Discovered cancers at postmortem donor examination: A starting point for quality improvement of donor assessment.

BACKGROUND: clinical and imaging investigations allow a detailed assessment of an organ donor, but a quota of cancer still elude detection. Complete autopsy of donors is even less frequently performed, due to economic issues and increasing availability of high-quality imaging. The aim of this study is to gather evidence from the literature on donor malignancy discovered at autopsy following organ donation and to discuss the utility and limitations of autopsy practice in the field of transplantation. METHODS: A systematic search according to PRISMA guidelines was carried out in Pubmed and Embase databases until September 2020 to select articles with reporting of cancer discovered in a donor at postmortem examination. Cancer discover in not-transplant setting were excluded. A descriptive synthesis was provided. RESULTS: Of 7388 articles after duplicates removal, 56 were included. Fifty-one studies reported on complete autopsy, while 5 dealt only with limited autopsy (prostate and central nervous system). The number of autopsies ranged between 1 and 246 with a total of 823 autopsies performed. The most frequent cancer discovered at autopsy was lymphoma (n = 13, 15%), followed by renal cell carcinoma (RCC) (n = 11, 13%), non-small cell lung cancer (NSCLC) (n = 10, 11%), melanoma (n = 10, 11%), choriocarcinoma (n = 6, 7%) and glioblastoma (GBM) (n = 6, 7%). CONCLUSIONS: Lymphoma and melanoma are still difficult-to-detect cancers both during donor investigation and at procurement, whilst prostate cancer and choriocarcinoma are almost always easily detected nowadays thank to blood markers and clinical examination. There have been improvements with time in pre-donation detection procedures which are now working well, particularly when complete imaging investigations are performed, given that detection rate of CT/MRI is high and accurate. Autopsy can play a role to help to establish the correct donor management pathways in case of cancer discover. Furthermore, it helps to better understand which cancers are still eluding detection and consequently to refine guidelines' assessment procedures.

Rapid screening for malignancy in organ donors: 15-year experience with the Verona "Alert" protocol and review of the literature.

BACKGROUND: Prevention of transmission of malignancy from donors to recipients is an aim of donor assessment. We report the most stringent interpretation of the Italian National Guidelines. METHODS: A two-step ALERT process was used: ALERT1 consisting of clinical, radiological, and laboratory tests; ALERT2, consisting of intraoperative assessment in suspicious lesions. RESULTS: Four hundred of 506 potential deceased donors entered the ALERT system. Forty-one of 400 (10%) donors were excluded due to unacceptable risk of transmission. Of the remaining 359 193 required histopathology, which excluded malignancy or determined acceptable risk in 161/193 (83%). Thirty-five malignancies were identified: 19 (54%) at ALERT1, four (11%) at ALERT2, nine (26%) picked up at ALERT1 and confirmed by ALERT2. Three (9%) were missed by ALERT and diagnosed at postmortem examination. Prostate (n=12%, 34%) and renal cell (n=7%, 20%) were the most frequent carcinomas. The majority (92%) of prostate adenocarcinomas were of low risk and donation proceeded compared to 43% of renal carcinomas. Four renal carcinomas, two breast carcinomas, and a single case of nine different malignancies excluded donation. Positive ALERT donors had statistically more malignant reports than negative ALERT donors (P=<.05). CONCLUSION: Histopathology is an essential component of the multidisciplinary assessment of donors.

De Novo Renal Neoplasia After Kidney Transplantation According to New 2016 WHO Classification of Renal Tumors.

BACKGROUND De novo renal neoplasia developing after kidney transplantation at Verona Kidney Transplant Center were reviewed according to new 2016 WHO Renal Tumor Classification. MATERIAL AND METHODS Primary renal tumors developed in native or transplanted kidneys de novo following renal transplantation were retrieved and histologically reviewed by three expert uropathologists. Immunoexpression of the diagnostic antigens CD13, CD10, CK7, CK34bE12, AMACR, CAIX, AE1/AE3, CK14, GATA-3, HMB-45, cathepsin-k, S100A1, and parvalbumin was assessed. Predictive antigens ph-mTOR and ph-p70S6k were also tested. RESULTS Two thousands and sixteen kidney transplantations have been carried out from 1968-2015. Follow-up was available per 1,646 patients (mean 8.4 years). We observed 16 cases of de novo renal neoplasia arising in patients 16 to 286 months post-transplantation. Nine clear cell, two papillary RCCs and a single case of the new WHO entity denominated "acquired cystic disease-associated RCC" were identified in native kidneys. Another new WHO tumor entity called "clear cell papillary RCC" was diagnosed and a new variant of papillary RCC with diffuse clear cytoplasm was also identified. The majority of tumors were low stage and low grade according to the new ISUP grading system. Seven patients were additionally treated with mTOR inhibitors. Post-cancer follow-up ranged from 62 to 281 months. One patient showed a recurrence (a lung metastases) and died. Of the remaining patients, three died of non-cancer-related causes. CONCLUSIONS The application of the new WHO 2016 classification has importance as it identifies new (18% of tumors) morphotypes that are likely to behave in a less aggressive fashion.

Digital reporting of whole-slide images is safe and suitable for assessing organ quality in preimplantation renal biopsies.

Digital pathology allows networks of "remote" specialist pathologists to report the findings of preimplantation kidney biopsies. We sought to validate the assessment of preimplantation kidney transplant biopsies for diagnostic purposes using whole-slide images according to the recommendations of the College of American Pathologists. Sixty-two consecutive, previously reported, preimplantation kidney biopsies were scanned using the ScanScope Digital Slide Scanner at 0.5 µm/pixel (20× objective). The slides were assessed for percent glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing using the Remuzzi criteria by two pathologists, one using glass slides and the other using the whole-slide images viewed on a widescreen computer monitor. After a 2-week washout period, all of the slides were re-assessed by the same pathologists using the opposite mode of reporting to that used in the first evaluation. Very high glass-digital intraobserver concordance was achieved for the overall score and for individual grades by both pathologists (κ range, 0.841-0.973). The overall scores obtained by both pathologists and using both methods were identical. The times needed to assess the biopsies were 14 minutes when using a light microscope and 18 minutes, including scanning time, which averaged 2 minutes 20 seconds per slide, when using digital microscopy. Digital microscopy is a reliable, fast, and safe method for the assessment of preimplantation kidney biopsies.