Paraneoplastik Lökositozis
Özet
Paraneoplastik lökomoid reaksiyon (PLR), hematolojik bir malignite veya kemik iliği infiltrasyonu olmaksızın, katı tümörlerin sitokin salgılaması sonucu beyaz kan hücresi sayısının 40.000/µL'nin üzerine çıkmasıyla karakterize, nadir ve agresif bir klinik tablodur. En sık akciğer kanserinde görülmekle birlikte, çeşitli organ karsinomlarında da bildirilmiştir. Mekanizmasında genellikle tümör hücreleri tarafından doğrudan granülosit koloni uyarıcı faktör (G-CSF) salgılanması rol oynar. Bu durum, reaktif granülositoza yol açarak klinik sunumda ateş ve lökositoz nedeniyle enfeksiyon veya kronik miyeloid lösemi gibi miyeloproliferatif neoplazmlarla kolayca karıştırılabilir; bu da gereksiz tanısal prosedürlere neden olur. Ayırıcı tanıda ekzojen büyüme faktörü kullanımı öncelikle dışlanmalı, morfolojik incelemeler ve BCR/ABL1 gibi moleküler testlerden yararlanılmalıdır. PLR, kan viskozitesini artıran hiperlökositoza ve tümör lizis sendromuna yol açabileceğinden acil müdahale gerektirebilir. Tedavinin temel dayanağı cerrahi, kemoterapi veya radyoterapi ile altta yatan malignitenin ortadan kaldırılmasıdır. Ancak, PLR gelişen hastalar genellikle yüksek tümör yükü, hızlı tümör büyümesi ve bağışıklık baskılanması nedeniyle kötü bir prognoza sahip olup, olguların büyük kısmı tanıdan sonraki ilk üç ay içinde kaybedilmektedir.
Paraneoplastic leukemoid reaction (PLR) is a rare and aggressive clinical condition characterized by a white blood cell count exceeding 40,000/µL, triggered by cytokine-secreting solid tumors in the absence of hematologic malignancies or bone marrow infiltration. Although most commonly associated with lung cancer, it has been reported in various carcinomas. The underlying mechanism predominantly involves the direct secretion of granulocyte colony-stimulating factor (G-CSF) by tumor cells. This causes reactive granulocytosis, which can easily be misidentified as an infection or myeloproliferative neoplasms like chronic myeloid leukemia due to symptoms like fever and leukocytosis, leading to unnecessary diagnostic tests. In differential diagnosis, the use of exogenous growth factors must be excluded, and morphological evaluations alongside molecular tests such as BCR/ABL1 should be utilized. PLR can result in hyperleukocytosis and tumor lysis syndrome, which elevate blood viscosity and constitute a medical emergency. The mainstay of treatment is addressing the underlying malignancy through surgery, chemotherapy, or radiotherapy. However, patients developing PLR generally carry a poor prognosis and shorter survival due to high tumor burden, rapid growth, and immunosuppression, with the majority passing away within three months of presentation.
Referanslar
Shijubo N, Inoue Y, Hirasawa M, et al. Granulocyte colony-stimulating factor-producing large cell undifferentiated carcinoma of the lung. Intern Med 1992;31:277–80.
Kasuga I, Makino S, Kiyokawa H, et al. Tumor-Related leukocytosis is linked with poor prognosis in patients with lung carcinoma. Cancer 2001;92:2399–405.
Sakka V, Tsiodras S, Giamarellos-Bourboulis EJ, et al. An update on the etiology and diagnostic evaluation of a leukemoid reaction. Eur J Intern Med 2006;17:394–8.
Gouveia E, Sousa M, Passos MJ, et al. Paraneoplastic leukemoid reaction in a patient with BRAF V600E-mutated metastatic malignant melanoma. Case Reports 2015;2015:bcr2014208645.
Asano S, Urabe A, Okabe T, et al. Demonstration of granulopoietic factor(s) in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue. Blood 1977;49:845–52.
Jain P, Roop Rai R, Jha A. Hepatocellular carcinoma manifesting as cavitary lung metastases and leukemoid reaction. Journal of gastrointestinal and liver diseases : JGLD 2008;17:355–6.
Aita K, Seki K. Carcinosarcoma of the liver producing granulocyte-colony stimulating factor. Pathol Int 2006;56:413–9.
Nagata H, Komatsu S, Takaki W, et al. Granulocyte colony-stimulating factor-producing hepatocellular carcinoma with abrupt changes. World J Clin Oncol 2016;7:380–6.
