Detection of Intratumor Heterogeneity in Modern Pathology: A Multisite Tumor Sampling Perspective

Abstract

Current sampling protocols of neoplasms along the digestive tract and in the urinary bladder have to be updated, as they do not respond to the necessities of modern personalized medicine. We show here that an adapted version of multisite tumor sampling (MSTS) is a sustainable model to overcome current deficiencies in digestive and bladder tumors when they are large enough so as to make unaffordable a total sampling. The new method is based on the divide-and-conquer algorithm and includes a slight modification of the MSTS, which proved to be useful very recently in clear cell renal cell carcinoma. This in silico analysis confirms the usefulness of MSTS for detecting intratumor heterogeneity (ITH) in tumors arising in hollow viscera. However, MSTS does not seem to improve routine traditional sampling in detecting tumor budding, extramural venous invasion, and perineural invasion. We conclude that (1) MSTS is the best method for tumor sampling to detect ITH balancing high performance and sustainable cost, (2) MSTS must be adapted to tumor shape and tumor location for an optimal performance.

A Molecular Study of Solid Pseudopapillary Neoplasm of the Pancreas in a Pediatric Patient

“…The intra-tumor heterogeneity is recognized as a process with great clinical importance and is related to pathological observation of different tumoral areas [24] associated with cancer progression, resistance to therapy, and recurrences [24,25]. In our study, we observed the heterogeneous morphological aspect of SPNP by gross and histopathological examinations.…”

“…A recent report emphasizes the importance of histopathological and molecular analysis of different fragments of the same tumor to obtain a better detection of intra-tumoral heterogeneity [26]. Some authors have used this system in the evaluation of tumors of the urinary bladder, stomach and large bowel [24]. However, for pancreatic neoplasms and especially…”

The Impact of Tumor Eco-Evolution in Tumor Sampling

“…In this particular setting, the anatomical barrier represented by the muscularis propria forces the tumors to grow with their long axes parallel to the wall of the viscera forming tumors with plate-like shapes and not like spheroids as happens in the kidney, liver or other solid organs. Instead of tissue cubes, the sampling model here gets tissue bars including the whole thickness (from the lumen to the perivisceral adipose tissue) of the viscera [45]. MSTS has obtained here also better performances in detecting ITH compared with routine sampling [45].…”

“…Instead of tissue cubes, the sampling model here gets tissue bars including the whole thickness (from the lumen to the perivisceral adipose tissue) of the viscera [45]. MSTS has obtained here also better performances in detecting ITH compared with routine sampling [45].…”

The Impact of Tumor Eco-Evolution in Renal Cell Carcinoma Sampling

“…In this particular setting, the anatomical barrier represented by the muscularis propria leads the tumors to grow with their long axes parallel to the wall of the viscera forming tumors with plate-like shapes, and not like spheroids as happens in the kidney, liver or other solid organs. Instead of tissue cubes, the sampling model here gets tissue bars including the whole thickness (from the lumen to the perivisceral adipose tissue) of the viscera [53]. MSTS has obtained here also better performances in detecting ITH compared with routine sampling [53].…”