Variations in germ cell tumor histology by age and implications for cancer-specific survival among pediatric and adult males: A population-based study.

PURPOSE: Few studies have quantified differences in histology and implications for survival between male children and adults with germ cell tumors (GCT). We evaluated these differences and associations with cancer-specific survival (CSS) using Surveillance, Epidemiology, and End Results (SEER) cancer registries. METHODS: SEER (1988-2016) was used to identify male patients 0 to 40 years of age diagnosed with seminoma and nonseminomatous GCT (NSGCT). Demographic and tumor characteristics were tabulated with histology distributions compared by age group (0-4, 12-18, 19-40 years old). CSS was evaluated in multivariable Cox proportional hazards regression models. RESULTS: Among 27,204 patients identified, 1,538 (5.7%) were pediatric (0-18 years). Seminoma (54.3%) predominated in adult patients (ages 19-40). Among 0 to 4 years-old, yolk sac tumor (71.2%) and teratoma (21.5%) were most common. Mixed GCT (52.7%) was most prevalent among 12 to 18 years-old with seminoma, embryonal, and teratoma occurring in 12 to 15% each. Relative to pediatric patients, adult patients had similar CSS for seminoma but worse CSS for NSGCT on Kaplan-Meier curves with 9 years mean follow-up. Choriocarcinoma and yolk sac tumors carried the worst prognosis relative to seminoma for both children (HR 5.7 and HR 11.1, respectively, both P < 0.01) and adults (HR 4.6 and HR 4.6, respectively, both P < 0.01) adjusted for stage. CONCLUSION: Histology of GCTs vary by age with yolk sac tumors and teratoma predominating for male patients 0 to 4 years, mixed GCT for 12 to 18 years, and seminoma for 19 to 40 years. Pediatric patients with NSGCT had higher CSS than their adult counterparts. Mixed GCT represented an increasing proportion of GCT over the study period. Age, stage, and histology impact CSS in both pediatric and adult populations.

Expression of L1 Cell Adhesion Molecule, a Nephronal Principal Cell Marker, in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA's potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell-collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.

Localized Urinary Bladder Amyloidosis as Urothelial Cancer Mimicker.

CONTEXT.­: Localized amyloidosis of the bladder is rare and often mimics bladder malignancy. It is typically associated with the extracellular deposition of monoclonal light chains, either κ or λ. The cause is unknown, but it is thought to be due to chronic inflammation/cystitis. OBJECTIVE.­: To highlight the importance of localized urinary bladder amyloidosis as a rare mimicker of urothelial malignancy and elucidate its clinical, histopathologic, and cytopathologic manifestations. DESIGN.­: Cases of urinary bladder amyloidosis diagnosed during 2000-2023 were retrieved retrospectively from pathology archives. Electronic medical records, including cystoscopy findings and pathology slides including Congo red stain, were reviewed. RESULTS.­: Here we present 6 patients with localized urinary bladder amyloidosis. Four of the 6 patients were women, with ages ranging from 46 to 69 years, and a mean age of 58 years. Five of 6 patients presented with hematuria, while in 1 patient, bladder amyloidosis was discovered incidentally. Cystoscopy findings invariably were concerning for malignancy, with raised erythema in 5 patients and fungating mass protruding into the bladder lumen in 1 patient. Bladder biopsies and urine cytology were negative for malignancy in all cases. Congo red-positive amyloid deposits involved lamina propria with sparing of the detrusor muscle. In 5 cases, the deposits were typed as derived from the λ light chain, whereas no information was available for 1 patient. Subsequent clinical workup ruled out systemic amyloidosis. CONCLUSIONS.­: These cases of urinary bladder amyloidosis highlight the importance of considering rare amyloidosis in the differential diagnosis of hematuria and cystoscopy with a lesion mimicking malignancy.

Grade group 4 prostate cancer without intraductal carcinoma on biopsy is more likely to be downgraded on prostatectomy than with intraductal carcinoma.

