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Eosinophilia in a patient with lung adenocarcinoma--a case study.

Introduction

The eosinophil is a type of granulocyte and usually accounts for a very small proportion of total white cell count in peripheral blood. In our laboratory, an absolute eosinophil count of greater than 2.0 x [10.sup.9]/L is defined as marked eosinophilia. Eosinophilia, particularly marked eosinophilia, is a phenomenon commonly associated with allergy, parasitic infestations and drug hypersensitivities, but rarely linked to pre-existing solid tumors. We present here a case of a patient diagnosed with lung adenocarcinoma who then developed marked eosinophilia.

Case report

In July 2010, Mrs H, an 86 year old female, had her routine check-up performed at a rest home and blood samples were also taken. The full blood count analysis revealed remarkable abnormalities, including a haemoglobin (Hb) of 65 g/L (reference range: 115-155 g/L), mean cell volume (MCV) of 115 fl (reference range: 81-98 fl), platelet count of 48 x [10.sup.9]/L (reference range: 150-430 x [10.sup.9]/L) and a total white cell count of 61.3 x [10.sup.9]/L (reference range: 4.0-11.0 x [10.sup.9]/L). The DIFF scattergram from the XE2100 analyser contained a large grey-out area where the population of eosinophils normally locates (Figure 1). The analyser stated that 93% of the white cells were eosinophils. A blood film was then made to perform a manual white cell differential and examine cellular morphology. Sixty-nine percent of the white cells were identified as eosinophils, giving an absolute eosinophil count of 42.3 x [10.sup.9]/L. As shown in Figure 2, a proportion of the eosinophils appeared hypogranular. There was a left shift of neutrophils which also had features of toxic change. Moreover, occasional metamyelocytes and nucleated red blood cells were also noted.

The patient presented in the Emergency Department four hours later and similar full blood count results were obtained, where eosinophils accounted for 46% of the total white cell count. It was also found that the patient had an elevated Troponin T result and deteriorating renal function. The blood film was then reviewed by a haematologist who commented that it was consistent with secondary eosinophilia and leukamoid reaction, whilst bone marrow infiltration might also be involved. After her admission into the ward, she was transfused with two units of red cells and given prednisolone.

Further research on the patient revealed that Mrs H had pernicious anaemia since the age of 30. Since late 2007, the patient had developed mild macrocytic anaemia with a borderline low platelet count. In early 2009, she was diagnosed with malignant neoplasm of the lung, specifically adenocarcinoma of her right lung, using bronchoscopy and treated with radiotherapy. Three months later, Mrs H developed an episode of stroke. During her hospital admission, secondary neoplasm of lymph nodes, bone and bone marrow, mainly in the left pelvis, was confirmed which was then followed by another course of radiotherapy. Over the following years, she had several top-up transfusions and developed moderate thrombocytopenia of 80-100 x [10.sup.9]/L. Until the presentation of this event, an elevated white cell count (22.7-36.3 x [10.sup.9]/L) and eosinophilia ranging from 14% to 36% were frequent findings in her blood count.

Discussion

Eosinophilia in peripheral blood is often seen in individuals with allergy, parasitic infection, eosinophilic leukaemia and hypereosinophilic syndrome (1-4). The persistence of eosinophilia for an extended period of time can cause damage to various body tissues, mainly due to release of the contents of cytoplasmic granules in eosinophils (4). As a result, some eosinophils may appear degranulated or even agranular in the blood film (5). However, the occurrence of eosinophilia in people with solid tumors is low (3).

Several studies suggest that a number of cytokines are involved in the development of blood hypereosinophilia in cancer patients, particularly interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (1-3,6,7). Both cytokines play an important role in the production, activation and survival of eosinophils in the bone marrow and peripheral blood, as well as the enhancement of cellular functions of eosinophils in peripheral circulation (6,7).

GM-CSF is a growth factor that stimulates the development of myeloid cells, or myelopoiesis, via its receptors, and is synthesized mainly by stromal cells in the bone marrow (8). As an alternative source of GM-CSF in some lung cancer patients, its secretion by tumor cells has also been detected (1, 2, 8). Subsequently, proliferation of white cells is stimulated by exogenous GM-CSF resulting in leukocytosis as well as eosinophilia (1,7). IL-5, a cytokine normally produced by T cells, acts specifically on eosinophilic cell lineage allowing its activation (3,7). Additionally, the presence of IL-5 enhances cytotoxic function of the eosinophils against tumor cells in cancer patient (3).

