Shining a Light on Small Biopsy Handling

By: Siobhan Fairgreaves​, CellPath

Biopsies of all shapes and sizes come with their own special set of problems, with small tissues particularly prone to manual handling issues. The difficulties associated with the manipulation of tiny delicate samples and the fear of tissue escaping from cassettes are well known for many in the field.

When focusing on small biopsies specifically, there are many opportunities for tissues to be damaged or affected throughout the histology process. Sources of damage can come from initial fixation which can often mean over fixation for tiny biopsies. Handling with tweezers can also be difficult for staff, as well as potentially impacting the tissue. This damage can come from over exertion of pressure through the tweezers or from difficulty orientating such tiny samples meaning they may be overhandled.

Opportunities for problems to develop can then continue depending on the type of processing which is used. The size of these biopsies creates potential for samples to escape if specialist cassettes are not used. Those that do survive may suffer damage from impression on the tissue by a cassette or biopsy pad which results in artefact that may not be seen until presented to the Pathologist.

Manufacturers are keen to develop solutions which will help reduce the risk of damage to or loss of these delicate specimens. The industry has now reached a stage where solutions abound but each is accompanied by their own limitations.

Dr Max Maza (MSc, BSc, MRSC) and Mr Colin John Brewer (F.I.M.L.S.) will be discussing the common problems encountered when handling small biopsies and the opportunities and limitations of current solutions at their workshop “How to Improve Handling of Small Biopsies” at the National Society of Histotechnology Symposium/Convention in New Orleans in September 2019. They will then introduce some more recent innovations which are being brought to market.

Current solutions include lens paper, biopsy bags, foam pads, cell blocks and specialist cassettes or capsules. Through their use, excellent results can be achieved and important clinical benefits have been seen for many years. Their use allows for the integration of small biopsy handling into standard tissue processing whilst protecting the biopsies.

The workshop presented by Max and Colin will discuss the differences between the current options and explore their benefits and limitations, covered briefly below.

Lens paper can be a cost effective option as several samples can be contained together in one piece of paper. This makes it a popular choice for prostate biopsy cases when several tissue samples will be taken before inserting into formalin. Unfortunately, in this time tissue can dry out. Some laboratories report that it can be difficult to retrieve the sample from the lens paper.

Biopsy bags are best suited for liquid samples as the whole sample can be poured through the fine mesh and the cells will be retained whilst excess fluid is drained. This technique requires some practice and can be tricky to master at first. As with lens paper, it can sometimes be difficult to remove cells from the bag when required.

Foam pads offer excellent sample security and allow for good reagent flow. Variance in pore size between pads from different sources can impact reagent flow and the presence of artefact. There is potential for artefact to be caused by impression of the sponge- particularly if the cassette is overfilled.

Cell blocks are a labor intensive method with several stages. Their use is only suitable for liquid cytology. The process requires sample extraction and then an additional step of spinning the sample in a centrifuge to form a pellet of cells. Whilst time intensive to produce, this method is useful for studying scant samples.

Specialist cassettes come in a range of styles and offer different functions. Some cassettes protect biopsies by having small holes to prevent the biopsies escaping and other use a fine mesh which ensures good reagent flow as well as security. More specialist cassettes may even contain a sectionable matrix to help minimize the amount of manual handling required. These options can be expensive and some may require a closed system to operate but can provide excellent results.

In this post I have described some of the more common methods used to protect small biopsies, however laboratories may find they need to adapt the standard techniques available to best suit their available equipment. Budgetary concerns will also apply as laboratories must balance the impact of introducing potentially labor intensive technologies against the obvious benefit of protecting biopsies.

As well as discussing the current solutions and their key features, Max and Colin will introduce an innovative solution, the Lumea Inc. Bx Chip, which seeks to eliminate a large proportion of the risk associated with manual handling of small biopsies.

BxChip will allow clinicians to insert prostate biopsies into a sectionable matrix direct from the biopsy gun in the procedure room itself. The chip can then be placed into a cassette and dropped into a pot of formalin without any manual handling of the biopsy. Each chip can contain at least 6 cores.

Research shows great promise for this device, particularly in minimizing non-linear fragmentation and specimen loss of these friable specimens. Intact core length is found to be greatly increased and the diagnostic benefit of being able to observe much more of the tissue intact is that the features of the tumor can be better understood. Finally, the vast reduction in laboratory time and resource required results in cost savings when the BxChip is implemented.

To learn more about new and existing solutions to the problems created by small biopsy handling please visit the “How to Improve Handling of Small Biopsies” workshop led by Max and Colin at this year’s NSH Symposium/Convention.

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