old woman with persistent pain in the left hip joint visited our hospital. She had a history of DTC that had been surgically removed 12 years earlier. Clinical images showed a tumorous mass in the left pelvis, indicative of bone metastasis. The patient underwent surgery to remove the tumor and remained stable until local recurrence was found 5 weeks after the surgery. The patient subsequently underwent radiation therapy; however, she died of respiratory failure due to lung metastases 2 months after the surgery for the recurrent lesion. The surgical specimens were diagnosed as anaplastic thyroid carcinoma, indicating that anaplastic transformation of thyroid follicular carcinoma occurred in the metastatic skeletal lesion. In addition, the patient had an unusually high white blood cell count throughout the course. Based on elevated serum granulocyte colony-stimulating factor (G-CSF) levels and positive immunostaining for G-CSF in the surgical specimens, the patient was diagnosed with paraneoplastic leukocytosis. To our knowledge, this is the first case of anaplastic transformation of DTC arising in a metastatic bone lesion described in the literature. In addition, the present case also exhibited severe leukocytosis accompanied by elevated serum G-CSF levels. Clinicians should be aware of the possibility of this occurring in their patients with DTC, as this development calls for a rapid change from observational follow-up to aggressive treatment.

Leiomyosarcoma in the humerus with leukocytosis and elevation of serum G-CSF

Leukocytosis associated with secretion of granulocyte colony-stimulating factor (G-CSF) has been reported in various tumors, primarily poorly differentiated epithelial tumors, but is extremely rare in bone tumors. An 84-year-old woman experienced swelling and pain in the shoulder for 1month. Leukocytosis and elevated serum G-CSF were observed, but resolved following tumor resection. A diagnosis of leiomyosarcoma of the bone with expression of G-CSF was confirmed immunohistochemically. Histological diagnosis of leiomyosarcoma showed it to be differentiated, which is unusual for G-CSF-secreting tumors.

Pleomorphic carcinoma of the lung producing granulocyte colony-stimulating factor: Report of a case

We herein report a case of acute respiratory distress syndrome (ARDS) that appeared to be related to a granulocyte colony-stimulating factor (G-CSF)-producing lung cancer. A 77-year-old man with arterial sclerotic obstruction (ASO) underwent reconstructive surgery of the left femoral artery. He developed ARDS on the 5th postoperative day, which resolved following mechanical ventilation with steroid pulse treatment. Four months later, he was admitted with a fever and right arm pain. Chest computed tomography showed a malignant lesion in the right apical lung, and percutaneous needle biopsy demonstrated adenocarcinoma. Laboratory data revealed neutrophilia with elevated serum G-CSF levels. He underwent a right upper lobectomy with chest wall resection, and administration of sivelestat sodium to treat his postoperative pre-acute lung injury state. Pathology revealed a G-CSF-producing pleomorphic carcinoma. Retrospectively, a tumor shadow was noted on chest X-ray at the time of ARDS just after ASO surgery. The relationship between an abnormal G-CSF level and ARDS was considered, and the implications are herein discussed.

CNS-targeted Viral Delivery of G-CSF in an Animal Model for ALS: Improved Efficacy and Preservation of the Neuromuscular Unit

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motoneurons. We have recently uncovered a new neurotrophic growth factor, granulocyte-colony stimulating factor (G-CSF), which protects α-motoneurons, improves functional outcome, and increases life expectancy of SOD-1 (G93A) mice when delivered subcutaneously. However, chronic systemic delivery of G-CSF is complicated by elevation of neutrophilic granulocytes. Here, we used adeno-associated virus (AAV) to directly target and confine G-CSF expression to the spinal cord. Whereas intramuscular injection of AAV failed to transduce motoneurons retrogradely, and caused a high systemic load of G-CSF, intraspinal delivery led to a highly specific enrichment of G-CSF in the spinal cord with moderate peripheral effects. Intraspinal delivery improved motor functions, delayed disease progression, and increased survival by 10%, longer than after systemic delivery. Mechanistically, we could show that G-CSF in addition to rescuing motoneurons improved neuromuscular junction (NMJ) integrity and enhanced motor axon regeneration after nerve crush injury. Collectively, our results show that intraspinal delivery improves efficacy of G-CSF treatment in an ALS mouse model while minimizing the systemic load of G-CSF, suggesting a new therapeutic option for ALS treatment.

Paraneoplastic granulocytosis in metastatic melanoma

Paraneoplastic syndromes are an uncommon, yet well-described, phenomenon in cancer patients. The syndrome of granulocytosis caused by granulocyte colony-stimulating factor (G-CSF) production by tumors is rare and is difficult to diagnose in patients receiving treatment for metastatic disease. From January 2005 to May 2009, 626 patients were evaluated for treatment of metastatic melanoma. At initial evaluation or during the course of treatment, six patients had an elevated white blood cell count and no evidence of infection. All six had significantly elevated serum G-CSF. The level of serum G-CSF was directly correlated with the absolute neutrophil count. In-vitro assay of melanoma tumor from two patients showed elevated G-CSF in cell culture supernatant. The paraneoplastic syndrome of granulocytosis resulting from ectopic G-CSF production in patients with metastatic melanoma is rare. This diagnosis should be considered when common causes of granulocytosis have been ruled out.

