Biopsy-Based Transcriptomics Support Rejection Monitoring Through Repeated Kidney Allograft Biopsies.

Introduction: Biopsy-based transcriptomics may detect subthreshold signals suspicious for rejection in histologically "rejection-free" biopsies, reflect antirejection treatment responses, and indicate gradual phenotyping of rejection in kidney allograft biopsies.

Methods: We investigated 80 "biopsy series" (baseline and corresponding follow-up biopsies) from 2018 to 2025, assessed by histopathology (Banff classification) and the Molecular Microscope Diagnostic System (MMDx).

Results: Baseline biopsies showed histological rejection, including partial antibody-mediated rejection (AMR) and borderline T-cell-mediated rejection (TCMR) in 55 of 80 cases (69%), with 55% molecular rejection confirmation.

Perinephric myxoid pseudotumor of fat - histopathological and molecular characterization of 3 cases after renal transplantation.

Background: Perinephric myxoid pseudotumor of fat (PMPF) is a rare benign pseudo-neoplastic proliferation of the perinephric and renal sinus adipose tissue. Its pathogenesis is thought to be a reactive process typically associated with neoplastic and non-neoplastic end-stage kidney disease. The distinctive histopathological feature of PMPF is a myxoid process comprising bland, spindled stromal cells interspersed with mature adipose tissue.

Additional Diagnoses Other Than Rejection in the Kidney Allograft Biopsy: Pitfalls for Biopsy-based Transcript Diagnostics.

Background: Biopsy-based transcripts associated with antibody-mediated rejection (AMR) hold promise as substitutes for C4d positivity. However, their utility in cases with additional diagnoses other than rejection remains inadequately studied.

Methods: In our comprehensive analysis of 326 kidney allograft biopsies, assessed by histology and the Molecular Microscope Diagnostic System, we identified 68 cases characterized by additional pathologies, including pyelonephritis (n = 15), BK nephropathy (n = 20), acute interstitial nephritis (n = 5), and glomerular diseases (n = 28).

A Case of Hypocomplementemic Urticarial Vasculitis Syndrome With Severe Renal and Gastrointestinal Involvement.

We present a severe case of hypocomplementemic urticarial vasculitis syndrome (HUVS) and its diagnostic and therapeutic challenges. A 56-year-old male presenting with fever and impaired kidney function was diagnosed with HUVS. Before the initiated treatment was effective, he developed severe colon ischemia, and a subtotal colectomy was required.

HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status.

Hepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E.

Limitations of biopsy-based transcript diagnostics to detect T-cell-mediated allograft rejection.

Background: Isolated tubulitis, borderline changes and isolated arteritis suspicious for histologic T-cell-mediated rejection (hTCMR) remain findings of uncertain significance. Although the Molecular Microscope Diagnostics System (MMDx) has not been trained on those lesions, it was suggested that MMDx might reclassify a subgroup to molecular TCMR (mTCMR).

Methods: In this single-center cohort of 326 consecutive, unselected kidney allograft biopsies assessed by histology and MMDx, we analyzed 249 cases with isolated tubulitis (i0, t1-3, v0; n = 101), borderline changes (according to Banff 2022, v0; n = 9), isolated arteritis (no borderline, v1; n = 37), no inflammation (i0, t0, v0; n = 67) and a positive control cohort (hTCMR, n = 27; mixed histologic rejection, n = 8; both according to Banff 2022; total n = 35).

Too Much of a Good Thing: Severe Hypercalcemia Presenting with Lethargy and Kidney Failure.

We present a case of a 58-year-old man with a history of laryngo-pharyngectomy including bilateral thyroidectomy due to hypopharyngeal cancer presenting with lethargy, acute kidney failure, and hypercalcemia. Milk alkali syndrome was diagnosed given the history of high-dose calcium / vitamin D supplementation after ruling out other causes of hypercalcemia. After initial treatment with normal saline, furosemide and denosumab, the patient developed severe symptomatic hypocalcemia as a rare adverse effect of denosumab.

Molecular diagnosis of antibody-mediated rejection: Evaluating biopsy-based transcript diagnostics in the presence of donor-specific antibodies but without microvascular inflammation, a single-center descriptive analysis.

Biopsy-based transcript diagnostics may identify molecular antibody-mediated rejection (AMR) when microvascular inflammation (MVI) is absent. In this single-center cohort, biopsy-based transcript diagnostics were validated in 326 kidney allograft biopsies. A total of 71 histological AMR and 35 T cell-mediated rejection (TCMR) cases were identified as molecular AMR and TCMR in 55% and 63%, respectively.

Neurologic involvement in cystinosis: Focus on brain lesions and new evidence of four-repeat (4R-) Tau immunoreactivity.

Nephropathic cystinosis is a rare autosomal recessive storage disorder caused by CTNS gene mutations, leading to autophagy-lysosomal pathway impairment and cystine crystals accumulation. Neurologic involvement is highly variable and includes both neurodevelopmental and neurodegenerative disturbances, as well as focal neurologic deficits. By presenting longitudinal data of a 28-year-old patient with a large infratentorial lesion, we summarized the pathology, clinical and imaging features of neurological involvement in cystinosis patients.

