|Year : 2015 | Volume
| Issue : 3 | Page : 669
Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature
Aparna Sreevatsa, Suresh M. C. Babu, Govind K Babu, TM Suresh
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India
|Date of Web Publication||9-Oct-2015|
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Dr. M.H. Marigowda Road, Bangalore - 560 010, Karnataka
Source of Support: None, Conflict of Interest: None
Leukocytosis may be found in patients with lung cancer either at time of diagnosis or during the course of the disease. Though mild leukocytosis is common in lung cancer, hyperleukocytosis defined as total leukocyte count more than 100,000 is uncommon. We describe a 68-year-old chronic smoker who presented with osteolytic pelvic bone lesion and hyperleukocytosis, who on evaluation was found to have a primary lung cancer. Bone marrow aspiration and biopsy showed marked myeloid hyperplasia. Myeloid series comprised predominantly mature neutrophils and stab forms. Cytogenetic investigation showed a normal chromosome set (46, XY). Repeated cultures from blood, urine, and sputum were sterile. He was started on chemotherapy but had a progressive downhill course. In patient with lung cancer, leukocytosis can be due to infection, use of corticosteroid or hematopoetic growth factors, bone marrow involvement, or paraneoplastic manifestation. Paraneoplastic leukocytosis is associated with poor prognosis and aggressive disease.
Keywords: Hyperleukocytosis, lung cancer, paraneoplastic
|How to cite this article:|
Sreevatsa A, Babu SM, Babu GK, Suresh T M. Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature. J Can Res Ther 2015;11:669
|How to cite this URL:|
Sreevatsa A, Babu SM, Babu GK, Suresh T M. Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature. J Can Res Ther [serial online] 2015 [cited 2019 Nov 17];11:669. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/669/151865
| > Introduction|| |
Lung cancer is the most common cancer affecting men in India according to GLOBOCON 2012 data. Hematologic abnormalities including anemia, leukocytosis, thrombocytosis, and eosinophilia are frequently observed in lung cancer patients. Though mild leukocytosis is common in lung cancer, hyperleukocytosis defined as total leukocyte count more than 100,000 is uncommon, with only four cases reported in literature. ,, Hyperleukocytosis is associated with a dismal prognosis. We describe a patient who presented with osteolytic pelvic bone lesion and hyperleukocytosis, who on evaluation was found to have a primary lung cancer. He had an aggressive disease and downhill course unresponsive to therapy.
| > Case report|| |
A 60-year-old man, a chronic smoker, presented with pain and swelling in left groin of 4-months duration. He had no constitutional symptoms like fever, night sweats, or weight loss. He had not received corticosteroids or growth factors. His performance status was 2 eastern cooperative oncology group ( ECOG). Examination revealed mass in left iliac fossa extending to left upper thigh measuring 15 cm × 10 cm, firm in consistency, tender, and associated with restricted hip joint extension. Systemic examination was normal.
His hemoglobin was 8.8 gm, total leukocyte count (TLC) was 1.6 lakh with 90% band forms and neutrophils [Figure 1]. Platelet count was 307,000. Alkaline phosphatase was 645 U/dL. Magnetic resonance imaging (MRI) of pelvis and left thigh revealed osteolytic lesion arising from left superior pubic ramus and portion of left acetabulum with large soft tissue component both in extraperitoneal portion of pelvis and in the anteromedial aspect of upper thigh. Lesion involved lower aspect of rectus abdominis, left obturator internus, externus, and inferiorly adductor group of muscles at their origin [Figure 2]. Skeletal scintigraphy found no other evidence of osteolysis. Trucut biopsy of thigh swelling revealed poorly differentiated neoplasm composed of pleomorphic and round cells. On immunohistochemistry, neoplastic cells were diffusely positive for CK, CK7, and focally for epithelial membrane antigen (EMA). Cells were negative for HMB45, Melan A, H-caldesmon, desmin, TTF1, CDX2, CD20, prostate specific antigen (PSA), and CD34 and was suggestive of metastatic poorly differentiated carcinoma, primary in upper aerodigestive tract. Computed tomography of thorax showed a lesion in the right middle lobe of lung [Figure 3]. There were no mediastinal lymph nodes or adrenal metastases. Bone marrow aspiration and biopsy showed marked myeloid hyperplasia. Myeloid series comprised predominantly mature neutrophils and stab forms [Figure 4]. Cytogenetic investigation showed a normal chromosome set (46, XY). Polymerase chain reaction failed to demonstrate a breakpoint cluster region-abelson (BCR-ABL) fusion gene. Repeated cultures from blood, urine, and sputum were sterile.
|Figure 1: Peripheral smear showing Predominantly mature neutrophils and band forms|
Click here to view
|Figure 2: MRI Pelvis showing T1 hypointense and T2 STIR mixed signal intensity (iso to hypointens) lesion noted arising from superior pubic ramus and portion of left acetabulum with large soft tissue component both in extraperitoneal portion of pelvis and in the anteromedial aspect of upper thigh|
Click here to view
|Figure 3: Computed tomography of thorax showing lesion in the right middle lobe of lung|
Click here to view
|Figure 4: Bone marrow aspiration showing Myeloid hyperplasia predominantly mature neutrophils and stab forms|
Click here to view
During hospitalization for evaluation, patient developed features of raised intracranial pressure. MRI of brain showed multiple lesions in right frontal and right anterial temporal horn with perilesional edema [Figure 5].