In this study, we investigated the association between intraductal carcinoma of the prostate (IDCP) along with several histopathological features on prostate biopsy and downgrading of grade group 4 (GG4) prostate cancer (PCa) in patients with the highest grade tumor of GG4 PCa in at least one core. A total of 29 cases had the highest grade tumor of GG4 PCa and radical prostatectomy performed between 2016 and 2021. IDCP was detected in 11 out of 29 cases on biopsy. The cases without IDCP were more likely to be downgraded on prostatectomy than with IDCP, with statistical significance (88.9% vs 36.4%, p = 0.003). The proportions of the highest-grade tumors by length and cores involved, average numbers of PCa-positive cores, and mean patient's age did not differ between cases that were downgraded and not downgraded at prostatectomy. Our results suggest that the absence of IDCP on biopsy could be a predictor of downgrading at prostatectomy for patients with the highest grade tumor of GG4 PCa.

Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients-A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT.

Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187 , which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors.

Incidental Discovery of Hepatocellular Carcinoma on 18F-PSMA PET CT Performed for Prostate Cancer Reassessment.

Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been approved by the Food and Drug Administration (FDA) to identify prostate cancer in the setting of biochemical recurrence but can also identify other malignancies. 18F-PSMA PET has not been studied as a potential tool for hepatocellular carcinoma (HCC). We describe the case of a 76-year-old male with a rising prostate-specific antigen (PSA) after definitive prostate cancer treatment and no prior liver pathology who was incidentally found to have HCC on 18F-PSMA PET.

Kidney Biopsy Un-masquerading Plasma Cell Leukemia Diagnosed as Acute Myeloid Leukemia: An Unusual Clinical Experience.

Plasma cell leukemia (PCL) is a rare aggressive variant of plasma cell myeloma. The differential diagnosis of PCL includes multiple myeloma (MM), other leukemias, and lymphomas with abnormal cells circulating in the peripheral blood. In addition, infectious or autoimmune diseases can cause reactive polyclonal plasmacytosis, which could confuse us with PCL occasionally. Sometimes, blastoid morphology can cause confusion in diagnosis, and immunohistochemistry is needed to differentiate PCL from other forms of leukemias and lymphomas. Here, we present a rare case of PCL diagnosed as acute myeloid leukemia (AML) with kidney biopsy establishing the correct diagnosis.

Localized Amyloidosis of the Sphenoid Sinus: A Case Report and a Descriptive Literature Review.

Amyloidosis is the process of extracellular deposition of protein fibrils and manifests pathologically as a systemic or localized process. Localized amyloidosis of the head and neck is uncommon, and involvement of the sphenoid sinus is exceedingly rare. We describe a case of localized amyloidosis isolated from the sphenoid sinus. A descriptive literature search was conducted to highlight presentation, management, and outcomes related to this pathology. Our patient was a 65-year-old male who presented to our clinic with nasal congestion and an incidental finding of a large expansile mass within the sphenoid sinuses. The mass was seen to displace the pituitary gland, and thus a multidisciplinary care approach ensued. The mass was removed via a transnasal endoscopic approach. Pathology revealed fibrocollagenous tissue with calcifications that were positive on Congo red staining. The patient underwent further workup to rule out systemic involvement, which was unremarkable. Based on the findings of his workup, he was ultimately diagnosed with localized amyloidosis. A comprehensive review of the literature revealed 25 other reported cases of localized amyloidosis within the sinonasal region, with only one other case of isolated sphenoid sinus disease. Common presenting symptoms are nonspecific and may mimic other, more frequently seen regional pathologies, including nasal obstruction, rhinorrhea, and epistaxis. The treatment for localized disease is surgical resection. While localized amyloidosis within the sinonasal region is rare, it is important to recognize, work up, and treat it appropriately. A multidisciplinary team approach is necessary for appropriate diagnosis and management, and these patients should be followed closely after treatment.

Sjögren's Syndrome Overlap With Lupus Nephritis: A Case Report and Literature Review of a Rare Entity.

