Recurrent atypical antiglomerular basement membrane nephritis in the kidney transplant.

Atypical antiglomerular basement membrane (anti-GBM) nephritis can be defined as linear GBM staining for monotypic or polytypic immunoglobulin (Ig) by immunofluorescence (IF) without a diffuse crescentic pattern. We describe the clinicopathologic features of 6 patients (18 biopsies) in this first series of recurrent atypical anti-GBM nephritis after kidney transplantation. Recurrent glomerulonephritis occurred at a mean of 3.8 months posttransplant (range 1-7 months). Three index biopsies were for clinical indication, and 3 were protocol biopsies. Glomerular histologic changes were mild, with 2 showing segmental endocapillary hypercellularity, 1 focal glomerular microangiopathy, and the others no significant glomerular histologic changes. All 6 allografts showed monotypic linear glomerular Ig staining by IF: IgG kappa (n = 2), IgG lambda, IgA kappa, IgA lambda, and IgM lambda. Follow-up biopsies were available for 5 patients and showed similar histologic and IF findings without evidence of significant progression. No patients had detectable serum anti-GBM antibody or monoclonal proteins. The mean serum creatinine level on follow-up (24-62 months posttransplant) was 1.8 (range 0.93-2.77) mg/dL; no grafts were lost to recurrent disease. This series demonstrates that monotypic atypical anti-GBM recurs in the allograft and supports the idea that this disease is due to a circulating monoclonal protein.

HISTOLOGIC FINDINGS IN VITREORETINAL LYMPHOMA: Learning From Enucleation Specimens.

PURPOSE: We aimed to describe the clinical and histologic findings in a few enucleation cases with intraocular lymphoma. METHODS: Retrospective review of pathology files from a 22-year period identified cases with intraocular lymphoma among all enucleation specimens. Patient demographics, clinical findings, laboratory results, radiographic studies, and indication for enucleation were abstracted from electronic health records; slides were reviewed. RESULTS: Four patients (three women and one man; age range, sixth through eighth decades of life) underwent enucleation with a final diagnosis of intraocular lymphoma. Two patients with primary vitreoretinal large B-cell lymphomas had been treated for refractory uveitis. Specimens showed retinal and subretinal infiltrates by atypical large B-lymphocytes and rare neoplastic cells in the vitreous. The remaining two patients had systemic lymphoproliferative disorders. One patient had chronic lymphocytic leukemia and floaters in his eye; vitreoretinal lymphoma developed, consistent with intraocular Richter transformation. The other had diffuse large B-cell lymphoma in remission; however, blurred vision developed, she was treated for panuveitis without improvement, and was later found to have ocular involvement by diffuse large B-cell lymphoma. CONCLUSION: Our series details the unusual circumstances when an eye is removed for intraocular lymphoma. Different patterns of ocular tissue involvement were observed when we compared primary and secondary lymphomas.

Artificial Intelligence Advances in Transplant Pathology.

Transplant pathology plays a critical role in ensuring that transplanted organs function properly and the immune systems of the recipients do not reject them. To improve outcomes for transplant recipients, accurate diagnosis and timely treatment are essential. Recent advances in artificial intelligence (AI)-empowered digital pathology could help monitor allograft rejection and weaning of immunosuppressive drugs. To explore the role of AI in transplant pathology, we conducted a systematic search of electronic databases from January 2010 to April 2023. The PRISMA checklist was used as a guide for screening article titles, abstracts, and full texts, and we selected articles that met our inclusion criteria. Through this search, we identified 68 articles from multiple databases. After careful screening, only 14 articles were included based on title and abstract. Our review focuses on the AI approaches applied to four transplant organs: heart, lungs, liver, and kidneys. Specifically, we found that several deep learning-based AI models have been developed to analyze digital pathology slides of biopsy specimens from transplant organs. The use of AI models could improve clinicians' decision-making capabilities and reduce diagnostic variability. In conclusion, our review highlights the advancements and limitations of AI in transplant pathology. We believe that these AI technologies have the potential to significantly improve transplant outcomes and pave the way for future advancements in this field.

The Utility of Bronchoscopy in Hydralazine-Induced ANCA-Associated Vasculitis.

Hydralazine is a vasodilator used for the management of hypertension, heart failure, and hypertensive emergencies in pregnancy. It has been implicated in the causation of drug-induced lupus erythematosus (DLE) and rarely with ANCA-associated vasculitis (AAV), which may present as a pulmonary-renal syndrome and be rapidly fatal. Herein, we describe a case of hydralazine-associated AAV presenting as acute kidney injury with the use of early bronchoalveolar lavage (BAL) with serial aliquots to aid with diagnosis. Our case highlights how, in the correct clinical setting, BAL can act as a rapid diagnostic test to help guide quicker treatment to allow for better patient outcomes.