The Molecular Diagnosis Might Be Clinically Useful in Discrepant Kidney Allograft Biopsy Findings: An Analysis of Clinical Outcomes.

Background: The Molecular Microscope Diagnostic System (MMDx) may overcome histology shortcomings. Previous studies have simply examined discrepant findings but have not attempted to determine clinical endpoints. To measure performance, clinical outcomes are strongly required.

Incidence of new onset glomerulonephritis after SARS-CoV-2 mRNA vaccination is not increased.

Numerous cases of glomerulonephritis manifesting shortly after SARS-CoV-2 vaccination have been reported, but causality remains unproven. Here, we studied the association between mRNA-based SARS-CoV-2 vaccination and new-onset glomerulonephritis using a nationwide retrospective cohort and a case-cohort design. Data from all Swiss pathology institutes processing native kidney biopsies served to calculate incidence of IgA nephropathy, pauci-immune necrotizing glomerulonephritis, minimal change disease, and membranous nephropathy in the adult Swiss population.

Clinical spectrum of gross haematuria following SARS-CoV-2 vaccination with mRNA vaccines.

Background: Novel messenger RNA (mRNA)-based vaccines play an important role in current vaccination campaigns against SARS-CoV-2. They are highly efficacious and generally well tolerated. Vaccination in patients with immune-mediated kidney diseases is recommended.

Eosinophilic solid and cystic renal cell carcinoma and renal cell carcinomas with TFEB alterations: a comparative study.

Aims: Eosinophilic solid and cystic renal cell carcinoma (ESC RCC) is a recently described renal tumour entity with frequent cytokeratin (CK)20 positivity, commonly harbouring TSC mutations. In contrast, frequency of CK20 expression and presence of TSC mutations are unclear in TFEB-amplified RCC and TFEB-translocated RCC, which frequently express Melan A. Herein, we provide a comparative analysis of six ESC RCC with four TFEB-amplified/translocated RCC.

Successful Induction of Specific Immunological Tolerance by Combined Kidney and Hematopoietic Stem Cell Transplantation in HLA-Identical Siblings.

Induction of immunological tolerance has been the holy grail of transplantation immunology for decades. The only successful approach to achieve it in patients has been a combined kidney and hematopoietic stem cell transplantation from an HLA-matched or -mismatched living donor. Here, we report the first three patients in Europe included in a clinical trial aiming at the induction of tolerance by mixed lymphohematopoietic chimerism after kidney transplantation.

The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth.

Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic "type 1 versus type 2" classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth.

Granulomatous lung disease and immune reconstitution inflammatory syndrome in Whipple's disease.

We present the case of a 70-year-old woman with a history of seronegative arthritis, recurrent pleural effusion and weight loss. A prior lung biopsy had revealed non-caseating epithelioid cell granulomas without evidence for microbial organisms on special stains. Intestinal biopsy findings where suspicious for Whipple's disease, which was confirmed by PCR testing, both on the intestinal and retrospectively on the lung tissue.

Novel morphological and genetic features of fumarate hydratase deficient renal cell carcinoma in HLRCC syndrome patients with a tailored therapeutic approach.

The hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is defined by germline mutations in the fumarate hydratase (FH) gene and associated with leiomyomas and aggressive renal cell carcinomas with FH deficiency. Here, we comprehensively characterize two new patients with HLRCC syndrome on a morphological, immunohistochemical and genetic level. The patients developed aggressive HLRCC syndrome-associated RCCs, uterine leiomyomas and dermal leiomyomas.

Inter-observer reproducibility of classical lobular neoplasia (B3 lesions) in preoperative breast biopsies: a study of the Swiss Working Group of breast and gynecopathologists.

Purpose: Classical type of lobular neoplasia (LN) spans a spectrum of disease, including atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), classical lobular neoplasia (LN), and the three-tiered classification of lobular intraepithelial neoplasia (LIN-1, -2, -3). This study addressed inter-observer variability of classical lobular neoplasias (LN) (B3 lesions) in preoperative breast biopsies among breast and gynecopathologists METHODS: A retrospective, observational, cross-sectional study was conducted. 40 preoperative digital images of breast core/vacuum biopsies were analyzed by eight experienced breast- and gynecopathologists.

Spiradenocarcinoma: A Comprehensive Data Review.

Introduction: Spiradenocarcinomas (SCs) are rare and potentially aggressive skin adnexal tumors. Optimal treatment has not yet been established. Experiences with this carcinoma are mostly presented in case reports and few case series.

Alveolar echinococcosis of the right adrenal gland: a case report and review of the literature.

Background: Extrahepatic manifestations of Echinococcus multilocularis are very rare, especially in the adrenal glands. To the best of our knowledge, only seven cases of adrenal alveolar echinococcosis have been reported, all from the Far East. All of these occurred exclusively in the right adrenal gland.

An unusual case of mediastinal mass and bilateral nodules.

A 23-year-old woman presented with a mediastinal paraganglioma and multiple pulmonary chondromas following antral gastric resection for gastrointestinal stromal tumor. These tumors form the Carney triad, a rare disorder of unknown genetic background. First described in 1977, approximately 120 cases have been documented in the literature.

Preinvasive colorectal lesion transcriptomes correlate with endoscopic morphology (polypoid vs. nonpolypoid).

Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ∼30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns.