Morphological effects of chemotherapy on ovarian carcinoma

Abstract

Aims: Traditionally, advanced stage ovarian carcinoma is treated by debulking surgery followed by chemotherapy. However, in some circumstances preoperative chemotherapy may be given before optimal surgical debulking. This study aims to describe the morphological features found in ovarian carcinoma after chemotherapy because these have not been detailed previously. Methods: Histological sections were examined from 18 cases of ovarian carcinoma that had been treated by preoperative chemotherapy. The morphology was compared with any pre-chemotherapy biopsies that had been performed. Tumours were classified as showing morphological features suggesting a good response to chemotherapy (n = 14) or as showing little or no response (n = 4). Serum CA125 values before and after chemotherapy were compared. In all cases, the mitotic activity index (MAI), volume percentage of epithelium (VPE), and mean nuclear area (MNA) of tumour cells were calculated. Results: The preoperative biopsies were all typical ovarian serous or endometrioid adenocarcinomas. Morphological features present in the group responding to chemotherapy included the presence of small groups or single tumour cells in a densely fibrotic stroma. Tumour cells were characterised by both nuclear and cytoplasmic alteration, making accurate tumour typing and grading impossible. Nuclear features included the presence of bizarre enlargement with hyperchromatism, irregularity of outline, and chromatin clumping or smudging. Cytoplasmic alterations included intense eosinophilia, vacuolation, or foam cell change. There were pronounced stromal changes of fibrosis, inflammation, collections of foamy histiocytes, cholesterol cleft formation, haemosiderin deposition, fat necrosis, and dystrophic calcification, including the presence of many free psammoma bodies. There was no correlation between morphological response and biochemical response, as determined by serum CA125 values. In all nine cases in which pre-chemotherapy and post-chemotherapy biopsies were available, the MNA increased post-chemotherapy (p = 0.007, paired Wilcoxon test) and in six of nine cases the MAI decreased (p = 0.093). Conclusions: Because preoperative chemotherapy is being used increasingly in the management of ovarian cancer, pathologists should be aware of the resultant morphological effects. Accurate tumour typing and grading is impossible. In some cases, it may be difficult to confirm the presence of residual tumour, making it imperative that pre-chemotherapy tissue biopsies are obtained. Definite confirmation of residual tumour may require the examination of multiple histological sections from areas showing pronounced stromal changes, sometimes with multiple levels and immunohistochemistry. In the absence of definite residual tumour, the report should state that the features are consistent with the prior presence of tumour.

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

“…Hematoxylin and eosin slides from the debulking surgery were retrieved from the pathology archives and the clinical and follow-up data were retrieved form medical records. Because as already known that chemotherapy can deeply affect tumor cell morphology and grading, the histologic subtype and grade of the tumor on the debulking specimen were not recorded for our study [4,5].…”

“…However, there is increasing awareness of the necessity to understand a tumor within the context of its surroundings, so called "tumor microenvironment". The stromal component of tumor usually constitutes a high percentage of tumor volume, especially in malignancies treated with neoadjuvant chemotherapy [4,5]. The tumor microenvironment is vital for tumor survival, growth, proliferation, metastasis, and even progression.…”

“…Residual tumor disease and tumor stage are the two most important factors to predict disease outcome in patients with EOC treated by the conventional tumor debulking followed by chemotherapy [4]. However, this is not the case in patients treated with neoadjuvant therapy.…”

The optimal time for surgery in women with serous ovarian cancer

“…Notably, chemotherapy Time to clinical recurrence, mo can affect the gross morphologic appearance of tumour tissue and surgical planes, which could lead to anatomic variability and render the assessment of residual disease and optimal surgical excision challenging. 40 Finally, when stratifying patients by platinum sensitivity, the negative impact of neoadjuvant chemotherapy on survival is noted. It is well known that patients with platinumresistant disease have significantly worse survival.…”

Phase II/III Study of Intraperitoneal Chemotherapy after Neoadjuvant Chemotherapy for Ovarian Cancer: NCIC CTG OV.21

“…Chemotherapy-induced fibrosis is less extensive • after 3 cycles than after 6 cycles, thus easing surgical resection 19 .…”