Cytomorphological changes induced by intraperitoneal chemotherapy present important diagnostic pitfalls in peritoneal fluid cytology

Abstract

Intraperitoneal chemotherapy (IP ChT) is an emerging modality in the treatment of advanced gastric adenocarcinoma with peritoneal disease. Cytological evaluation of peritoneal fluid specimens from patients undergoing IP ChT is important in clinical management. However, direct intraperitoneal exposure to chemotherapeutic agents induces cytomorphological changes in benign constituents of peritoneal fluid, presenting particular challenges to accurate cytological interpretation. These morphological changes have not been well characterised in the literature. We systematically reviewed the cytomorphological features in immunocytochemically-confirmed positive and negative IP ChT peritoneal fluid samples to elucidate the degree of morphological overlap between malignant and reactive cells. We reviewed 39 peritoneal fluid samples of patients treated with IP ChT, and scored specific cytomorphological parameters of both benign and malignant cells with the aid of relevant immunocytochemical interrogation. The present findings show a significant degree of morphological overlap between reactive and malignant cells. Abnormal, "exploding" mitotic figures, nuclear membrane irregularities, multi-nucleation and cytoplasmic vacuolation were commonly observed in negative fluid specimens. The most helpful feature that favoured malignant cells was the increased nuclear-to-cytoplasmic ratio. A background inflammatory milieu of eosinophils and/or neutrophils was seen in 45-58% of post IP ChT peritoneal fluid specimens. The presence of pseudoparakeratotic cells, a novel observation in post IP ChT fluid specimens is also described. The extent of reactive cytomorphological anomalies arising from treatment with IP ChT poses unique diagnostic challenges and may prompt a malignant or 'atypical' diagnosis in benign reactive samples.