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Journal of Clinical Oncology, Vol 26, No 20 (July 10), 2008: pp. 3456-3457 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.8899
Lung Carcinoma Associated With Excessive EosinophiliaUniversity of Kansas School of Medicine Wichita, Wichita, Kansas A 53-year-old male was admitted with abdominal pain, nausea, and vomiting. He described an intermittent moderate right lower-quadrant pain that started two weeks earlier and had progressed. Other associated symptoms were increased dyspnea, anorexia, and weight loss. Past medical history was positive for tuberculosis exposure and long-standing tobaccoism. Physical examination revealed a male in moderate acute distress, tachycardic and tachypneic, but without fever or hypoxemia. Abdominal palpation elucidated mild diffuse tenderness with no guarding. The rest of his physical examination was unimpressive. Basic lab findings revealed WBC count of 52,000/µL with 28% eosinophils (Fig 1). Ova and parasites were negative in the stools. Immunoglobulin E level was normal in blood. The rest of the labs were normal. Chest x-ray demonstrated a right hilar mass. Computed tomography scan of the abdomen and pelvis showed a 7.4 x 5.7 cm nonenhancing right adrenal mass that was intermediate in attenuation (Fig 2, white cross). He was started on hydration and symptomatic treatment resulting in clinical improvement. Concerns about malignancy prompted for further work-up. Computed tomography scan of the chest was obtained and showed large right hilar mass and multiple small nodules bilaterally consistent with metastasis (Fig 3). Magnetic resonance imaging scan of the brain demonstrated single metastatic lesion in the parietal lobe. A biopsy of the adrenal mass was performed without complications. The pathologic diagnosis was large-cell poorly differentiated lung carcinoma. The neoplastic cells were strongly positive for keratin, and the nuclei were positive for thyroid transcription factor. Stains for S100 protein, synaptophysin, and melan A were negative. Additionally, to rule out leukemic process, bone marrow biopsy was performed and showed no evidence of leukemia, affirming the reactive nature of the eosinophilia. Two weeks later, the patient was started on palliative chemotherapy and brain radiotherapy. He was readmitted 4 weeks later for alteration in mental status and increase in shortness of breath. His physical examination revealed new axillary and cervical lymph nodes. The peripheral blood leukocyte count was 112,000/µL; 48% were mature eosinophils. Prognosis was discussed with the family, and the patient was switched to comfort care. He succumbed few days after.
The presence of hypereosinophilia without evidence of an allergic reaction, parasitic infestation, or leukemic process on the bone marrow supports the paraneoplastic nature of the hypereosinophilia in this patient. Peripheral blood eosinophilia occurs in several medical conditions such as allergic disease, parasitic infection, certain forms of vasculitis, and medications, as well as in leukemia and lymphoma.1-3 However, eosinophilia in solid malignancies is rarely reported.4 It has been described in many kinds of solid tumors including thyroid,11 genitourinary,12 gastrointestinal,13 hepatocellular,14 breast,15 and lung carcinoma.2,8 In lung malignancies, it has been described in all types of cancer including small-cell,1 adenocarcinoma,16 and squamous cell.9 However, it is rarely reported in large-cell carcinoma.4,5,17 The pathogenesis of this phenomenon is controversial. Numerous explanations have been postulated. Bone marrow stimulation via circulatory factors secreted by the tumor itself is the most acknowledged and accepted theory.4-10 Interleukin-5, GM-CSF, and G-CSF are the most implicated factors studied. Other involved factors are still possible. In our patient, the hypereosinophilia along with the aggressive course of the disease might all be related to the increased level of certain immunomodulator and growth factor, although these cytokines had never been measured. Finally, this study as well as previous ones