VDx now offers PARR testing in-house on formalin-fixed tissue.
Is this cat’s chronic lymphocytic enteritis really chronic IBD or is this early small cell lymphoma? Is this dog’s splenic nodule or enlarged lymph node benign or really indolent lymphoma? VDx is here to help! VDx is currently the only private, non-academic laboratory in the U.S. to offer PARR testing on formalin-fixed tissue in addition to cytology samples.
PCR for Antigen Receptor Rearrangement (aka PARR or Clonality PCR) is a tool which has greatly increased the sensitivity of diagnosing lymphoma in difficult cases, helping diagnose lymphoma earlier and with less invasive sampling.
This technique is based on the fact that during maturation, lymphocytes undergo a series of genetic alterations (VDJ rearrangements) which are unique from cell to cell, and ultimately culminate in almost unlimited variety among the antigen receptors on B and T lymphocytes. By using PCR primers to amplify the area encoding diversity of the immunoglobulin heavy chain (IgH) of B cells and the gamma subunit of the T cell receptor of T cells (TCRγ), DNA from clinical specimens can be analyzed to determine whether the lymphocytes in a specimen share identical antigen receptors (ie are “clonal”), or whether they are genetically different (i.e. “polyclonal”). As suggested by the clonal theory of cancer, a clonal expansion is very highly suggestive of neoplasia.
PARR testing is especially useful when the results of biopsy or cytology evaluation are inconclusive or are suggestive, but insufficient for a definitive diagnosis, of lymphoma.
PARR should be conducted as part of a stepwise process, which begins with clinical assessment (presentation, history and other lab work) along with microscopic evaluation of tissue (cytology or biopsy) and in some cases immunohisto/cytochemistry.
It can be tempting to view PARR as a shortcut to diagnosis of lymphoma. However, when steps are omitted (e.g. biopsy or cytology, immunohistochemistry), misdiagnosis or errors in interpretation may sometimes occur. To prevent this, PARR evaluation at VDx always includes morphologic review by a pathologist.
Immunohistochemistry (aka IHC, for biopsies) and immunocytochemistry (aka ICC, for cytologies) are techniques utilizing antibodies to specific cellular components (such as parts of the B and T cell antigen receptors) to determine the phenotype or lineage of cells in a specimen. IHC/ICC allows determination of the types of cells that are present but cannot directly differentiate neoplasia vs. reactive change (i.e. it cannot determine whether a population of T or B cells is genetically identical). However, IHC/ICC is used as an adjunct to evaluation of cellular morphology and assessment of tissue architecture (ie cytology and biopsy evaluation) and to assist in the interpretation of PARR results. In some difficult lymphoma diagnoses, IHC/ICC must also be performed and interpreted in conjunction with PARR to arrive at an accurate diagnosis. The pathologist will advise if this is the case. Omitting IHC/ICC can lead to increased risk of misinterpretation of PARR results.
Flow cytometry (or “flow”), is similar to IHC, but performed on fluid samples or cell suspensions. Like IHC/ICC, flow also uses antibodies to detect various cell surface markers, but because flow is performed on unfixed cells, a greater array of cell markers can be evaluated, allowing more fine differentiation among various classes of lymphocytes. Certain patterns are very strongly associated with various lymphoid malignancies. However, unlike IHC, which allows evaluation of phenotype in conjunction with tissue architecture, flow does not allow assessment of tissue architecture or cell morphology, unless biopsy or cytology are also performed, thus flow results should not be interpreted in a vacuum. For proper interpretation, flow results must be evaluated in conjunction with other clinical variables, including presentation, history and morphologic assessment.
VDx also offers 2nd opinions, including PARR testing, on biopsy or cytology samples previously evaluated at other laboratories.
Materials sent from other laboratories will be consumed during testing, in whole or in part, and cannot be returned to the originating laboratory. To submit samples previously evaluated elsewhere please request the following from the originating laboratory:
Cytology: All stained and unstained cytology slides. VDx will review and chose the best.
Biopsy: Paraffin block(s) (preferred), or at least 10 unstained recuts on positively charged slide from each block.
In addition to a turnaround time of 7-9 working days from sample receipt at the laboratory, the pathologists at VDx will be happy to consult with you prior to sample submission – Our goal is to provide you with a personalized service not available at any other laboratory.
PARR testing at VDx is rendered with a full evaluation by a board-certified pathologist which includes review of biopsy/cytology results and any IHC/ICC of flow cytometry data.
Whether you wish to send a sample directly to us or would like another laboratory to forward case materials to VDx for a second opinion, we’re here to help. We now offer a combination biopsy/cytology and PARR profile for lymphoma cases.
New Client information Form (PDF) (Please complete and submit with sample if new VDx client or fax to 530-753-4055)
VDx PARR information and FAQs (PDF)
Since 2001, the pathologists and staff of VDx Veterinary Diagnostics have focused upon what veterinarians have told us they want out of a laboratory – Accurate results delivered on time, pathologists who don’t “fence sit” and are readily available for consultations, plus a laboratory/customer service staff which actually does what it is going to do. VDx allows you and your staff to focus on what matters most – caring for your patients.
For any inquiries regarding PARR/PCR, please contact us via e-mail at firstname.lastname@example.org or call us at 530-753-4285.