Guess what we do on Friday afternoons…
By: Dr. C . Avila-Casado
The following is just a fictional example, but we spend our Fridays (and everyday) making sure our patients get the best care possible. Read on to see what we do and how we help . . .
(editor’s note – some of the language and terms are a bit difficult for the lay person, so we’ve put easy to understand definitions within brackets. Hope it helps! – JB)
It’s Friday afternoon and when you open the work list you realize that a renal transplant biopsy (a kidney transplant examination) has been collected. You start to worry about the clinical history, the attendant pager (the emergency contact number for the doctor in charge of looking after the patient) and the possibility of rejection.
Is it an ultrarush? (an urgent situation) How come nobody has contacted us before about this case?
You immediately call the Histology Lab and a very kind technologist lets you know that the slides could be ready and IF against C4d is being performed. (A special technique for identifying markers of the immune system by causing them to “light up” / fluoresce against a specific marker for rejection.)
The admission form says “recent elevation in creatinine — biopsy of the kidney allograft – two years after transplant.” (an elevated chemical marker within the blood indicating deteriorating kidney function)
You start looking for the patient clinical history – elevation of creatinine two years after transplant, did the patient stop taking their medication? What was the reason of the previous renal failure: was a native kidney biopsy performed? (Was tissue taken of the patient’s own / original kidney to determine the cause of their kidney failure?)
Who was the donor? What is the immunosuppression regimen? (drugs scheduled to reduce the immune system’s response to a “foreign” kidney.) What are the basal serum creatinine and the trends? (Test results to show how the donated kidney has been functioning since it was transplanted).
By all means, two years after transplant is the time when everything and anything can cause creatinine to rise, including recurrence of the original disease. You look for all this valuable data in the chart until you get the full picture with the slides.
Once the slides arrive, you review the biopsy, just the H&E stain (a popular stain we use in pathology to help emphasize areas within a sample). H&E could be perfect for the assessment of inflammation or any clue of immunological rejection to let the clinician know if some treatment should be prompted installed.
No inflammatory cells are seen in two nice cores of cortex but the glomeruli look hypercellular. (a structure formed by loops of blood vessels for filtering blood within the kidney look like they have more cells than normal).
Hmm, glomeruli can always look hypercellular in an H&E, is it only artifactual? (not real) If at least you could have the PAS or the Silver stains to make your life easy! (Special stains used to identify unique components of the tissue using acids and silver, which are technically difficult and cannot be prepared quickly.)
You go back to your slide and select a higher magnification. Glomeruli must be reviewed one by one, looking at every section, again and again. Yes, there is diffuse subtle mononuclear glomerulitis (a widespread increased white blood cells within the blood vessel loops) and swelling of the endothelial cells (swelling of the lining of the blood vessels).
You discard the diagnoses of anticalcineurin-inhibitor toxicity (toxic effects of immunosuppressive drugs) as there are too much glomerular cells to qualify as just endothelial swelling.
Could be this part of an antibody mediated rejection? (the chemical components of the immune system attacking the “foreign” kidney.)
You review all the vessels again: no endotheliitis; no endarteritis; small vessels show thickening of the vessel wall; arteries show concentric arteriosclerosis; and no inflammatory cells are seen within the walls. You start wondering if these are only chronic changes, but after all, are these chronic changes the result of chronic cellular or antibody mediated rejection?
You consult your watch, 5 o’clock already.
It would be good to review the C4d staining (the specific marker for antibody –mediated rejection) in order to have a better idea of the immunological background (the circulating chemicals made by the immune system) in this biopsy. You go to your slide box and yes, a beautiful yellow page in a slide folder let you know that the C4d with its positive control (the quality control slide) is right there. You turn on the immunofluorescence lamp; let it warm a little and you can’t wait to review the case.
Of course, as specified in your manual, you start reviewing the positive control to assess the quality and sensitivity and as you expected, C4d in the positive control looks spectacular. The case is next and as you suspected a beautiful multi focal staining (diffuse positivity) for C4d is seen along the peripheral of the peritubular capillaries. Pictures are taken before it fades. (As staining is transient)
You can now put everything together as you have no doubt – this could be an early phase of antibody mediated rejection due to the presence of small amounts of chemical components of the immune system attacking the foreign kidney.
You call the clinician immediately to let him know what your thoughts are: the presence of occult donor specific antibodies needs be checked. (The presence of small amounts of chemical components of the immune system attacking the foreign kidney needs to be elucidated.)
You describe what you have found in the report and finally you take the light microscopy pictures. It’s now seven o’clock and you’re ready to go home and enjoy a peaceful weekend, knowing that the effort you have invest will result in a patient that is about to receive the care he or she requires.
Trust us, pathologists are doctors!