Tumor regression grading of gastrointestinal carcinomas after neoadjuvant treatment

Abstract

Multimodal therapy concepts have been successfully implemented in the treatment of locally advanced gastrointestinal malignancies. The effects of neoadjuvant chemo- or radiochemotherapy such as scarry fibrosis or resorptive changes and inflammation can be determined by histopathological investigation of the subsequent resection specimen. Tumor regression grading (TRG) systems which aim to categorize the amount of regressive changes after cytotoxic treatment mostly refer onto the amount of therapy induced fibrosis in relation to residual tumor or the estimated percentage of residual tumor in relation to the previous tumor site. Commonly used TRGs for upper gastrointestinal carcinomas are the Mandard grading and the Becker grading system, e.g., and for rectal cancer the Dworak or the Rödel grading system, or other systems which follow similar definitions. Namely for gastro-esophageal carcinomas these TRGs provide important prognostic information since complete or subtotal tumor regression has shown to be associated with better patient's outcome. The prognostic value of TRG may even exceed those of currently used staging systems (e.g., TNM staging) for tumors treated by neoadjuvant therapy. There have been some limitations described regarding interobserver variability especially in borderline cases, which may be improved by standardization of work up of resection specimen and better training of histopathologic determination of regressive changes. It is highly recommended that TRG should be implemented in every histopathological report of neoadjuvant treated gastrointestinal carcinomas. The aim of this review is to disclose the relevance of histomorphological TRG to accomplish an optimal therapy for patients with gastrointestinal carcinomas.

Keywords: gastrointestinal cancer; histopathology; neoadjuvant therapy; tumor regression grade.

Figures

Figure 1

Gross images of esophageal adenocarcinomas with (A) macroscopic significant regression and (B) no macroscopic significant regression after neoadjuvant chemotherapy.

Figure 2

Histologic findings of tumors treated by neoadjuvant (radio) chemotherapy. (A) Fibrosis replacing previous large parts of the tumor which is evident only by scattered residual tumor glands (Hematoxylin and Eosin (HE) stain, 10×); (B) Acute necrosis (HE stain, 10×); (C) Acellular mucin lakes (HE, 20×); (D) Foamy histiocytes and resorptive changes with cholesterol clefts and chronic inflammation (HE, 20×); (E) Regressive tumor gland adjacent to a better preserved viable gland (HE, 25×); (F) High grade cellular atypia in regressive tumor glands. Note the intratubular histiocytes as sign of resorption (HE, 40×).

Figure 3

Examples of tumor regression grades according to Becker. (A) TRG 1a complete regression. This image would be classified as TRG 1 according to Mandard and TRG 4 according to Dworak. (B) TRG 1b <10% residual tumor. Mandard TRG would be 2, Dworak TRG 3. (C) TRG 2 10–50% residual tumor. Mandard TRG would be 3, but 2 could also be possible since there is no strict definition of “scattered tumor cells” and “preponderance of fibrosis”; Dworak TRG would be 2: the term “scattered tumor cells” is by complemented by “histologically slightly recognizable.” (D) TRG 3 >50% residual tumor. Mandard TRG would be 4 or 5 and Dworak 0 or 1 since one can appreciate fibrotic stands which could be preexisting desmoplasia or regression.