Patient-derived organoids (PDOs) offer a powerful in vitro platform to model cancer biology, investigate therapeutic responses, and personalize treatment strategies. Here, we describe a comprehensive and reproducible protocol for establishing 3-dimensional (3D) organoid cultures from surgically resected triple-negative breast cancer (TNBC) samples. Fresh TNBC surgical tissues were processed using a standardized enzymatic and mechanical dissociation protocol followed by 3D culture in Matrigel. Organoids were expanded, cryopreserved, and characterized through histology, immunohistochemistry (IHC), and whole-exome sequencing (WES). Immunophenotypic and genomic concordance was assessed between PDOs and their paired tumors. Organoids were successfully established from resected TNBC tissues, displaying histologic, immunohistochemical, and genomic fidelity supporting high-throughput and personalized research applications.

Background:Differentiating benign from malignant peripheral pulmonary lesions (PPLs) remains a clinical challenge, especially in resource-limited settings. While computed tomography is the standard imaging modality, it involves radiation exposure and often lacks specificity. Shear Wave Elastography (SWE) is a non-invasive ultrasound technique that quantifies tissue stiffness and may aid in the evaluation of PPLs. Methods:In this prospective observational study, 42 patients with peripheral pulmonary lesions underwent transthoracic SWE prior to histopathological evaluation. Elastography values were compared between benign and malignant lesions. Statistical analysis included ROC curve assessment, logistic regression, and correlation with histopathological and microbiological outcomes. Results:Of the 42 patients, 64.3% had malignant and 35.7% had benign lesions. The mean SWE value for malignant lesions was significantly higher (6.82 ± 2.27 kPa) than for benign lesions (3.72 ± 2.23 kPa; p <0.001). The AUROC for mean SWE values in predicting malignancy was 0.849 (95% CI: 0.713-0.986), demonstrating good diagnostic performance with statistically significant difference (p = <0.001), with a cutoff of ≥4.8 kPa yielding 85% sensitivity and 80% specificity. Squamous cell carcinoma exhibited the highest stiffness among malignancies. Certain benign lesions, particularly tuberculosis, showed elevated stiffness, resulting in false positives. Logistic regression identified mean SWE as an independent predictor of malignancy (OR = 2.11, p = 0.030). Conclusion:Transthoracic SWE is a non-invasive, radiation free and promising tool for evaluating PPLs, offering good diagnostic accuracy in distinguishing malignant from benign lesions. It holds particular promise in settings where access to advanced imaging or biopsy is limited, and may assist in triaging patients for early tissue diagnosis.

Claudin-low breast cancers (BCs), representing approximately 1.5–14

HER2-overexpressing (3+) breast cancer exhibits distinct clinicopathological characteristics compared to HER2 1+ and 2+ tumors; however, differences in their molecular features remain poorly defined. This study aimed to investigate clinicopathologic and somatic alterations in breast tumors stratified by HER2 status. Ninety breast cancer patients were stratified by HER2 expression (1+, 2+, 3+) using immunohistochemistry and confirmed by FISH. For each patient, paired diagnostic biopsies and post-neoadjuvant chemotherapy (NACT) residual tumors were analyzed. Targeted next-generation sequencing (NGS) was performed on 34 paired samples, and shortlisted variants were validated by digital droplet PCR (ddPCR) in 90 cases. Among the 90 paired samples, 40 were HER2-high, and 50 were HER2-low/TNBC. HER2-high tumors presented with a larger mean size (3.34 cm vs. 2.29 cm) but lower lymph-node metastasis (40

BACKGROUND:Post-mortem tissue sampling can help determine the cause of death, particularly in resource-limited settings. We conducted a retrospective audit of minimally invasive autopsies (MIA) performed in a respiratory intensive care unit. METHODS:Lung biopsies were obtained using either a core biopsy needle (CBN) or through a small thoracic incision at the fourth intercostal space (open incision method [OIM]). We performed a kidney or liver biopsy using a CBN with ultrasound guidance. The final cause of death, ascertained by a multidisciplinary team, served as the reference standard. The primary objective was to assess biopsy yield and the frequency of diagnostic revision based on histopathological findings. RESULTS:One hundred and sixteen patients underwent MIA. Lung biopsies were done in all cases (66 [56.9%] by CBN and 50 [43.1%] by OIM). Kidney and liver were biopsied in less than 10% of cases. Twelve biopsies (10.3%) were non-representative and excluded from further analysis. The overall biopsy yield was 74%. Pathological findings led to a change in the final diagnosis in three cases (2.9%). Infections aetiologies were most common, including bacterial pneumonia (24, [23.1%]), fungal pneumonia (8, [7.7%]), and tuberculosis (2, [1.9%]). Malignancy was identified in 8 (7.7%) cases. The diagnostic yield was significantly higher with OIM than with CBN (87.5% vs. 62.5%, P = 0.004). Agreement between clinical and pathological diagnoses was fair (kappa = 0.41, P < 0.001). CONCLUSION:MIA achieved a 74% diagnostic yield with fair agreement with the MDT-determined cause of death. OIM provided a superior yield compared to CBN and may be preferable where feasible.

Background Neoangiogenesis, a key feature of tumor progression, results in increased blood flow (BF), blood volume (BV), and vascular permeability. Dynamic volume perfusion computed tomography (dVPCT) complements conventional morphological assessment by providing valuable insights into tumor vascularity, treatment response, and prognosis. Emerging evidence shows strong correlations between dVPCT parameters, microvessel density, and angiogenic markers, underscoring its potential utility in the comprehensive management of lung cancer. Objectives The aim of this study was to assess the role of dVPCT in the noninvasive evaluation of lung cancer by correlating perfusion parameters with histopathology. Materials and Methods A prospective study was conducted on 40 patients with clinically suspected lung cancer who met the inclusion criteria. All participants underwent dVPCT using a standardized protocol, Adaptive 4D Spiral acquisition followed by postprocessing based on the deconvolution method. Perfusion parameters, including BV, BF, mean transit time (MTT), and flow extraction product (FEP), were analyzed and compared across different histological subtypes. A p-value of less than 0.05 was considered statistically significant. Results Among 40 lung cancer patients, dVPCT revealed significant differences in perfusion parameters across histological subtypes. Adenocarcinoma (AC) demonstrated the highest BV (40.62 +/- 21.42 mL/100 mL) and FEP (21.85 +/- 4.91 mL/100 g/min), both significantly higher than in nonAC groups (p = 0.013 and p = 0.002, respectively). FEP showed the best diagnostic performance with 90% sensitivity and 80% specificity in differentiating AC. BF and MTT did not show statistically significant variation among subtypes. Conclusion dVPCT shows potential as a noninvasive tool for differentiating lung cancer subtypes, with BV and FEP offering significant diagnostic value.

Fungal keratitis (FK) is a serious corneal infection leading to blindness. The present study aims to develop a duplex ddPCR for the detection of Aspergillus sp. and Fusarium sp. causing FK and also to enhance the diagnostic accuracy by evaluating the sensitivity of ddPCR in comparison to qPCR. This Prospective, multicentric study was conducted from November 2019 to August 2021, including three healthcare facilities across India. All patients suspected with FK were included in the study. A part of the collected corneal samples was used for routine microbiological workup and another part of the sample was used for the standardization and validation of ddPCR. A total of 42 corneal buttons were used for standardisation. Aspergillus primer concentration of 750 nM showed highest sensitivity of 81.48% with 93.33% specificity at ct-value 14.05 while 900 nM primer concentration was best for Fusarium with 80% sensitivity and 96.3% specificity at ct-value 83.65. Probe concentrations for both Aspergillus and Fusarium were 250mM. Validation cohort included 74 corneal samples, Aspergillus ddPCR demonstrated 84.21% sensitivity with 94.64% specificity while Fusarium ddPCR had 75% sensitivity with a specificity of 96.3%. The comparative analysis demonstrated an improvement in diagnostic performance by ddPCR for both Aspergillus and Fusarium compared to recently reported genus-specific real-time PCR. The ddPCR noticeably enhanced the diagnostic performance for both Aspergillus and Fusarium FK in comparison to the genus-specific real-time PCR. Thus, ddPCR can serve as a rapid technique holding a challenge over conventional and qPCR for FK diagnosis.

