The leukocytosis seen in the current case with dedifferentiated liposarcoma seemed to be due to stimulation by the tumor-produced G-CSF, on the basis that both the leukocytosis and the elevated level of G-CSF disappeared after the tumor was resected. In a previous report, leukocytosis appeared at an advanced stage, as characterized by poorly differentiated adenocarcinoma, not in the early stage, as characterized by well-differentiated adenocaricnoma, in the same lesion of gastric cancer. In that gastric cancer case, immunopositivity of G-CSF was only seen in the poorly differentiated adenocarcinoma, not in the well-differentiated adenocarcinoma. It is thus possible that histological changes may influence the acquisition of G-CSF-producing ability [7
]. In the current study, immunohistochemical study failed to detect any expression of G-CSF. It would seem that G-CSF-producing ability was acquired during the course of tumor progression, because leukocytosis appeared after noticeable tumor growth. It is also possible that the components of G-CSF-producing cells are heterogeneous in the tumor. Neoplastic cells in unexamined histological sections may express G-CSF, and an immunohistochemical study would have detected G-CSF expression.
In the English literature, including the current case, there have been 6 cases of liposarcoma accompanied by leukocytosis and associated with G-CSF expression [8
]. Gender distribution was 3 males and 3 females, while the average age was 64.7 (range; 50–77) years. The sites were the following; retroperitoneum in 4 cases, mesenterium in 1 case and upper arm in 1 case. The subtype of these liposarcoma cases was dedifferentiated liposarcoma in 4 cases [10
] and pleomorphic liposarcoma in 2 cases [8
]. Pleomorphic liposarcoma showed the features of pleomorphic sarcoma, mimicking MFH, and at least focally contained typical multivacuolated lipoblasts. In the case of epithelial tumors, G-CSF-producing tumors have been reported to be associated with poor differentiation [1
]. Up until now, there have been no reported cases of well-differentiated liposarcoma with leukocytosis. Therefore, it may also be true that G-CSF expression is associated with undifferentiated liposarcoma, including both dedifferentiated liposarcoma and pleomorphic liposarcoma. Furthermore, it might be better to search for dedifferentiated components in an effort to provide a possible diagnosis of dedifferentiated liposarcoma, when well-differentiated liposarcoma is accompanied by leukocytosis.
MFH has been reported to be accompanied by leukocytosis, previously [4
]. The diagnostic criteria of MFH are defined as "pleomorphic spindle cell sarcoma with no distinct line of differentiation". The diagnosis of MFH is commonly made by exclusion of other definitive sarcomas, such as liposarcoma and leiomyosarcoma. Recently, after reassessment of pleomorphic sarcomas, the tumors in a certain number of cases have been proved to be specific sarcomas other than MFH. Therefore, there is the possibility that the reported case of MFH with leukocytosis actually had a liposarcoma lineage. In addition, among soft-tissue tumors with specific differentiation, there seem to be no reported cases with leukocytosis, besides liposarcoma. The association between G-CSF production and undifferentiated liposarcoma formation implies that they share the same signaling pathways in part.
In epithelial cancers, G-CSF expression has been associated with poor differentiation and invasiveness [1
]. Moreover, G-CSF expression was reported to be linked to poor prognosis in patients with lung carcinoma [13
]. G-CSF has been shown to stimulate tumor cell growth and migration in vitro [14
]. In a similar manner, G-CSF may have contributed to the aggressive behavior of dedifferentiated liposarcoma in the current case. A transcription factor STAT3 is a key mediator of G-CSF signaling. STAT3 potently promotes proliferation, survival, invasion and angiogenic effects through regulation of multiple gene products [18
]. Survivin is one of the STAT3-regulated genes, and has an important function in regulating the growth of cancer cells [22
]. It has been indicated that G-CSF potently activates STAT3 and STAT3-dependent survivin expression in bladder cancer cells [23
]. Further examination would be necessary to confirm whether or not this mechanism holds true for liposarcoma.