Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases

Abstract

Background: Knowledge that liver tumours preferentially take their blood supply from the arterial blood supply rather than the portal venous system can be used for local delivery of treatment or for embolisation to cut off the blood supply to tumours.

Aims: To present histological evaluation of malignant and non-malignant hepatic tissue of one such therapy, selective internal radiation therapy (SIRT) with yttrium-90 microspheres, to decipher its principal mechanism of action.

Methods: The H&E stained sections of hepatic resection specimens from three patients with liver metastases from colorectal (CRC) cancer, who underwent hepatic surgery 4-9 months following SIRT, were examined and the pathological changes documented.

Results: Resin microspheres were identified in the vascular tumour bed and vessels within the portal tracts of the background liver parenchyma. Microspheres were usually associated with giant cell reaction or histiocytes. In the tumour bed, tumour necrosis, mucinous alteration, collections of foamy histiocytes, ectatic vessels, calcification and fibrosis were observed. There was minimal cellular inflammatory response observed, suggestive of direct radiation injury as a non-immune mediated process.

Conclusions: We describe in detail the spectrum of histopathological changes in malignant tissue and liver parenchyma in patients with metastatic CRC treated with SIRT. Our findings are consistent with the hypothesis that the principal mechanism of action of SIRT appears to be via arterially directed delivery of highly radioactive microspheres in and around the vascular tumour bed rather than by micro-arterial embolisation.

Figure 1

Colour photomicrograph of a liver metastasis. R Douglas Wright developed a way of injecting blue gelatine via the hepatic artery and red gelatine via the portal vein to demonstrate the junction of hepatic artery capillaries and portal venules. Reproduced with permission from the Journal of Pathology and Bacteriology.

Figure 2

H&E section of liver tissue in patient with metastatic colorectal cancer 4 months after selective internal radiation therapy (200×). Shows characteristic microspheres in association with giant cell reaction (block arrow). Surrounding ‘sea’ of foamy histiocytes (fine arrows) is also seen.

Figure 3

Case 1. (A) Representative section of lesion 1 (20×) in segment IV, 40 mm in size, showing minimal tumour response (70% viable tumour cells) and few scattered foci of calcification. (B) Representative section of lesion 2 in left hepatectomy, 12 mm, with partial tumour response (30% viable tumour cells seen in entire lesion sampled). (C) Residual well demarcated metastatic colorectal adenocarcinoma next to responsive area showing fibrosis (20×), calcification and paucicellular fibrinous exudate adjacent to microspheres (D, 100×).

Figure 4

Case 2. Right hepatectomy with two synchronous tumours. (A) Representative section of lesion 1, 15 mm, showing complete pathological response. (B) No viable tumour cells were seen and the ‘intratumoural’ zone contains marked fibrosis, calcification and paucicellular fibrinous exudate. (C) Ectatic vessels with the larger calibre vessels showing hyalinisation and intimal thickening. (D) Gapping ectatic vessels in association with loose fibrinous exudate and foamy histiocytes.

Figure 5

Case 2. Right hepatectomy with two synchronous tumours. (A) Representative section of lesion 2, 10 mm, showing good partial pathological response. (B) (10×) and (C) (100×). Residual tumour (20% viable tumour cells), fibrosis and calcification are seen. (D) Mucinous change and foamy histiocytes (100×) are identified.

Figure 6

Case 3. Right hepatectomy with tumour nodule 40 mm showing good partial pathological response (30% viable tumour cells). (A) Tumour necrosis (10×) with inset (200×), to demonstrate the lack of inflammatory cells such as polymorphs within necrotic debris. (B) Fibrosis and ectatic vessels. (C) Foamy histiocytes in association with haemosiderin pigment. (D) Larger calibre vessels showing tortuosity and intimal alteration.