Worst pattern of invasion (WPOI) has been evaluated in many single-institute cohorts. Our goal was to perform a large multicentre evaluation of WPOI as a prognostic marker in oral squamous cell carcinoma (OSCC). Retrospective pathology data was collated from 14 institutions and compared with clinical outcome in 1374 OSCC patients with upfront curative resection. Most cases were of oral tongue (n = 645, 47%); T2 (33%) and N0 (59%). WPOI 1-3 frequency was 29.4%, WPOI 4 47% and WPOI 5 22%. On univariable analysis, the 3-year disease free survival (DFS) was 54.2% for WPOI 5 vs. 69.7% for WPOI 1-4 (p < 0.001). The locoregional control (LRC) was 68.9% vs 79.2% (p = 0.001), and overall survival (OS) 68.4% vs 83.8% (p < 0.001). On multivariable Cox-regression in the entire cohort, WPOI 4 or 5 was strongly correlated with other known poor prognostic factors and not an independent predictor of OS (HR 1.10, 95% CI 0.92-1.52), LRC or DFS. However, in early-stage (pT1-2 N0) patients treated with surgery alone without adjuvant radiotherapy, WPOI 5 was a robust independent predictor of DFS (HR 4.36, 95% CI 1.54-12.32, p = 0.006), OS (HR 3.69, 95% CI 1.23-11.1, p = 0.020) and LRC (HR 3.52, 95% CI 2.13-5.82, p <0.001) after applying inverse probability weighting to correct for selection bias. Furthermore, in the entire cohort of early-stage patients, interaction modeling showed that adjuvant radiotherapy significantly reduces the risk for both DFS and LRC for those with WPOI-5 (Interaction p = 0.002). Therefore, it may act as a predictive biomarker for the benefit of adjuvant radiotherapy. The prognostic and predictive role of WPOI-5 should be validated in prospective trials.

Solitary fibrous tumours (SFTs) are a rare group of neoplasms of mesenchymal origin. We report a case of a 47-year-old male who was found to have an intensely enhancing large mass in the anterior mediastinum on contrast-enhanced computed tomography which was proved to be a SFT on histopathology.

BACKGROUND:Pulmonary mucormycosis (PM) imaging has been characterised primarily in patients with hematologic malignancies. Imaging patterns may differ in diabetes mellitus-associated PM (DAPM), the most common risk factor globally, due to different immunologic profiles and disease progression. The impact of glycemic control on CT findings in DAPM is unknown. METHODS:We retrospectively analysed chest CT scans of patients with PM, compared DAPM with PM in other risk factors (PMOR), and evaluated imaging features across glycated haemoglobin (HbA1c) categories. The secondary objective was to determine associations between imaging features and mortality in DAPM. Imaging patterns recorded by two radiologists were compared between study groups, and multivariable logistic regression analysis of mortality was performed. RESULTS:Among 193 patients (161 DAPM, 32 PMOR), consolidation (97%) and cavitation (84%) were the most frequent. DAPM presented significantly later (median 30 vs. 7 days; P < 0.001) and showed distinct features: smaller nodules (62%, <10 mm) with centrilobular distribution (37.4%), while PMOR had larger nodules (10-30 mm, 55.0%) with random distribution (75.0%). Lymphadenopathy was more common in DAPM (26.0% vs. 9.4%, P = 0.043). Among DAPM, Bird's nest sign increased with HbA1c severity: 7.7% (HbA1c ≤7%), 33.3% (HbA1c 7-9%), and 43.3% (HbA1c>9%), P = 0.030. Overall, 12-week mortality was 47.9%. Although the reversed halo sign and bird's nest sign were associated with mortality on univariable analysis, neither was significant after adjusting for clinical factors. CONCLUSION:DAPM presents later and exhibits distinct imaging features compared to PMOR. Bird's nest sign is more frequent with HbA1c >9%. No imaging features were independently associated with mortality.

