Pathogenic and prognostic roles of paraneoplastic leukocytosis in cervical cancer: can genomic-based targeted therapies have a role? a literature review and an emblematic case report
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Authors
Madeddu, Clelia
Sanna, Elisabetta
Nemolato, Sonia
Mulas, Olga
Oppi, Sara
Scartozzi, Mario
Nasa, Giorgio La
Maccio, Antonio
Issue Date
2022-08-07
Type
Article
Language
en_US
Keywords
Cervical Cancer , Leukocytosis , Cytokine-Secerning Tumor , Interleukin-6 , Myeloid-Derived Suppressive Cells , Prognosis , Chemoresistance , Alpesilib , Ruxolitinib , Cytoreductive Surgery
Alternative Title
Abstract
Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/μL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research.
Description
Citation
Madeddu, C., Sanna, E., Nemolato, S., Mulas, O., Oppi, S., Scartozzi, M., La Nasa, G., & Maccio, A. (2022). Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report. Diagnostics (Basel, Switzerland), 12(8), 1910. https://doi.org/10.3390/diagnostics12081910
Publisher
Diagnostics (Basel, Switzerland)