Excessive Leukocytosis Leading to a Diagnosis of Aggressive Thyroid Anaplastic Carcinoma: A Case Report and Relevant Review

Abstract

Introduction: Leukocytosis and particularly neutrophilia are usually caused by acute infection, inflammation, and myeloproliferative neoplasms. However, leukocytosis can also occur in patients with malignancy either due to bone marrow metastases or in the context of a paraneoplastic syndrome. Case Presentation: An 86-year-old female was admitted to our hospital due to marked leukocytosis (white blood cells [WBC] > 40,000/μL), neutrophilia, and monocytosis. She was afebrile and reported hoarseness and mild difficulty swallowing. Upon physical examination, lung auscultation revealed inspiratory wheezing and a non-tender mass was observed in the anterior midline of the neck. Blasts and immature WBC were not found, and polymerase chain reaction for the detection of BCR/ABL gene was negative. A mass (5.4 cm in diameter) of abnormal parenchymal composition with calcifications occupying the right lobe, was seen on thyroid ultrasound. Cytology, after fine-needle aspiration, showed an anaplastic thyroid carcinoma (ATC). The cervical and chest computed tomography scan revealed a low-density lesion with calcifications that shifts and presses the trachea and multiple lung nodular lesions bilaterally. Since the case was inoperable and the airway was severely obstructed, a DUMON stent was placed. Biopsy of specimens from the trachea lesion revealed a tumor with significant atypical cells and focal squamoid features. The patient's WBC increased to 72,470/μL. Additionally, interleukin-6 (IL-6) was markedly elevated (20.2 pg/mL). The patient passed away due to respiratory arrest 55 days after her initial admission. Discussion: Excessive leukocytosis in a patient, having excluded infectious disease and myelodysplastic syndrome, could represent a manifestation of a paraneoplastic syndrome due to various cytokines secretion from the tumor. In our case, ATC synthesized and secreted IL-6, which seems to be the cause of severe leukocytosis.

Be(a)ware of Leukocytosis in Papillary Thyroid Cancer

“…yroid malignancies have also been associated with paraneoplastic leukocytosis. Two cases of squamous cell carcinoma [7,8] and seventeen cases of anaplastic tumor have been reported [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Both cases of squamous cell carcinoma were related to marked leukocytosis and hypercalcemia.…”

“…Elevated G-CSF levels were detected in anaplastic thyroid cancer cases. Only a few case reports evaluated IL-6 levels as either elevated or within the normal range [10][11][12]23].…”

Three Cases of Anaplastic Thyroid Carcinoma Transformation and Leukocytosis during Lenvatinib Treatment

“…However, there are very few reports where leukocytosis is a primary marker in an ATC diagnosis. Since 1992, 17 cases diagnosed as ATC with leukocytosis have been reported worldwide, of which 13 cases have been in Japan [ 3 ]. It is significant that three patients in the same facility were diagnosed within 3 months for this disease.…”

“…They initially saw good results and shrinkage of their tumors from the lenvatinib use, but they developed excessive leukocytosis and rare anaplastic thyroid cancer. There have been other cases where patients who were later diagnosed with anaplastic thyroid cancer (ATC) originally presented with excessive leukocytosis and high levels of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) [ 3 ]. Very rarely, leukocyte hyperplasia and rapid disease progression have been reported as aggressive cancers in the lung or stomach [ 4 , 5 ].…”

Research progress of immunotherapy against anaplastic thyroid cancer

“…The transcription factor CREB3L1 activates the extracellular matrix signaling pathway, maintains the fibroblast-like characteristics of ATC cells, reshapes the tumor interstitial microenvironment, and drives ATC malignant transformation ( 34 ). ATC is also linked to elevated levels of other cytokines, including IL-6, IL-1, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, CXCL8, and CXCR4 ( 35 , 36 ). One obvious characteristic of ATC is the high percentage of immunosuppressive cytokines ( 24 ).…”