about 30% of patients with a solid tumor have granulocytosis ( granulocyte count > 8,000/l ) . moreover , in about half of these patients with granulocytosis and cancer , the granulocytosis has an identifiable non - paraneoplastic etiology ( infection , tumor necrosis , glucocorticoid administration ) ; however , the others have no identifiable etiology of granulocytosis . it is well known that various types of nonhematopoietic tumors demonstrate granulocytosis of unknown cause without overt inflammation . recently , studies have demonstrated that such granulocytosis is due to hematopoietic growth factors , including granulocyte colony- stimulating factor ( g - csf ) , which are produced by the tumor . a variety of nonhematopoietic malignant tumors , including bladder cancer , hepatoma , mesothelioma , oropharyngeal cancer , melanoma , and sarcoma , have been reported to produce g - csf1 - 4 ) . granulocytosis occurs in 40% of patients with lung and gastrointestinal cancers , 20% of patients with breast cancer , 30% of patients with brain tumor and ovarian cancer and 10% of patients with renal cell carcinoma . however , carcinomas of uterine cervix producing these factors are extremely rare , although several cell lines producing il-6 , a pleiotropic cytokine , have been established from uterine cervical cancers5 ) . we report a case of uterine cervical cancer presenting with granulocytosis as a paraneoplastic syndrome . a 56-year - old woman was admitted to our hospital on december 22 , 2002 , complaining of vaginal spotting . colposcopic examination revealed a 5-cm sized cauliflower - like mass in the uterine cervix with upper vaginal invasion . microscopically , the biopsy specimen revealed a keratinizing type invasive squamous cell carcinoma ( figure 1 ) . there was a 5.53.5 cm high signal intensity mass in the uterine cervix with invasion of the left parametrium and a 1 cm lymph node in the left external iliac area on mri scan ( figure 2 ) . a blood sample showed the following findings : wbc , 12.710/l ( 78% neutrophils , 15% lymphocytes , 6% monocytes , 1% eosinophils ) ; rbc , 3.5410/l , hb , 8.7 g / dl , hct , 34.6% , platelets , 41310/l , c - reactive protein , 7.0 mg / dl , blood urea nitrogen , 13 mg / dl , creatinine , 0.6 g / dl , alkaline phosphatase , 207 iu / ml , ast , 29 iu / ml , alt , 8 iu / ml , and total protein , 7.4 g / dl . there was no evidence of hiv and hepatitis infection by serological studies . the radiological diagnosis was uterine cervical cancer stage iib , but physical examination revealed a movable cervix . consequently , she was assessed as a potential candidate for radical hysterectomy . considering potential resectability , we treated the patient with neoadjuvant chemotherapy with mvc regimen ( mitomycin - c 10 mg / m , vincristine 1.0 mg / m and cisplatin 70 mg / m ) every three weeks6 , 7 ) . after two cycles of treatment , the tumor size had increased as detected by a follow - up colposcopic examination . we performed a comprehensive evaluation of the newly developed severe leukocytosis , including blood culture , bone marrow aspiration and biopsy to rule out infection and hematological malignancy . there was no evidence of bone marrow involvement of malignant tumor ( figure 3 ) . furthermore , there was no specific infection or drug intake history , including steroid and herb medication . therefore , we considered the granulocytosis to be associated with the tumor itself . however , we could not determine the levels of g - scf , gm - csf , and il-6 in serum because the patient refused these lab tests . accordingly , we confirmed immunochemical expression of g - csf and il-6 by using paraffin block . staining for g - csf and il-6 was mainly observed in the cytoplasm of cancer cells ( figure 4a , 4b ) . we started external radiation for six weeks ( 4000 cgy ) , six cycles of chemotherapy with weekly cisplatin administration ( 40 mg / m ) , and two cycles of sequential intra - cavitary radiation ( icr ) . after these treatments , the cervical mass was no longer seen in the follow up mri scan ( figure 5 ) . the follow - up complete blood count profile revealed : wbc , 4,100/l ( 65% neutrophils , 15% lymphocytes , 16% monocytes ) ; rbc , 2.7710/l ; hb , 10.3 g / dl ; and platelets , 36610/l . one month later , a cavitary nodule was found in the left upper lobe of the lung in the chest x - ray , and a vulval mass was detected . both lesions were confirmed pathologically as metastatic squamous cell carcinoma by percutaneous needle aspiration cytology . at that time , the wbc count became elevated again to 29,600/l . , four cycles of this combination chemotherapy were carried out . after four cycles of treatment , a marked increase in metastatic lung nodules was found on the follow - up chest x - ray ( figure 6 ) , with severe granuocytosis ( 52,700/l ) . granulocytosis is caused by an exaggerated myeloid response to several stimuli , including infection , allergies , burns , intoxication , acute hemorrhage , malignant neoplasms , and certain drugs , including corticosteroids and lithium8 - 10 ) . malignant tumor - associated granulocytosis likely involves the secretion of hematopoietic growth factors such as g - csf , gm - csf and il-6 by the tumor . cervical cancer , like some other solid tumors , can also exhibit granulocytosis as a paraneoplastic syndrome . to rule out other causes of granulocytosis , extensive evaluation , including a careful assessment of patient history with particular attention to drug intake and a physical examination , should be performed . granulocytosis as a paraneoplastic syndrome usually involves carcinomas of the colon , lung , stomach , kidney , ovarian and bladder . the mechanism of ganulocytosis is possibly due to the secretion of g - csf by the tumor cells . g - csf is a cytokine secreted primarily by monocytes , macrophages , endothelial cells and fibroblasts . therefore , cancer patients with marked granulocytosis and without infection may have cytokine - producing tumors , and aggressive treatment should be considered . was mainly observed in the cytoplasm of cancer cells ( figure 4a , 4b ) . the relationship between cervical cancer and extreme granulocytosis followed by rapid normalization of the leukocyte count after treatment supports the possibility of autonomous production of g - csf by the tumor as the cause of marked granulocytosis in this case . the most important characteristic of this case was rapid tumor progression , which has been reported to be frequently observed in cytokine - producing tumors . a variety of nonhematopoietic malignant tumors have been demonstrated to secrete g - csf1 - 4 ) , and most of these patients had a poor clinical outcome . a few studies have shown that treatment of bladder cancer cell lines with exogenous g - csf in vitro results in enhanced tumor growth stimulation11 , 12 ) . therefore , we suggest that these malignant tumors should be regarded as aggressive and advanced disease , as they may have a high probability of poor response to treatment . furthermore , additional studies are needed to correlate the severity of paraneoplastic syndrome and disease progression or regression .
granulocytosis occurs in 40% of patients with lung and gastrointestinal cancers , 20% of patients with breast cancer , 30% of patients with brain tumor and ovarian cancer and 10% of patients with renal cell carcinoma . 
 granulocytosis occurs because of production of g - csf , gm - csf and il-6 . 
 uterine cervical carcinoma with granulocytosis as a paraneoplastic syndrome , however , has been rarely reported . 
 we recently witnessed a case of invasive squamous cell carcinoma of the uterine cervix with granulocytosis . 
 leukocytosis developed up to 69,000/l , and then normalized after chemo - radiotherapy . 
 there was no evidence of infection , tumor necrosis , glucocorticoid administration , or myeloproliferative disease by examination of a bone marrow aspirate when granulocytosis appeared . 
 this phenomenon was probably associated with the secretion of hematopoietic growth factors such as g - csf , gm - csf and il-6 by the tumor . 
 we suggest that , like some other solid tumors , cervical cancer can present with granulocytosis as a paraneoplastic syndrome .