Primary squamous cell carcinoma of the thyroid associated with marked leukocytosis and hypercalcemia

Saito, Koshi; Kuratomi, Yasuko; Yamamoto, Kunihiro; Saito, Toshikazu; Kuzuya, Tsunehiko; Yoshida, Sho; Moriyama, Shinichi; Takahashi, Atsushi

doi:10.1002/1097-0142(19811101)48:9<2080::aid-cncr2820480927>3.0.co;2-n

Cited by 83 publications

(29 citation statements)

References 21 publications

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“…In addition to cachexia and hypercalcemia, leukocytosis is also a relatively common paraneoplastic syndrome (5). In recent years, a number of studies have noted the association between leukocytosis and hypercalcemia (6)(7)(8)(9)(10), and several factors including colony-stimulating factors for granulocytes (G-CSF),' for granulocyte-macrophages (GM-CSF), and for macrophages (M-CSF) and bone resorbing factors (7)(8)(9) have been implicated in the pathogenesis of the leukocytosis-hypercalcemia syndrome.…”

Section: Introductionmentioning

confidence: 76%

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

Yoneda¹,

Alsina²,

Chavez³

et al. 1991

J. Clin. Invest.

118

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Recently, we have established a human squamous cell carcinoma of the maxilla (called MH-85) associated with hypercalcemia, leukocytosis, and cachexia in culture. MH-85 tumor cells caused the same paraneoplastic syndromes in tumor-bearing nude mice. We found that there was a sixfold increase in splenic size in MH-85 tumor-bearing mice. This increase paralleled tumor growth and was reversed by surgical removal of the tumor. Splenectomy in nude mice 1 wk before or 6 wk after tumor inoculation resulted in a decrease in tumor growth, and impairment of hypercalcemia, leukocytosis, and cachexia. In MH-85 tumor-bearing animals that had been pretreated by splenectomy, intravenous injection of fresh normal spleen cells caused an immediate reversal of leukocytosis, hypercalcemia, and cachexia. Since the presence of cachexia in both the patient and the mice carrying the tumor suggested tumor necrosis factor (TNF) may be overproduced, we injected polyclonal neutralizing antibodies raised against murine TNF into tumor-bearing mice. There was a rapid and reproducible decrease in blood ionized calcium, accompanied by suppression of osteoclast activity. No changes in blood ionized calcium were seen in mice injected with normal immune sera. In addition, there was an increase in body weight and decrease in white cell count. Plasma immunoreactive TNF was increased almost fourfold in tumor-bearing nude mice compared with control nude mice. Although TNF activity was undetectable in MH-85 culture supernatants, cells of the macrophage lineage, including spleen cells, released increased amounts of TNF when cultured with MH-85 tumor-conditioned media. These results suggest that splenic cytokines such as TNF may influence the development of the paraneoplastic syndromes of hypercalcemia, leukocytosis, and cachexia in these animals, as well as tumor growth. They also show that paraneoplastic syndromes may be due to factors produced by normal host cells stimulated by the presence of the tumor. (J. Clin. Invest. 1991. 87:977-985.)

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Section: Introductionmentioning

confidence: 76%

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

Yoneda¹,

Alsina²,

Chavez³

et al. 1991

J. Clin. Invest.

118

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“…[1][2][3][4][5][6][7][8][9][10] The production of granulocyte colony-stimulating factor (G-CSF) or parathyroid hormone-related protein (PTHrP) by cancer cells is thought to be responsible for these paraneoplastic syndromes. [11][12][13][14][15][16] However, it remains unknown whether simultaneous occurrence of hypercalcemia and leukocytosis is coincidental or not.…”

mentioning

confidence: 73%

“…1,2,28,29) The production of G-CSF and PTHrP by cancer cells is thought to be responsible for these paraneoplastic syndromes. However, the mechanism of simultaneous and unrestricted production of G-CSF and PTHrP by cancer cells is not well delineated.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Granulocyte Colony‐stimulating Factor and Parathyroid Hormonerelated Protein Production in Lung Carcinoma Cell Line OKa‐C‐1

