Undifferentiated Epithelioid Sarcoma Presenting as a Fever of Unknown Origin

A Case Report

Nicholas Sajko; Shannon Murphy; Allen Tran


J Med Case Reports. 2019;13(24) 

In This Article


The presence of FUO and neoplastic-based fevers with bone or STSs, as was the case with our patient, is not extensively reported in literature. In a cohort of 195 patients with bone and STSs who were admitted for treatment, 58 (30%) developed a fever while in hospital. Neoplastic fever was determined to be the cause in only 11 (6%).[1] Due to the extensive number of other potential etiologies that could be responsible for FUO, the workup can be complex and extensive. An important part of this workup is obtaining a detailed history, as the major categories of classical FUO have distinct clinical hallmarks. Constitutional symptoms, anorexia, weight loss, fatigue, and malaise typify malignant/neoplastic etiologies of FUO. However, these vague symptoms need to be correlated to physical examination findings, laboratory studies, and diagnostic imaging, to make a definitive diagnosis. A retrospective review of 383 patients found that the mean time to diagnosis of a neoplastic cause of FUO after admission was 15.7 days.[7] This case, where extensive workup involved both in-patient and out-patient investigations lasting over 1 month, highlights the importance of a detailed history and repeated examinations when evaluating FUO. This patient initially had a history of transient left knee pain, which was previously investigated with only X-rays. When symptoms recurred, a focused physical examination of the area, as well as additional imaging studies, led to the diagnosis. Time to diagnosis may have been shortened should this history of knee pain been investigated earlier.

Investigation of FUO, guided by patient history and physical examination findings, should begin with a broad systematic approach to narrow the differential as efficiently as possible. Table 5 outlines a practical approach for the initial workup of FUO. Imaging techniques, such as fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, play an increasingly important role in the investigation of FUO without any diagnostic clues. One review found FDG-PET/CT contributed to determining the final causal diagnosis in FUO in 38–75% of cases.[8] In addition, a systematic review examining data from 16 trials found that PET/CT imaging was 90% sensitive and 89% specific for overall diagnostic accuracy in osseous and STSs.[9] However, this imaging modality was not utilized in this case. Whether or not its use would have led to an earlier diagnosis is something that could be considered given the above data.

Prognosis is variable in FUO, reflecting the multitude of potential etiologies.[5] Overall, 12–35% of patients die from FUO-related causes, with malignant etiologies having the highest 5-year mortality at 52–100%.[5] This sharply contrasts with the 5-year mortality rate of 3.2% in those patients who remain undiagnosed after an extensive evaluation. Spontaneous recovery from FUO can occur in 51–100% of patients.[5]

In the current era, limb sparing treatment procedures are often the preferred management option for STS. Along with surgical resection, adjuvant radiotherapy and chemotherapy can also be a key component to the management of STS. As was the case with our patient who had a grade 3 STS, most moderate to high-grade STSs receive adjuvant radiotherapy. The combination of local resection and radiotherapy has similar survival and recurrence rates as amputation, but with the added benefit of functional preservation.[10] However, the role for adjuvant chemotherapy is more controversial and is dependent on the histologic subtype and morphology of the tumor, as well as the presence of metastases.[10] Although our patient did develop metastatic disease, she had opted to pursue palliative care in lieu of further aggressive treatment.