Stevens-Johnson syndrome precipitated by Moderna Inc. COVID-19 vaccine: a case-based review of literature comparing vaccine and drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis.

The Moderna COVID-19 vaccination was approved for use in the United States in December of 20201 and since that time massive public health efforts have been made to vaccinate patients against the COVID-19 infection. Adverse reactions from the vaccination are well-reported and include both local skin reactions, such as pain, swelling, and erythema at the injection site, as well as systemic reactions including fever, malaise, headache, muscle aches, drowsiness, nausea, and vomiting. While severe serious cutaneous adverse reactions, such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), remain rare; two cases of SJS/TEN related to COVID-19 vaccination have been reported. We herein review the two previously reported cases of SJS/TEN and report the first case of SJS precipitated by the Moderna Inc., MRNA 1273 COVID-19 vaccination in the United States. Although we review potential adverse reactions to vaccination, the benefits of COVID-19 vaccination outweigh the risks based on current data. Cases should be reported to the Vaccine Adverse Event Reporting System (https://vaers.hhs.gov/) to help public health officials recognize and track these severe but rare adverse events.

Impact of Pregnancy on GFR Decline and Kidney Histology in Kidney Transplant Recipients.

INTRODUCTION: Women with advanced kidney disease are advised to wait until after transplant to pursue pregnancy, but the impact of pregnancy on estimated glomerular filtration rate (eGFR) decline and kidney histology is unclear. METHODS: We identified a cohort of women aged 18 to 44 years at transplant from 1996 to 2014 at our 3-site program (N = 816) and determined whether they had a pregnancy >20 weeks gestation post-transplant by chart review. Outcomes included rate of change in eGFR after pregnancy, changes in kidney histology before and after pregnancy, graft failure, and 50% reduction in eGFR. RESULTS: There were 37 women with one or more pregnancies lasting longer than 20 weeks gestation post-transplant. Comparing women with and without pregnancy post-transplant, there was a significant increase in the rate of eGFR decline after pregnancy (-2.4 ml/min per 1.73 m2 per year vs. -1.9 ml/min per 1.73 m2 per year in women with no pregnancy, P < 0.001). Pregnancy did not affect the risk of graft failure, death-censored graft failure, or 50% reduction in eGFR. CONCLUSION: Pregnancy affects the rate of eGFR decline in the allograft. Postpregnancy biopsy findings revealed an increase in vascular injury, which could be a potential mechanism. We did not find a significant increase in risk of graft failure or reduction in eGFR by 50% owing to pregnancy.

Metastatic prostate adenocarcinoma to cervical lymph nodes: an unusual diagnosis on fine-needle aspiration biopsy.

INTRODUCTION: Metastatic prostatic adenocarcinoma (PAC) has mostly involved the pelvic lymph nodes; metastases to the cervical lymph nodes are exceedingly rare. MATERIALS AND METHODS: A retrospective review of cytopathology files (January 1990 to March 2019) identified 13 cases of metastatic PAC to cervical lymph nodes diagnosed using fine-needle aspiration biopsy (FNAB). The clinical and demographic information were collected from the electronic medical records, and the slides were reviewed. RESULTS: A total of 13 male patients with a mean age at FNAB 69 years (range, 61-86 years); 12 patients had a known history of PAC. In the patient without a history of PAC, the FNAB finding had been misinterpreted as papillary thyroid carcinoma. The interval between the original diagnosis and cervical lymph node metastasis was 98.5 months (range, 1-288 months). Most involved the left side (85%). Most smears had a clean background with few lymphocytes (46%) and numerous cellular clusters in flat sheets and acini (62%) and were composed of polygonal cells (46%) with round-oval shaped nuclei and indistinct cell borders (92%). The cytoplasm was granular (61%) or scanty (46%). The nuclei were uniform, size ≥2 times that of a neutrophil (69%). Prominent nucleoli and anisonucleosis were seen in 54% of cases; cellular pleomorphism was infrequent (30%). Immunostains confirmed the prostate origin in 7 tissue cores. CONCLUSIONS: Metastatic PAC to the cervical lymph nodes occurs infrequently. If the history is unknown, cases can be misdiagnosed as metastases from cervical neoplasms. The findings indicating metastatic PAC to the cervical lymph nodes on FNAB include involvement of left-sided cervical lymph nodes in elderly male patients and cellular smears composed of uniform polygonal cells, arranged in flat sheets and acini, with granular cytoplasm, indistinct cell borders, and round-oval nuclei with prominent nucleoli.

Genomics Integration Into Nephrology Practice.