|Figure 5: CT Brain showing Hyperintense lesions in Right frontal lobe with perilesional edema|
Click here to view
Patient received anti-edema measures, followed by cranial irradiation 10 fractions of 30 gy each. Chemotherapy was started with Paclitaxel (80 mg/m 2 ) and Carboplatin (AUC 2) every weekly. After first cycle of chemotherapy, TLC dropped to a nadir of 1,100 and recovered to 85,000 before the second cycle. Patient had a progressive downhill course with worsening performance status and chemotherapy was abandoned. His overall survival was 2 months.
| > Discussion|| |
Paraneoplastic syndromes are estimated to occur in 7-15% of all patients with cancer.  Lung cancer is the most common cancer to be associated with paraneoplastic syndromes. In a study of 227 patients with lung cancer, 15% had leukocytosis.  Nearly all patients had non-small cell lung cancer.
When a patient with cancer presents with an elevated leukocyte count, especially with a granulocytic predominance, bacterial infection has to be ruled out. Other iatrogenic causes like corticosteroid or hematopoetic growth factor administration should be considered. Chemotherapy with gemcitabine and cisplatin can cause leukocytosis with lymphocytic predominance.  Once bone marrow involvement and unrelated coexistent leukemia have been ruled out, paraneoplastic leukocytosis should be entertained. Our patient qualifies for paraneoplastic leukocytosis as he did not have fever, cultures did not grow any organism, bone marrow did not show marrow involvement by tumor or immature blasts, and BCR-ABL was negative.
Shalom et al.  reported two patients (a 61-year-old woman with poorly differentiated large cell carcinoma and a 43-year-old man with poorly differentiated squamous epithelial carcinoma) with extensive metastases with total leukocyte count exceeding 150,000 cells/μL with granulocyte fraction exceeding 90%. Both patients had poor response to chemotherapy and died 4 and 7 months after the initial diagnosis. Reisenberg et al.  described a 51-year-old woman with poorly differentiated adenocarcinoma lung with stage 4 disease with TLC of 140,000. The patient had extensive osteolysis in the acetabulum with infiltration of the iliopsoas muscle similar to the index patient. She died within 5 months of diagnosis. Kasuga et al.  described a 48-year-old woman with large cell lung cancer with stage 4 disease who had a TLC of 190,000 and died 8 months after diagnosis.
Paraneoplastic leukocytosis is due to overproduction of granulocyte-colony stimulating factor (G-CSF).  Granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-6 production of lung carcinomas has also been reported to be associated with leukocytosis. , Epithelial tumors can express various forms of the G-CSF receptor and that cell proliferation may occur after ligand binding.  Paraneoplastic production of growth factors by the tumor leads to permanent autocrine stimulation of these tumor cells and explains the high aggressiveness and the uncontrollable progression. Aggressiveness was also linked to metalloproteinase secretion by tumors, stimulated by GM-CSF.
A diagnosis of paraneoplastic hyperleukocytosis is important because it has an important prognostic value. Though there are a few case reports of patients achieving resolution of their malignancy-related leukocytosis with the initiation of chemotherapy, in majority of patients these abnormalities persist and these patients tend to have poor outcome. 
| > Conclusion|| |
Hyperleukocytosis can be a rare paraneoplastic manifestation of primary lung cancer. It is associated with aggressive course and poor response to therapy.
| > References|| |
Shalom G, Sion-Vardy N, Dudnik J, Ariad S. Leukemoid reaction in lung cancer patients. Isr Med Assoc J 2010;12:255-6.
Riesenberg H, Müller F, Görner M. Leukemoid reaction in a patient with adenocarcinoma of the lung: A case report. J Med Case Rep 2012;6:211.
Kasuga I, Makino S, Kiyokawa H, Katoh H, Ebihara Y, Ohyashiki K. Tumor-related leukocytosis is linked with poor prognosis in patients with lung carcinoma. Cancer 2001;92:2399-405.
Richardson GE, Johnson BE. Paraneoplastic syndromes in lung cancer. Curr Opin Oncol 1992;4:323-33.
Lissoni P, Fumagalli L, Brivio F, Rovelli F, Messina G, Di Fede G, et al
. Cancer chemotherapy-induced lymphocytosis: A revolutionary discovery in the medical oncology. J Biol Regul Homeost Agents 2006;20:29-35.
Asano S, Urabe A, Okabe T, Sato N, Kondo Y. Demonstration of granulopoietic factors in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue. Blood 1977;49:845-52.
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;69:1342-6.
Matsuguchi T, Okamura S, Kawasaki C, Shimoda K, Omori F, Hayashi S, et al
. Constitutive production of granulocyte colony-stimulating factor and interleukin-6 by a human lung cancer cell line, KSNY: Gene amplification and increased mRNA stability. Eur J Haematol 1991;47:128-33.
Berdel WE, Danhauser-Riedl S, Steinhauser G, Winton EF. Various human hematopoietic growth factors (interleukin-3, GM-CSF, G-CSF) stimulate clonal growth of nonhematopoietic tumor cells. Blood 1989;73:80-3.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]