Three-dimensional reconstruction of sentinel lymph nodes with metastatic breast cancer indicates three distinct patterns of tumour growth

Emma C Paish ^1*, Andrew Green ², Emad A Rakha ¹, Douglas Macmillan ¹, John Maddison ³ and Ian O Ellis ¹

¹ Nottingham University Hospitals, United Kingdom
² University of Nottingham, United Kingdom
³ Medical Solutions Plc, United Kingdom

^* To whom correspondence should be addressed. E-mail: mrxecp{at}nottingham.ac.uk.

Accepted 27 February 2009

Abstract

Purpose: A better understanding of the biology of nodal metastatic disease is of indisputable value. Three-dimensional (3D) serial section alignment and reconstruction techniques can be used for visualisation of nodal metastasis and could provide better understanding of disease growth patterns.

Methods: Nineteen tumour-involved sentinel nodes (SLNs) from breast cancer patients were serially-sectioned, immunohistochemically stained, and digitally scanned. Digital image alignment and Voxel-based rendering was used to construct informative 3D visual representations of metastatic tumour distribution within involved nodes.

Results: The 3D reconstruction technique was successful and informative. The reconstructions of all nineteen SLNs enabled the metastatic tumour cells to be viewed infiltrating normal SLN tissue from all angles. Metastases were present at the afferent lymphatic pole in 17/19 cases, confined to the afferent pole only in 7 cases, located at the efferent pole in 12/19 cases, and efferent pole only in just 2 cases. Finally, this study made the novel observation that metastatic growth occurs in three distinct patterns; sinusoidal, nodular and diffuse.

Conclusions: This methodology provides improved understanding of metastatic disease development and potentially could be used to develop strategies to improve techniques for its routine detection. Further studies are required in order to evaluate the prognostic and biological significance of the growth patterns identified.