Overlap syndrome is a connective tissue disorder that satisfies the diagnostic criteria for at least two well-known autoimmune diseases. In this report, we describe a rare case of lupus overlap in an elderly woman with primary Sjögren's syndrome who presented with features of nephritic-nephrotic syndrome and renal biopsy results typical of lupus nephritis combined with multiple positive autoantibodies. The kidney biopsy results were assigned the highest weightage based on the revised 2019 systemic lupus erythematosus (SLE) classification criteria developed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). The patient's condition significantly improved after appropriate immunosuppressive therapy was initiated. With the revised ACR/EULAR-2019 criteria, we anticipate that more SLE patients with typical lupus nephritis biopsy findings will be diagnosed accurately.

Adenovirus-Associated Acute Interstitial Nephritis With Graft Survival and Novel Follow-Up Biopsy Findings Including Karyomegaly: A Case Series.

Adenoviral infections in post-transplant patients have been described in multiple organ systems, most classically the lung, liver, and alimentary tract. In the genitourinary tract, hemorrhagic cystitis is most frequently observed. Clinically apparent renal involvement with adenovirus is rare, and adenovirus-associated interstitial nephritis (AAIN) is an uncommon cause of renal allograft failure. Here, we present three cases of AAIN in patients who, after prompt diagnosis and treatment adjustment, experienced a return of allograft function. All patients were on standard triple therapy with tacrolimus levels within the target range at the time of biopsy. None of the patients had respiratory symptoms, and despite diarrhea, colon biopsies were negative. Only case one had positive adenovirus serology (IgG only) and case three had positive urine; two patients had leukopenia without neutropenia. Renal biopsies showed a characteristic granulomatous tubulocentric mixed lymphocytic and neutrophilic infiltrate. Adenovirus immunohistochemistry (IHC) showed strong staining in the tubular epithelium (nuclear and cytoplasmic) while staining for polyomavirus was negative. A follow-up biopsy two months after the diagnosis of AAIN in one patient revealed persistent cytopathic effects with negative adenoviral IHC staining while a biopsy at one year in another patient showed glomerular and tubulointerstitial scarring. AAIN is an uncommon but important etiology to consider in cases of acute renal allograft dysfunction. Although the presenting symptoms for AAIN are nonspecific, hematuria is frequently noted. Adenovirus IHC should be considered in cases with granulomatous inflammation associated with necrosis and mixed inflammatory infiltrate. As demonstrated in this single-institution case series, prompt diagnosis can result in the preservation of the renal allograft. Lasting cytopathic effects after adenoviral infection should also be considered in patients with a history, or potential history, of AAIN.

Subarachnoid Hemorrhage in Autoimmune Vasculitis: A Rare Presentation of Systemic Lupus Erythematosus-Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis Overlap Syndrome.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE), though they share similar clinical characteristics, are distinguishable based on specific characteristics. The concomitant presentation of SLE and AAV as overlap syndrome is rare and makes the diagnosis challenging. Here, we describe a rare case of SLE and AAV overlaps presenting with hemorrhagic stroke as initial presentation, which has been reported only once before. The presence of several positive autoantibodies made the diagnosis challenging, but a kidney biopsy provided the definitive diagnosis and aided in initiating immunosuppressive therapy. The patient did not respond to standard initial surgical measures to lower elevated intracranial pressure and showed significant improvement to immunosuppressive therapy proving the temporal relationship. The authors of this case study aim to highlight the importance of considering SLE-AAV overlap in patients presenting with features similar to those described in the case report and intervening early, as delays in diagnosis can be fatal.

Novel Histopathologic and Ultrastructural Findings in Renal Allografts From Patients With Size and Age Mismatches: A Case Series.

While reports on the long-term pathology in mismatched allografts have been focused on the donor and recipient body surface area, evidence is emerging to support donor-recipient age difference as an additional prognostic factor. Most reports are based on pediatric recipients receiving older/bigger allografts. Here, we describe three cases with age mismatch including two cases of adult patients receiving pediatric allografts and a third case of a younger patient receiving an allograft from an older donor exhibiting findings not described in extant literature. Each of these cases exhibits unique changes seen in mismatched donor-recipient size/age post-transplant pathology. These non-rejection changes should be suspected in cases of donor-recipient size/age mismatch. In cases of allograft function decline, a full biopsy workup, including electron microscopy, should be considered.