Background: Diffuse Large B-cell Lymphoma (DLBCL) is a biologically heterogeneous subtype of non-Hodgkin's lymphoma (NHL), accounting for 30-40% of cases worldwide. Despite the incorporation of rituximab into standard chemo-immunotherapy regimen, approximately one-third of patients present with relapsed or refractory disease, implicating the need for improved prognostic markers and therapeutic targets. Gene expression profiling successfully classified DLBCL into Germinal Center B-cell-like (GCB) and non-GCB subtypes, which differ in genetic alterations, response to therapy, and clinical outcome. While intrinsic tumor biology has been extensively studied, the contribution of the tumor microenvironment (TME) to disease progression and therapeutic resistance still remains incompletely understood. Methods: In this study, we investigated the mutational landscape of stromal-related genes in DLBCL and evaluated their impact on gene expression, downstream signaling pathways, and tumor progression. Results: A total of 176 DLBCL patients were screened, of which 113 were enrolled based on availability of complete clinical data. The cohort demonstrated male predominance (male:female ratio: 2.1:1), advanced disease stage in 72.6% of patients, and elevated serum lactate dehydrogenase levels in 57.5%. Based on immunohistochemistry, 43.4% cases were classified as GCB-DLBCL and 56.6% as non-GCB DLBCL. Although the International Prognostic Index (IPI) retained prognostic significance for event-free survival (EFS) and overall survival (OS), considerable heterogeneity was observed within similar risk groups. Whole-exome sequencing (WES) uncovered recurrent somatic mutations in key oncogenic and epigenetic regulators, including TNFAIP3, NFIB, NOTCH1, TSC2, EZH2, EP300, KMT2D, and B2M, with subtype-specific distribution. Pathway enrichment analysis implicated role of Notch, Wnt, mTOR, JAK-STAT, TGF-β, and antigen-presentation pathways. Comprehensive WES analysis identified multiple novel mutations in genes associated with the stromal/extracellular matrix with distinct patterns in GCB and non-GCB DLBCL, accompanied by concordant alterations in gene expression profiles, suggesting functional relevance within the TME. Functional validation through primary cell culture demonstrated significantly elevated Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) cytokines in co-cultures containing both neoplastic cells and stromal components, underscoring the role of TME in DLBCL progression. Conclusions: Taken together, this study provides novel insights into stromal mutational signatures and cytokine-mediated tumor-stroma interactions, offering potential prognostic biomarkers and therapeutic targets for the improved management of DLBCL.

