Neutrophilia Associated with Anaplastic Carcinoma of the Thyroid: Production of Macrophage Colony-Stimulating Factor (M-CSF) and lnterleukin-6

Abstract

Cancers associated with marked neutrophilia are relatively rare. We report here two cases of anaplastic thyroid carcinoma associated with neutrophilia. We measured the concentrations of granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in sera, pleural effusion, cyst fluid of the thyroid carcinoma region, or culture supernatants of carcinoma cells. Maximum levels of elevated white blood cell counts reached 106.1 x 10(9)/L (neutrophils 103.0 x 10(9)/L) in case 1 and 62.3 x 10(9)/L (neutrophils 57.9 x 10(9)/L) in case 2. Acute-phase reactants were elevated to various degrees, and hypercalcemia was found in both cases. IL-6, G-CSF, and M-CSF seemed to play the principal roles in neutrophilia in case 1, and the elevated levels of IL-6 and M-CSF seemed to mainly contribute to neutrophilia in case 2. Immunohistochemical staining revealed that carcinoma cells themselves produce IL-6 regardless of the types of carcinoma cells. To our knowledge, this is the first report describing the contribution of M-CSF to neutrophilia in patients with thyroid carcinoma.

Production of multiple cytokines and induction of cachexia in athymic nude mice by a new anaplastic thyroid carcinoma cell line

“…Trace amounts of TNF-(,5 pg/ml) were detected in only two ATC cell cultures (Aust et al 1996, Sato et al 2000. Thena cells might be the first thyroid carcinoma cells reported to produce high TNF-in vitro.…”

Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating factor is associated with neutrophilia and eosinophilia

“…Most of the reported patients with thyroid tumors and paraneoplastic leukocytosis had neutrophilia, [11][12][13][14]17 few had eosinophilia, [19][20][21][22] and only one had both neutrophilia and eosinophilia, 15 as the patient we describe. Production of colony-stimulating factors, such as G-CSF, [13][14][15] GM-CSF 15,16 and M-CSF 17 by the tumor, has been related to paraneoplastic leukocytosis, although the mechanism of induction of this haematologic abnormality remains unknown.…”

“…[11][12][13][14][15][16][17] Only two patients with differentiated thyroid cancer have thus far been reported, one with papillary type associated with neutrophilia 18 and one with medullary type associated with eosinophilia. 19 We report a patient with metastatic thyroid papillary carcinoma, in whom marked neutrophilia and eosinophilia and high circulating levels of GM-CSF were detected.…”

A Case of Thyroid Anaplastic Carcinoma Presenting Marked Neutrophilia and Eosinophilia due to Co-Production of GM-CSF, M-CSF and IL-6

“…Case reports of CSF-producing thyroid carcinoma with leukocytosis have been listed in Table 2. Within these reports, histological type was anaplastic carcinoma in 11 of 14 cases [4][5][6][7][8][9][10][11][12][13][14][15][16]. Anaplastic carcinoma might sometimes have a possibility of production of CSF.…”