Furihata M, Sonobe H, Ohtsuki Y, et al. An immunohistochemical study on a case of granulocyte-colony stimulating factor-producing gall-bladder carcinoma. Pathol Int 1999;49:1010–3.
Mori H, Shibuya T, Osada T, et al. Response to chemotherapy in a case of gastric adenocarcinoma producing granulocyte colony-stimulating factor. Med Sci Monit 2010;16:Cs119–23.
Tachibana M, Miyakawa A, Tazaki H, et al. Autocrine growth of transitional cell carcinoma of the bladder induced by granulocyte-colony stimulating factor. Cancer Res 1995;55:3438–43.
Murabe H, Akamizu T, Kubota A, et al. Anaplastic thyroid carcinoma with prominent cardiac metastasis, accompanied by a marked leukocytosis with a neutrophilia and high GM-CSF level in serum. Internal Medicine 1992;31:1107–11.
Fukuda S, Fujiwara Y, Mishima H, et al. Choroidal metastasis from granulocyte colony- stimulating factor-producing esophageal squamous cell carcinoma: a case report. Clinical Case Reports 2017;5:419–24.
Yamano T, Morii E, Ikeda J-I, et al. Granulocyte colony-stimulating factor production and rapid progression of gastric cancer after histological change in the tumor. Jpn J Clin Oncol 2007;37:793–6.
Kawaguchi M, Asada Y, Terada T, et al. Aggressive recurrence of gastric cancer as a granulocyte-colony-stimulating factor-producing tumor. Int J Clin Oncol 2010;15:191–5.
Kaneko N, Kawano S, Matsubara R, et al. Tongue squamous cell carcinoma producing both parathyroid hormone-related protein and granulocyte colony- stimulating factor: a case report and literature review. World J Surg Oncol 2016;14:161.
Suzumura K, Iimuro Y, Hirano T, et al. Granulocyte colony-stimulating Factor– Producing cholangiocellular carcinoma. Int Surg 2015;100:123–7.
Kojima K, Nakashima F, Boku A, et al. Clinicopathological study of involvement of granulocyte colony stimulating factor and granulocyte-macrophage colony stimulating factor in non-lymphohematopoietic malignant tumors accompanied by leukocytosis. Histol Histopathol 2002;17:1005–16.
Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor (1). N Engl J Med 1992;327:28–35.
Kitamura H, Kodama F, Odagiri S, et al. Granulocytosis associated with malignant neoplasms: a clinicopathologic study and demonstration of colony-stimulating activity in tumor extracts. Hum Pathol 1989;20:878–85.
Hoshimoto S, Hoshi N, Ozawa I, et al. Rapid progression of a granulocyte colony- stimulating factor-producing liver tumor metastasized from esophagogastric junction cancer: a case report and literature review. Oncol Lett 2018;15:6475–80.
Wilcox RA. Cancer-Associated myeloproliferation: old association, new therapeutic target. Mayo Clinic Proceedings 2010;85:656–63.
Qasrawi A, Tolentino A, Ghanimeh MA, et al. BRAF V600Q-mutated lung adenocarcinoma with duodenal metastasis and extreme leukocytosis. World J Clin Oncol 2017;8:360–5.
Granger JM, Kontoyiannis DP. Etiology and outcome of extreme leukocytosis in 758 nonhematologic cancer patients: a retrospective, single-institution study. Cancer 2009;115:3919–23.
Sreevatsa A, Babu SMC, Babu GK, et al. Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: case report and review of literature. J Cancer Res Ther 2015;11:669.
Jain R, Bansal D, Marwaha RK. Hyperleukocytosis: emergency management. Indian J Pediatr 2013;80:144–8.
Lammel V, Stoeckle C, Padberg B, et al. Hypereosinophilia driven by GM-CSF in large- cell carcinoma of the lung. Lung Cancer 2012;76:493–5.
Meyerson HJ, Farhi DC, Rosenthal NS. Transient increase in blasts mimicking acute leukemia and progressing myelodysplasia in patients receiving growth factor. Am J Clin Pathol 1998;109:675–81.
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 1992;69:1342–6.
Elliott MA, Tefferi A. Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management. Am J Hematol 2018;93:578–87.
Sasaki M, Tsuneyama K, Ishikawa A, et al. Intrahepatic cholangiocarcinoma in cirrhosis presents granulocyte and granulocyte-macrophage colony-stimulating factor. Hum Pathol 2003;34:1337–44.
