Inflammatory malignant fibrous histiocytoma (IMFH) associated with leukemoid reaction (LR)/leukocytosis is a rare entity. In this paper, we search PubMed for all known cases of IMFH associated with LR/leukocytosis in an attempt to draw conclusions about this variant’s response to treatments and its pathophysiology. Medline electronic database was searched using key words such as malignant fibrous histiocytoma, leukemoid reaction, and leukocytosis. A total of 16 patients were found, twelve males (75%) and 4 female (25%), with a mean age of 62.6 years, ranging from 47 to 77. The mean survival was 770 days, ranging from 14 to 6570 days. Four patients were alive at last follow-up: 6570 days, 1095 days, 335 days, and 180 days, respectively. Of the 12 patients that expired, death occurred approximately 92 days after the onset of LR or leukocytosis, ranging from 3 to 334 days. We conclude that IMFH associated with LR/leukocytosis does not completely respond to chemoradiation. Overproduction of growth factors and cytokines by IMFH cells and their interactions with the inflammatory infiltrate seem to promote immunological effector cell’s dysfunction and substantiate the development and growth of this neoplasm. A clear understanding of these molecular pathways is crucial in order to identify targets for potential therapy. 1. Introduction Inflammatory malignant fibrous histiocytoma (IMFH), also known as undifferentiated pleomorphic sarcoma (UPS) inflammatory variant, was initially identified as a separate category by Kyriakos and Kempson in 1976 [1]. Its name is derived from its distinct histological pattern; an intense inflammatory infiltrate that may be composed of neutrophils, eosinophils, and/or lymphocytes without a recognized source of infection. These tumors are usually bulky, and their clinical course is characterized by multiple local recurrences, metastasis, and ultimately death. Due to its mesenchymal origins, this neoplasm can virtually affect any part of the body; however, they are most commonly encountered in the retroperitoneal cavity. Patients typically present with fever and other constitutional symptoms mimicking an infectious process, and/or a rapidly growing painful mass. In cases of retroperitoneal IMFH, patients can also present with additional signs/symptoms of a space-occupying lesion [2–6]. Conventionally, leukemoid reaction (LR) is defined as a secondary leukocytosis with a white blood cell count (WBC) that is frequently above 50？K/mm3 resulting in a severe left shift with the presence of immature myeloid cells in the peripheral blood,
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