Uemura

Nakata

Kobayashi

et al. 2000

Japanese Journal of Cancer Research

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Previously we have established a clonal squamous cell carcinoma cell line OKa‐C‐1 derived from lung cancer of a patient with marked leukocytosis and hypercalcemia. OKa‐C‐1 cells simultaneously produce granulocyte colony‐stimulating factor (G‐CSF) and parathyroid hormone‐related protein (PTHrP) at the single cell level and cause paraneoplastic syndromes in nude mice bearing the tumor. It is known that the production of G‐CSF and PTHrP is individually regulated by inflammatory cytokines in various malignant cells. To investigate the common factors in the regulation of G‐CSF and PTHrP production in OKa‐C‐1 cells, we examined the effects of some inflammatory agents [lipopolysaccharide (LPS), phorbol‐12‐myristate‐13‐acetate (PMA), tumor necrosis factor‐α (TNF‐α), interleukin‐1 (IL‐1) β and IL‐6] on G‐CSF and PTHrP production, by means of enzyme‐linked immunosorbent assay (ELISA), immunoradiometric assay (IRMA) and quantitative reverse transcription‐polymerase chain reaction (RT‐PCR). TNF‐α or IL‐1β induced both G‐CSF and PTHrP production in the conditioned medium. TNF‐α synergized with IL‐1β to significantly increase G‐CSF production. In addition, TNF‐α and IL‐1β strongly induced G‐CSF mRNA with peaks at 2 and 6 h respectively. Although PTHrP production was also strongly induced by TNF‐α PTHrP mRNA expression was more strongly induced by PMA than by TNF‐α. Thus, TNF‐α and IL‐1β could be common factors that individually and synergistically regulate G‐CSF and PTHrP production in OKa‐C‐1 cells. Moreover, G‐CSF and PTHrP production could be not only transcriptionally, but also posttranscriptionally regulated by other factors.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…[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.…”

mentioning

confidence: 99%

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

Vassilatou¹,

Fisfis²,

Morphopoulos³

et al. 2006

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thyroid tumors producing colony-stimulating factors associated with neutrophilia and/or eosinophilia are very rare and almost all of them concern anaplastic thyroid cancer. Only one case of papillary thyroid carcinoma associated with neutrophilia and one case of medullary thyroid carcinoma associated with eosinophilia have been reported. In this report a 72-year old male patient with metastatic papillary thyroid carcinoma associated with neutrophilia and eosinophilia is described. While investigating the cause of neutrophilia and eosinophilia, a blind bone marrow biopsy of the posterior iliac crest was performed, which showed infiltration by papillary thyroid carcinoma. High blood levels of granulocyte-macrophage colony-stimulating factor (GM-csF) were found using an enzyme-linked immunosorbent assay. As other causes of neutrophilia and eosinophilia were excluded, we assumed that these were paraneoplastic manifestations induced by GM-csF produced by the thyroid tumor. the disease progressed rapidly, despite appropriate treatment which included thyroidectomy and postoperative radioactive 131 I administration. the patient died 11 months after diagnosis because of extensive lung metastasis. Neutrophilia and eosinophilia were stable findings, while serum thyroglobulin levels remained elevated throughout the follow-up period. to our knowledge, this is the first report of a patient with metastatic papillary thyroid carcinoma in whom with neutrophilia and eosinophilia associated with high circulating levels of GM-csF were detected.

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Primary squamous cell carcinoma of the thyroid associated with marked leukocytosis and hypercalcemia

Cited by 83 publications

References 21 publications

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

Evidence that tumor necrosis factor plays a pathogenetic role in the paraneoplastic syndromes of cachexia, hypercalcemia, and leukocytosis in a human tumor in nude mice.

Regulation of Granulocyte Colony‐stimulating Factor and Parathyroid Hormonerelated Protein Production in Lung Carcinoma Cell Line OKa‐C‐1

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

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