RATIONALE & OBJECTIVE: The etiology of kidney disease remains unknown in many individuals with chronic kidney disease (CKD). We created the Mayo Clinic Nephrology Genomics Clinic to improve our ability to integrate genomic and clinical data to identify the etiology of unexplained CKD. STUDY DESIGN: Retrospective study. SETTING & PARTICIPANTS: An essential component of our program is the Nephrology Genomics Board which consists of nephrologists, geneticists, pathologists, translational omics scientists, and trainees who interpret the patient's clinical and genetic data. Since September 2016, the Board has reviewed 163 cases (15 cystic, 100 glomerular, 6 congenital anomalies of kidney and urinary tract (CAKUT), 20 stones, 15 tubulointerstitial, and 13 other). ANALYTICAL APPROACH: Testing was performed with targeted panels, single gene analysis, or analysis of kidney-related genes from exome sequencing. Variant classification was obtained based on the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines. RESULTS: A definitive genetic diagnosis was achieved for 50 families (30.7%). The highest diagnostic yield was obtained in individuals with tubulointerstitial diseases (53.3%), followed by congenital anomalies of the kidney and urological tract (33.3%), glomerular (31%), cysts (26.7%), stones (25%), and others (15.4%). A further 20 (12.3%) patients had variants of interest, and variant segregation, and research activities (exome, genome, or transcriptome sequencing) are ongoing for 44 (40%) unresolved families. LIMITATIONS: Possible overestimation of diagnostic rate due to inclusion of individuals with variants with evidence of pathogenicity but classified as of uncertain significance by the clinical laboratory. CONCLUSIONS: Integration of genomic and research testing and multidisciplinary evaluation in a nephrology cohort with CKD of unknown etiology or suspected monogenic disease provided a diagnosis in a third of families. These diagnoses had prognostic implications, and often changes in management were implemented.

A Rare Case of Prostate-Specific Antigen-Producing Metastatic Parotid Adenocarcinoma Developing Androgen Receptor Resistance.

A 62-year-old man presented with a rising serum concentration of prostate-specific antigen (PSA) to 53.3 ng/mL (to convert to µg/L, multiply by 1) and a PSA doubling time of 2.6 months. Computed tomography, fluorodeoxyglucose-positron emission tomography, and C-11 choline positron emission tomography demonstrated a parotid mass with innumerable lytic bone lesions and diffuse metastatic disease to the neck and mediastinal lymph nodes. Mediastinal lymph node biopsy revealed salivary ductal adenocarcinoma that produced PSA and demonstrated androgen receptor sensitivity. The patient had a prolonged clinical benefit to first- and second-line hormone therapy, and his PSA levels correlated with treatment response, development of hormone resistance, and progression. In summary, urologists, pathologists, and primary care providers should be aware that a rising PSA level in the setting of a head and neck mass in a patient without a history of prostate cancer does not constitute a diagnosis of metastatic prostate adenocarcinoma and that other primary tumors should be considered and a broader imaging and pathologic evaluation is indicated.

Diagnostic value of imprint cytology testing in kidney tumors: review of 200 cases.

INTRODUCTION: Previous investigations have studied the importance of imprint cytology (IC) testing of core needle biopsy (CNB) from various organs. We have presented the largest series, to the best of our knowledge, of IC testing of CNB for patients with kidney tumors. MATERIALS AND METHODS: The present retrospective study (January 1, 2015, through January 30, 2016) identified laboratory information through a computer search of the cytology archived reports for 200 consecutive IC testing with CNB for renal tumors cases. A board-certified cytopathologist and cytology-trained fellow reviewed the IC testing and CNB slides and rendered them as nondiagnostic, positive for malignancy, negative for malignancy, positive for neoplasm, or atypical. The tumors were graded using the International Society of Urological Pathology grading system. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: The IC testing cases classified as atypical (n = 53) or positive for neoplasm (n = 28) were evaluated separately because of the ambiguous morphologic characteristics. Of the other 119 cases, IC testing classified 95 (80%) as positive for malignancy, 5 (4%) as negative for malignancy, and 19 (16%) as nondiagnostic. The corresponding CNB histologic diagnoses showed that 85 of 95 cases (89%) were true positive for malignancy. Of these 85 cases, 45 (53%) were low grade, 21 (25%) were high grade, and 19 (22%) were ungraded. The corresponding sensitivity, specificity, and accuracy were 85%, 11%, and 58%, respectively. The 53 IC-identified atypical cases were more likely to be malignant (n = 40; 75%). Of the remaining IC testing atypical cases, 12 (23%) were negative for malignancy and 1 (2%) was nondiagnostic. Of the 28 cases positive for neoplasm using IC, 13 (46%) were positive and 15 (54%) were negative for malignancy. CONCLUSIONS: The relatively low diagnostic value of IC testing for renal tumors showed it to be less powerful for screening than its use in other organs.