supports that eosinophilia in the context of malignancy generally reflect its aggressiveness and very poor prognosis.5,10,18-20 In fact, this patient already presented with metastatic disease before any treatment. Despite chemotherapy, his clinical course was marked by rapid progression and fatal outcome. Rare exceptions to this rule, where eosinophilia is associated with good prognosis or is not correlated with the prognosis, are reported in the literature.13,15 AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Niamut SM, de Vries PA, van Putten JW, et al: Eosinophilia caused by solid malignancy. Ned Tijdschr Geneeskd 148:1883-1886, 2004[Medline] 2. Fletcher S, Abdalla S, Edwards M, et al:. Case 32: Eosinophilia—Reactive or neoplastic? Leuk Lymphoma 48:174-176, 2007[CrossRef][Medline] 3. Matsunaga T, Sato T, Iyama S, et al: Peripheral T-cell lymphoma presenting with eosinophilia due to interleukin-5 produced by lymphoma cells [in Japanese]. Rinsho Ketsueki 47:1457-1462, 2006[Medline] 4. Pandit R, Scholnik A, Wulfekuhler L, et al: Non–small-cell lung cancer associated with excessive eosinophilia and secretion of interleukin-5 as a paraneoplastic syndrome. Am J Hematol 82:234-237, 2007[CrossRef][Medline] 5. Watanabe M, Ono K, Ozeki Y, et al: Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large-cell carcinoma. Jpn J Clin Oncol 28:559-562, 1998 6. Fridlender ZG, Simon HU, Shalit M: Metastatic carcinoma presenting with concomitant eosinophilia and thromboembolism. Am J Med Sci 326:98-101, 2003[CrossRef][Medline] 7. Nakada T, Sato H, Inoue F, et al: The production of colony-stimulating factors by thyroid carcinoma is associated with marked neutrophilia and eosinophilia. Intern Med 35:815-820, 1996[CrossRef][Medline] 8. Sawyers CL, Golde DW, Quan S, et al: Production of granulocyte-macrophage colony-stimulating factor in two patients with lung cancer, leukocytosis, and eosinophilia. Cancer 69:1342-1346, 1992[CrossRef][Medline] 9. Matsumoto S, Tamai T, Yanagisawa K, et al: Lung cancer with eosinophilia in the peripheral blood and the pleural fluid. Intern Med 31:525-529, 1992[CrossRef][Medline] 10. Stefanini M, Claustro JC, Motos RA, et al: Blood and bone marrow eosinophilia in malignant tumors: Role and nature of blood and tissue eosinophil colony-stimulating factor(s) in two patients. Cancer 68:543-548, 1991[Medline] 11. Vassilatou E, Fisfis M, Morphopoulos G, et al: Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating factor is associated with neutrophilia and eosinophilia. Hormones 5:303-309, 2006[Medline] 12. Dalal BI, Das KC, Dutta TK, et al: Local and systemic eosinophilia in patients with carcinoma of the uterine cervix undergoing radiation therapy: Correlation with radiation response. J Clin Oncol 4:18-21, 1992[Medline] 13. Iwasaki K, Torisu M, Fujimura I: Malignant tumor and eosinophils: Prognostic significance in gastric cancer. Cancer 58:1321-1327, 1986[CrossRef][Medline] 14. Yuen BH, Reyes CV, Rawal PA, et al: Severe eosinophilia and hepatocellular carcinoma: An unusual association. Diagn Cytopathol 13:151-154, 1995[CrossRef][Medline] 15. Sbalzarini G, Mercantini F, Pandolfi C, et al: Prognostic significance of hypereosinophilia in surgically treated breast carcinoma: Our experience. Minerva Med 82:807-809, 1991[Medline] 16. Henry DW, Rosenthal A, McCarty DJ: Adenocarcinoma of the lung associated with eosinophilia and hidebound skin. J Rheumatol 21:972-973, 1994[Medline] 17. Kodama T, Takada K, Kameya T, et al: Large cell carcinoma of the lung associated with marked eosinophilia: A case report. Cancer 54:2313-2317, 1984[CrossRef][Medline] 18. Teoh SC, Siow WY, Tan HT: Severe eosinophilia in disseminated gastric carcinoma. Singapore Med J 41:232-234, 2000[Medline] 19. Chang WC, Liaw CC, Wang PN, et al: Tumor-associated hypereosinophilia: Report of four cases. Changgeng Yi Xue Za Zhi 19:66-70, 1996[Medline] 20. Reddy SS, Hyland RH, Alison RE, et al: Tumor-associated peripheral eosinophilia: Two unusual cases. J Clin Oncol 2:1165-1169, 1984[Abstract]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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