Adverse reaction to metal debris with accompanying gout and amyloid deposits in hip arthroplasty.

Adverse reaction to metal debris (ARMD) is a known complication of metal-on-metal hip arthroplasty. There has been one previously reported case of ARMD with concomitant gout in the setting of a hip arthroplasty. We report a case of ARMD with accompanying monosodium urate crystals as well as amyloid deposition in the hip of a patient who had undergone a metal-on-metal hip arthroplasty. This is the only published case to date of these 3 conditions co-existing, although it is possible that the incidence is higher since these require special diagnostic tests that are not routinely performed. It is postulated that these entities are biochemically associated with each other rather than being purely coincidental.

The rising incidence of ductal adenocarcinoma and intraductal carcinoma of the prostate: Diagnostic accuracy of biopsy, MRI-visibility, and outcomes.

INTRODUCTION: Ductal adenocarcinoma (DA) and intraductal carcinoma (IDC) of the prostate are associated with higher stage disease at radical prostatectomy (RP). We evaluated diagnostic accuracy of biopsy, MRI-visibility, and outcomes for patients undergoing RP with DA/IDC histology compared to pure acinar adenocarcinoma (AA) of the prostate. MATERIALS AND METHODS: A retrospective cohort study of men receiving RP between 2014 and 2021 revealing AA, DA, or IDC on final pathology was conducted. Multivariable logistic regression and Cox proportional hazards regression models were employed. RESULTS: A total of 609 patients were included with 103 found to have DA/IDC. Patients with DA/IDC were older and had higher PSA, biopsy grade group (GG), RP GG, and other pathologic findings (extraprostatic extension, lymphovascular invasion, perineural invasion, pN stage) compared to AA patients (all P < 0.05). On multivariable analysis, higher age, RP GG, and pT3a were associated with DA/IDC on RP (all P < 0.05). Sensitivity and specificity of biopsy compared to RP for diagnosis of DA/IDC was 29.1% (16.7% DA, 27.8% IDC) and 96.6% (99.3% DA, 96.6% IDC), respectively. In a subset of 281 men receiving MRI, PI-RADS distribution was similar for patients with DA/IDC vs. AA (90.7% vs. 80.7% with PI-RADS 4-5 lesions, P = 0.23) with slightly higher biopsy sensitivity (41.9%). DA/IDC was associated with worse BCR (HR = 1.77, P = 0.02) but not biopsy DA/IDC (P = 0.90). CONCLUSIONS: Sensitivity of prostate biopsy was low for detection of DA/IDC histology at RP. Patients with DA/IDC histology had unfavorable pathologic features at RP and worse BCR. Of patients with DA/IDC at RP, 90.7% were categorized as PI-RADS 4 to 5 on preoperative MRI.

Differentiating Oncocytic Renal Tumors from Chromophobe Renal Cell Carcinoma: Comparison of Peak Early-phase Enhancement Ratio to Clinical Risk Factors and Rater Predictions.

