New Avenues in prostate needle biopsy processing

No other biopsy processing procedure has generated so many proposals for development as prostate needle biopsy. Different kinds of automation are the main trend. All suggestions are targeting the grossing/embedding areas to eliminate the middleman. Unfortunately, all presented below materials lack reliable methodology description in peer reviewed publications.

The notion of embedding automation has some history starting with Williamson patent.  In the patent application filed in 1996 and issued in 2007, Warren Williamson IV et al. proposed a fluoropolymer sectionable cassette, or in original description “tissue trapping platform” where “a tissue biopsy sample is placed on a tissue trapping supporting material that can withstand tissue preparation procedures, and which can be cut with microtome”. (1)

Sakura Finetek U.S.A., Inc. implemented Williamson’s patent idea in Tissue-Tek® AutoTEC® Automated Embedding System with Tissue-Tek® Paraform® Sectionable Cassette System. (2) However, still today it is far away from the established practice. The main technological problem is, as was already noticed by Williamson’s patent, “…to keep the tissue samples in place while in fluid medium of the tissue processor.” All variants of sectionable cassettes offered by Sakura Finetek have this main problem. (3)

Two different approaches to the core immobilization have been suggested. They have in common the sectionability of the cassette’s inserted platform.

QuickMBed TM first suggested a silicone pad, and later a hydrogel pad, that has a flexible base and rows of stems with flared ends on the top of the stems. This sectionable pad had been intended for core biopsies. The grasp of the stems is completely secure. Even if the pad falls on the floor, the specimen remains at the same place. The pad can be placed in a standard cassette. (4) This proposal was abandoned due to a threat of patent infringement litigation from a large automated instrument manufacturer.

The Biopsy ChipTM is an insert in the processing cassette. The chip is a grooved, sectionable 2mm matrix made from a proprietary biomimetic protein polymer. It can be used for aligning the specimens during the biopsy procedure, as well as during grossing. Up to 12 core biopsies can be placed in one individual sectionable matrix for simultaneous processing and sectioning. The chip, loaded with cores, is sandwiched between two foam pads in a tissue cassette to prevent any movement during processing. The biomimetic polymer shrinks during processing to the same extent as the cores themselves that provides immobilization. Upon tissue processing, the chip is embedded and the paraffin block is sectioned. The Biopsy ChipTM was used for the collection and analysis in a number of Romanian hospitals where the multiplex method of prostate biopsy harvesting and processing appeared as an easily applicable and cost-effective method. (5) The insert in the cassette below.






A different approach is used by the semi-automatic prostate specimens downloading system SmartBx technology (6,7) The harvested biopsy is placed onto the specially engineered disposable cassette that is built out of plastic, polyester, and the paper membrane during the manufacturing stage of the cassette.The polyester is part of the technology of downloading the specimen from the biopsy gun’s needle onto the paper membrane. The cassette with adhered (“stick”) to the paper membrane biopsy material is transported in fixative to pathology. In the gross room, the cassette is opened by the grossing person. The necessary measurements and descriptions are made. The proprietary cassette is disposed. The paper with adhered biopsy material is placed into regular tissue processing cassette onto regular polyester pad. It goes through tissue processing. After the tissue processor, the paper with the biopsy material is removed from the cassette and placed biopsy-down into a special SmartBx embedding mold that is paired with a special tamper. In the mold, the cassette is placed on top and cooled as usual.

The SmartBx method abandoned the idea of a sectionable cassette, but solved the main problem of core immobilization during processing through adhesiveness to the matrix (proprietary paper membrane), which is embedded in the paraffin block. This method is at the stage of testing in the USA. Unfortunately, there is no published material on the results of clinical tests using the SmartBx method, including how the block “behaves” during microtomy, as well as how the material is presented on the slide for the pathologist’s review. And the cost of the procedure is much higher than the usual method.

The SmartBx method has a predecessor in the James B. McCormick’s 2006 patent, which suggested a perforated card for receiving a tissue specimen to be processed for histological examination.(8) The card has predetermined porosity for providing passage fluids. The non-adhesive portion of the card includes a thin film material selected from the group consisting of polypropylene, polytetrafluoroethylene, polyethylene, polyester and nylon.  The film “is perforated to have a there through to the absorbent portion of an amount of denatured tissue juice effective for forming a protein bridge between the juice and the absorbent portion for removably fixing the tissue specimen” “Or, in the instance of previously fixed tissue, the penetration and encapsulation by a molten agar or gel that when cool will process and embed for microtome sectioning” (direct quotes from the patent.) Immobilization of the specimen (e.g. prostate core biopsy), which ensures orientation, is the invention’s main point that determines further development of prostate biopsy processing methodology.

Milestone/Klinipath V.P. SYNERGY presented all- in- one system of automatic embedding. According to the website, specimen (prostate biopsy core) is placed at the base of the polyoxymethylene mold; a polyester sponge pad goes on top to maintain the position; the cassette is clipped as a cover of the mold. The mold+cassette assembly is inserted in the Milestone’s DELTA or LOGOS rack for tissue processing. The method is based on Klinipath’s patent. (9)

The New Avenues  presented unfinished for wide implementation products, but it shows the tendency for development. All methods try to provide maximal immobilization of the biopsy material during tissue processing and minimal involvement of the grossing person in sampling or the histotechnologist in embedding. In the case of prostate needle biopsy, the grossing person’s involvement can be as little as possible. However, if the material from the clinic is brought just to the microtome, an important part of specimen navigation is excluded. Sampling situations do occur, which require corrections.


1.Williamson, IV, Warren P. et al.: Apparatus and method for harvesting and handling tissue samples for biopsy analysis. United States Patent Full-Text Image database: 7156814. Accessed February 26,2015

2.Diederichsen Chris, Whitlatch Stephen. Description and Preliminary Results of a Novel Cassette system (Tissue-Tek Paraform Cassette System). HistoLogic 1999 31(2), pp. 28-30

3.Dimenstein IB: Sectionable cassette for embedding automation in surgical pathology. Annals of Diagnostic Pathology 2010; 14:100-106.

4.Dimenstein IB: New Devices for Manual Embedding Orientation. The Journal of Histotechnology 2009; Vol. 32 (3): 123-125.

5. Farcas C.P, Spinu A.D. Petrescu A., Mucat S, at all. High throughput processing and analysis of prostate biopsies for research applications. Revista Romana de Urologie, nr.3/ 2014, vol 13, pp:9-16.


8.Apparatus and method for histological processing of a tissue specimen with means for maintaining the orientation of the specimen throughout the processing tissue. Nov 29, 2005 Jun 8, 2006 Mccormick Scient L L C

9. Method and device for preparing tissue and mould for pretreating tissue material









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