Paraneoplastic leukemoid reactions induced by cytokine-secreting tumours

Abstract

<jats:p>Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour. The clinical presentation is widely variable, and therefore challenging. If the underlying malignancy is not clinically apparent, PLR could be mistaken for myeloproliferative neoplasms, altering the patient’s management. CSTs are highly aggressive tumours associated with a poor prognosis due to multiple mechanisms. Localising and treating the underlying malignancy is the mainstay of treatment. Both the treating clinician and the pathologist should keep a high level of suspicion for this entity in patients having unexplained leukocytosis. We herein discuss the underlying mechanisms, clinical presentation, pathological features, differential diagnosis and prognosis of this rare entity. An emphasis on the role of the pathologist is provided since the lack of knowledge on this entity can lead to dramatic effects on the patient, including unnecessary diagnostic testing and treatments.</jats:p>

Metastatic BRAF V600E-Mutated Adenocarcinoma of the Lung Presenting as Extreme Neutrophilia and Eosinophilia

“…Tumor-induced leukocytosis can be mistaken for infection or myeloproliferative neoplasms (MPN) if the underlying malignancy is not clinically evident [ 6 ]. Infection should initially be excluded since it is more common than PLR as a cause of secondary leukocytosis.…”

“…Other than myeloproliferative neoplasm (MPN), there are many other etiologies that can cause leukemoid reaction, including infections (e.g., clostridium difficile colitis, disseminated tuberculosis, severe shigellosis), malignancies (e.g., carcinomas, Hodgkin's lymphoma, melanoma, sarcoma), drugs (e.g., corticosteroids, minocycline, recombinant hematopoietic growth factors), intoxication (e.g., ethylene glycol), or severe hemorrhage or acute hemolysis [6]. This is the first reported case of a patient with BRAF V600E-mutated metastatic adenocarcinoma of the lung who presented with extreme neutrophilia and eosinophilia as a hematologic paraneoplastic syndrome and is being treated with dabrafenib and trametinib.…”

“…Other than myeloproliferative neoplasm (MPN), there are many other etiologies that can cause leukemoid reaction, including infections (e.g., clostridium difficile colitis, disseminated tuberculosis, severe shigellosis), malignancies (e.g., carcinomas, Hodgkin's lymphoma, melanoma, sarcoma), drugs (e.g., corticosteroids, minocycline, recombinant hematopoietic growth factors), intoxication (e.g., ethylene glycol), or severe hemorrhage or acute hemolysis [ 6 ].…”

Cross‐talk between tumors at anatomically distinct sites

“…A clinical example of this comes from paraneoplastic leukemoid reaction (PLR), which describes a variety of hematological clinical disorders due to a nonhematolymphoid tumor. PLR has been reported in patients with a variety of cancers, including lung cancers, melanoma, mesothelioma, head and neck cancer, and cancers of other origins [2]. The most commonly secreted cytokine by these tumors include granulocyte colony‐stimulating factor (G‐CSF), granulocyte–macrophage colony‐stimulating factor (GM‐CSF), IL‐1, IL‐6, and TNF‐α.…”

Leukemoid Reaction in a Case of Chronic Cholecystitis With Focal Mild Acute Inflammation

“…Leukemoid reaction is a condition of marked increase of the white blood cell (WBC) count in the peripheral blood with the different cut point of more than 30 × 10 9 /L, 1 40 × 10 9 /L, 2 or 50 × 10 9 /L in most authorities. [3][4][5] And the main WBCs involved are mature neutrophil possibly with the left shift.…”