Madeddu Clelia, Sanna Elisabetta, Nemolato Sonia, Mulas Olga, Oppi Sara, Scartozzi Mario, La Nasa Giorgio, Maccio Antonio
Department of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, Italy.
Department of Gynecologic Oncology, A. Businco Hospital, ARNAS G. Brotzu, 09100 Cagliari, Italy.
Diagnostics (Basel). 2022 Aug 7;12(8):1910. doi: 10.3390/diagnostics12081910.
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.
肿瘤相关性白细胞增多症与宫颈癌的不良预后相关。类白血病反应（即白细胞计数>40,000/μL）在存在分泌细胞因子的肿瘤（CST）且无肿瘤性骨髓浸润的情况下发生时被定义为副肿瘤性（PLR）。表现为PLR的宫颈癌代表一种特殊的实体，其特征是行为迅速进展，通常与放化疗耐药相关。本文旨在综述关于PLR的发病机制及其在宫颈癌中的预后作用的文献。此外，本文报告了一例伴有PLR且化疗耐药的晚期宫颈癌患者的典型病例。该患者接受了高复杂性的姑息性细胞减灭术，PLR暂时消退。肿瘤样本G-CSF和IL-6染色呈阳性，因此表明存在CST。值得注意的是，肿瘤基因组分析显示存在PI3CKA突变。因此，在影像学证据显示疾病迅速进展复发并伴有PLR再次出现时，我们开始使用选择性PIK3抑制剂alpesilib联合JAK1-2抑制剂芦可替尼进行靶向治疗。我们实现了症状缓解和白细胞增多症的减轻；然而，严重的副作用使治疗不得不暂停。总之，由于文献中很少报道针对伴有PLR的癌症的治疗策略，我们的研究可能有助于扩大我们对该主题的理解，并为进一步研究提供基础。