Background: Most surgically resected benign renal tumors are found to be oncocytomas or indolent hybrid oncocytic tumors, which are difficult to differentiate from chromophobe renal cell carcinoma (chRCC) on renal mass biopsy. Both often exhibit CD117+ staining. Objective: To evaluate the ability of the peak early-phase enhancement ratio (PEER) to distinguish oncocytomas from chRCC and compare its discrimination to traditional clinical risk factors and blinded clinical raters. Design setting and participants: This was a diagnostic case-control study of patients (2006-2020) with oncocytoma or chRCC according to surgical pathology. Intervention: Partial or radical nephrectomy. Outcome measurements and statistical analysis: Three clinical raters blinded to histology measured the PEER and the presence of stellate scar and predicted the final histology for each tumor. Averaged and individual PEER values were compared to surgical pathology and assessed for interobserver variability. Subanalyses were conducted for patients with confirmed CD117+ status. Results and limitations: For the 76 patients identified, PEER was higher among the 32 (42.1%) oncocytomas than among the 44 (57.9%) chRCCs (median 0.81 vs 0.43; p < 0.001), with high correlation across raters (correlation coefficients ≥0.85). A PEER cutoff of <0.60 was strongly associated with identification of chRCC (OR 95.7 (95% CI 19.9-460.8), p < 0.001). In the overall and CD117+ cohorts, sensitivity was 93.2% and 97.0%, the negative predictive value was 90.3% and 95.5%, and the area under the receiver operating characteristic curve (AUC) on multivariable modeling was 95.0% and 98.1%, respectively. PEER outperformed models with clinical risk factors alone (AUC 70.4%) and histology predictions by three raters (AUC 51.6%, 62.5%, and 63.1%). Limitations include reliance on surgical pathology and inclusion of a mix of early contrast-enhanced phases. Conclusions: PEER reliably differentiated benign renal oncocytomas and indolent hybrid tumors from malignant chRCC with excellent diagnostic performance. A diagnostic pathway with biopsy, CD117 staining, and PEER deserves further study to potentially avoid unnecessary surgery for oncocytic renal tumors. Patient summary: We assessed a measurement called PEER on computed tomography (CT) scans and found higher values for benign and lower values for malignant kidney masses, so we were able to tell these apart. PEER was reliable for identifying tumors with positive staining for the CD117 protein biomarker as well as in the overall patient group. Our results show that PEER could be considered for use with biopsy and CD117 staining to potentially avoid unnecessary surgery for benign kidney masses.

Current Understanding of Systemic Amyloidosis and Underlying Disease Mechanisms.

Amyloidosis is a group of diverse disorders caused by misfolded proteins that aggregate into insoluble fibrils and ultimately cause organ damage. In medical practice, amyloidosis classification is based on the amyloid precursor protein type, of which amyloid immunoglobulin light chain, amyloid transthyretin, amyloid leukocyte chemotactic factor 2, and amyloid derived from serum amyloid A protein are the most common. Distinct mechanisms appear to be predominantly operational in the pathogenesis of particular types of amyloidosis, including increased protein precursor synthesis, somatic or germ line mutations, and inherent instability in the precursor protein in its wild form. An increased supply of misfolded proteins and/or a decreased capacity of the protein quality control systems can result in an imbalance that leads to increased circulation of misfolded proteins. Although the detection of mature fibrils is the basis for diagnosis of amyloidosis, a growing body of evidence has implicated the prefibrillar species as proteotoxic and key contributors to the development of the disease.

Percentage of sarcomatoid histology is associated with survival in renal cell carcinoma: Stratification and implications by clinical metastatic stage.

PURPOSE: Sarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival. MATERIALS AND METHODS: Patients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005-2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: One hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (P = 0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, P = 0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03-1.23], P = 0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27-6.47], P = 0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH). CONCLUSIONS: SH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance.

Tissue biopsy for the diagnosis of amyloidosis: experience from some centres.

A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.

Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/- mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2-/- tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/- heterozygous (>60 weeks) mice that carry spontaneous Tsc2-/- tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

Acute Kidney Injury Associated With Semaglutide.

Case reports of acute kidney injury in patients taking the glucagon-like peptide 1 (GLP-1) receptor agonists exenatide and liraglutide have been reported. We report 2 patients with chronic kidney disease due to diabetic kidney disease who experienced rapid worsening of kidney function and increased proteinuria after being prescribed the GLP-1 receptor agonist semaglutide. In 1 patient, kidney biopsy showed advanced diffuse and nodular glomerulosclerosis accompanied by interstitial lymphoplasmacytic and eosinophilic infiltrate and evidence of acute tubular injury. At this time, the long-term outcomes of patients who experience acute kidney injury associated with GLP-1 receptor agonists is not known. We recommend that caution be used with these agents in patients with moderate to severe chronic kidney disease due to limited kidney reserve in the event of an adverse kidney event. Because most adverse kidney events have occurred in patients who experience adverse gastrointestinal symptoms, such patients should have laboratory tests and discontinuation of the medication if there is acute worsening of kidney function.