A Case of Granulocyte-Colony Stimulating Factor-Producing Hepatocellular Carcinoma Confirmed by Immunohistochemistry

Granulocyte-colony stimulating factor (G-CSF) is a naturally occurring glycoprotein that stimulates the proliferation and maturation of precursor cells in the bone marrow into fully differentiated neutrophils. Several reports of G-CSF-producing malignant tumors have been published, but scarcely any in the hepatobiliary system, such as in hepatocellular carcinoma (HCC). Here, we encountered a 69-yr-old man with a hepatic tumor who had received right hepatic resection. He showed leukocytosis of 25,450/µL along with elevated serum G-CSF. Histological examination of surgical samples demonstrated immunohistochemical staining for G-CSF, but not for G-CSF receptor. The patient survived without recurrence for four years, but ultimately passed away with multiple bone metastases. In light of the above, clinicians may consider G-CSF-producing HCC when encountering patients with leukocytosis and a hepatic tumor. More cases are needed to clarify the clinical picture of G-CSF-producing HCC.

Characteristic EUS and FDG-PET features of G-CSF Producing Esophageal Squamous Cell Carcinoma: A Case Report and Review of the Literature

Purpose: Tumors producing granulocyte colony stimulating factor (G-CSF) are quite rare, and features of clinical examinations are not well known. Particularly in G-CSF producing esophageal tumors, only a few reports are available concerning EUS and FDG-PET features. Methods: We present a case of G-CSF producing esophageal squamous cell carcinoma showing interesting features of EUS and FDG-PET imaging findings, and changes of clinical examinations with a treatment course were analyzed. Results: A 58-year-old Japanese man had type I esophageal cancer with marked lymph node metastases associated with leukocytosis and elevated serum G-CSF, IL-6, CRP, and SCC. Repeated biopsy showed poorly differentiated squamous cell carcinoma, not carcinosarcoma. Although the primary lesion was negative for G-CSF by immunohistochemistry, a highly increased G-CSF m-RNA level, measured using reverse transcriptase-polymerase chain reaction in frozen sections, led to a diagnosis of GCSF-producing esohageal cancer. Before treatment, esophagoscopy showed 5 cm tumor with a steep slope in the middle thoracic esophagus, and EUS showed a low echoic mass with the mixture of a high echoic area in the 1st∼3rd layer. Contrary to the tumor size, the depth of tumor invasion was relatively shallow, T1 (SM with massive invasionor), or T2 (MP with slight invasion). FDG-PET scanning showed a significantly high uptake in the main tumor, abdominal lymph nodes and the bones. Uptake in the bone was symmetrically found in the red pulp throughout the body. This patient was diagnosed as stage 4 esophageal squamous cell carcinoma and received 1st line chemotherapy with 5-FU and cisplatin. This regimen led to progressive disease and worse performance status. He selected another chemotherapy, not best supportive care, and 2nd line treatment with irrinotecan monotherapy enabled partial response during five months. He died 10 months after the 2nd line chemotherapy with irrinotecan due to the progression of tumors. Throughout the treatment course, FDG uptake in the bone changed along with the change of the leukocytes, serum G-CSF, IL-6, CRP and SCC. Conclusion: When detecting esophageal tumor with a steep slope, serum G-CSF, IL-6, and CRP must be checked in consideration of G-CSF producing cancer. EUS and FDG-PET attribute to the diagnosis. Irrinotecan monotherapy can be one of the effective regimens for non-operable G-CSF producing esophageal cancer.

Carcinosarcoma of the gallbladder producing α-fetoprotein and manifesting as leukocytosis with elevated serum granulocyte colony-stimulating factor: Report of a case

A 69-year-old man was referred to our hospital for investigation of leukocytosis and a persistent fever of 38 degrees C, but we could find no evidence of a specific infection. The leukocyte count was 18,000/mm(3), and the serum granulocyte colony-stimulating factor (G-CSF) and alpha-fetoprotein (AFP) levels were both elevated, at 66.3 pg/ml and 1,495 ng/ml, respectively. Computed tomography (CT) showed a gallbladder tumor and we performed extended cholecystectomy. Postoperatively, the fever subsided and the leukocyte count, serum G-CSF and AFP level normalized. Histologically, the tumor was a carcinosarcoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for AFP, but negative for G-CSF. This is the first report of a carcinosarcoma of the gallbladder producing AFP. The laboratory findings and clinical course strongly suggested that the tumor produced not only AFP, but also G-CSF.

Elevated Granulocyte Colony-Stimulating Factor, Non-Infectious Leukocytosis and Fevers in a Patient with Multiple Myeloma

We report the case of a 56-year-old male with multiple myeloma in whom recurrent fevers and leukocytosis delayed potentially effective chemotherapy due to concern for active infection. A thorough infectious workup, including CT and PET scans, was negative. The patient was eventually found to have an elevated serum granulocyte colony-stimulating factor (G-CSF) of 113 pg/ml (normal range 0.0 - 39.1 pg/ml), which was likely the cause of his persistent leukocytosis and fevers. Multiagent chemotherapy was initiated, and the fevers resolved in the next 4 days. Leukocyte concentrations trended down after initiation of chemotherapy, but it is uncertain how much of the decline was attributable to immunosuppression. We report this well-documented case to demonstrate that G-CSF production should be considered as a cause of unexplained fever and leukocytosis in patients with multiple myeloma to prevent inappropriate and delayed definitive diagnosis and treatment.