Three major factors are thought to be responsible for the development of eosinophilia in patients with known cancers with or without metastasis (3). Locally produced active cytokines by tumor cells have direct effects on eosinophils and their functions (1.3). Tumor necrosis, as a result of treatment for cancers, such as radiotherapy, can lead to eosinophilia (3). It is usually a poor prognosis indicating possible persistence of tumor after treatment (9). Metastasis from the primary tumor, especially into bone marrow, results in bone marrow stimulation mediated by various cytokines and thus, eosinophilia in the peripheral circulation (3). For our patient, all theories above could be accountable.

Bone marrow aspirate is of limited use for differentiating between eosinophilia due to chronic eosinophilic leukaemia and paraneoplastic syndrome, relating to the underlying malignancy, since the hypercellular feature is common to both conditions. However, a measurement of GM-CSF level by immunoassay in pleural fluid in patients with lung cancer is valuable (1). Intracellular IL-5 in tumor cells determined by immunohistochemistry may also be used as a supplementary test (3). On the other hand, a chromosomal abnormality or molecular mutation is often one of the major findings in cases of chronic eosinophilic leukaemia (4). Unfortunately, our patient passed away two days after admission and no further analysis was carried out.

Conclusion

Besides the common eosinophilia occurring during allergic reactions and parasitic manifestations, it is likely that some patients with solid tumors will develop eosinophilia as one of the paraneoplastic syndromes, which is mediated by the actions of cytokines, especially when treatment-related tumor necrosis and/or metastasis into bone marrow have also been confirmed.

Author information

Jun (Rebecca) Lu, GCertScTech BMLSc MNZIMLS, Medical Laboratory Scientist

Craig Rodgers, MNZIMLS, Technical Manager and Medical Laboratory Scientist

Automation Department, Southern Community Laboratories, Southland Hospital, Invercargill.

Corresponding author

Jun (Rebecca) Lu, Automation Department, Southern Community Laboratories, Southland Hospital, PO Box 828, Invercargill.

Email: rebecca.lu@southerndhb.govt.nz

References

(1.) Sawyers CL, Golde DW, Quan S, Nimer SD. Production of granulocyte-macrophage colony-stimulating factor in two patients with lung cancer, leukocytosis, and eosinophilia. Cancer 1992; 69: 1342-1346.

(2.) El-Osta H, El-Haddad P, Nabbout N. Lung carcinoma associated with excessive eosinophilia. J Clin Oncol 2008; 26: 3456-3457.

(3.) Pandit R, Scholnik A, Wulfekuhler L, Dimitrov N. Non-small-cell lung cancer associated with excessive eosinophilia and secretion of interleukin-5 as a paraneoplastic syndrome. Am J Hematol 2007; 82: 234-237.

(4.) Hoffbrand AV, Moss PAH. Essential Haematology. 6th ed. Wiley-Blackwell, UK, 2011.

(5.) Bain BJ. Blood Cells: A Practical Guide. 4th ed. Blackwell Publishing, Australia, 2006.

(6.) Fridlender ZG, Simon HU, Shalit M. Metastatic carcinoma presenting with concomitant eosinophilia and thromboembolism. Am J Med Sci 2003; 326: 98-101.

(7.) Sun Q, Jones K, McClure B, Cambareri B, Zacharakis B, Iversen PO, et al. Simultaneous antagonism of interleukin-5, granulocyte-macrophage colony-stimulating factor, and interleukin-3 stimulation of human eosinophils by targeting the common cytokine binding site of their receptors. Blood 1999; 94: 1943-1951.

(8.) Watanabe M, Ono K, Ozeki Y, Tanaka S, Aida S, Okuno Y. Production of granulocyte-macrophage colony-stimulating factor in a patient with metastatic chest wall large cell carcinoma. Jpn J Clin Oncol 1998; 28: 559-562.

(9.) Lowe D, Jorizzo J, Hutt MS. Tumour-associated eosinophilia: a review. J Clin Pathol 1981; 34: 1343-1348.
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Author:Lu, Jun "Rebecca"; Rodgers, Craig
Publication:New Zealand Journal of Medical Laboratory Science
Date:Aug 1, 2013
Words:1327
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