OBJECTIVES:Bone marrow involvement (BMI) upstages lymphoma and influences prognosis and treatment. Conventional bone marrow trephine biopsy (BMTB) may miss patchy or extrapelvic disease. This study compared the diagnostic performance of automated-robotic-arm (ARA)-assisted 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT)-guided bone marrow biopsy with BMTB in treatment-naive lymphoma. METHODS:In this prospective single-centre study, 169 treatment-naive lymphoma patients underwent baseline 18 F-FDG PET/CT and bilateral posterior iliac crest BMTB. Among these, 44 patients with focal FDG-avid marrow lesions (unifocal or multifocal) underwent ARA-assisted PET/CT-guided bone marrow biopsy. Histopathological findings from PET/CT-guided biopsy and BMTB were used to establish the final diagnosis of BMI. Diagnostic performance parameters were calculated with 95% confidence intervals (CIs) using Wilson score method. Comparisons were performed using Fisher's exact test. RESULTS:Of the 44 patients with focal FDG-avid marrow lesions, 40 had lymphomatous BMI on final diagnosis. PET/CT-guided biopsy yielded 37 true positives, four true negatives, and three false-negatives, with no false-positive. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 92.5% (95% CI: 80.1-97.4%), 100% (95% CI: 51.0-100.0%), 100% (95% CI: 90.6-100.0%), 57.1% (95% CI: 25.0-84.2%), and 93.2% (95% CI: 81.8-97.7%), respectively. Conventional BMTB demonstrated significantly lower sensitivity (52.5%) and accuracy (56.8%) ( P  < 0.001). CONCLUSION:ARA-assisted PET/CT-guided metabolic bone marrow biopsy demonstrates superior sensitivity and accuracy than conventional iliac crest trephine biopsy. It improves detection of lymphomatous BMI, boosts diagnostic confidence and reduces over-staging risk. It may play a selective problem-solving tool for focal FDG-avid marrow lesions.

Background Mucormycosis is a life-threatening invasive fungal infection. Current diagnosis relies on insensitive techniques with prolonged turnaround times, underscoring the need for rapid noninvasive diagnostic tools. The current study aimed to identify the antigens of Rhizopus arrhizus that can facilitate serodiagnosis of mucormycosis and assess their diagnostic potential in patients. Methods This was a 2-stage systematic study combining antigen discovery and clinical validation. Using immunoproteomics, we identified immunoreactive protein spots in R. arrhizus secretory extract, using pooled serum samples from 6 patients with mucormycosis. We performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) to characterize the most reactive spot. Next, we developed an indirect enzyme-linked immunosorbent assay using purified protein and evaluated its diagnostic performance in 92 patients with mucormycosis and 41 controls (22 with other mold infections and 19 with diabetes mellitus alone). Participants were randomly divided 1:1 into derivation and validation cohorts. Receiver operating characteristic curve analysis identified optimal cutoff values. Results Immunoproteomics identified 3 immunoreactive protein spots (70, 45, and 30 kDa) in crude extract. The most reactive 70-kDa spot was identified as Rhizopus-specific glucoamylase (RSG) by LC-MS/MS and confirmed with specific anti-Rhizopus glucoamylase antibody. In the derivation cohort (46 patients with mucormycosis and 11 controls), the area under the receiver operating characteristic curve for anti-RSG immunoglobulin (Ig) G was 0.933. In the validation cohort, anti-RSG IgG achieved 76.1% sensitivity (95% confidence interval, 61.2%-87.4%) and 100% specificity (71.5%-100%). The assay also detected antibodies in 85.1% of culture-negative but microscopy-positive cases and in 87.5% of mixed fungal infection cases. Conclusions RSG is a potential biomarker for diagnosing mucormycosis. Anti-RSG IgG shows strong diagnostic promise and merits prospective multicenter clinical validation.

Background:Phosphatase and tensin homolog (PTEN) is a key tumor suppressor gene that negatively regulates the PI3K/AKT pathway. PTEN deficiency is the most frequent molecular alteration in triple-negative breast cancer (TNBC); however, the relationship between PTEN protein loss and underlying genomic alterations remains incompletely understood. Methods:Fifty TNBC cases were evaluated for PTEN protein expression by immunohistochemistry on tissue microarrays. PTEN hotspot mutations (Exons 1, 5, 7, and 9) were analyzed using Sanger sequencing, whereas copy number alterations were assessed by multiplex ligation-dependent probe amplification (MLPA) assay. PTEN alterations were correlated with clinicopathological characteristics. External validation of PTEN mRNA and protein expression and prognostic significance was performed using publicly available TCGA/CPTAC datasets and Kaplan-Meier plotter. Results:PTEN protein loss was observed in 41/50 TNBC cases (82%), indicating that PTEN deficiency is a frequent event in this subtype. PTEN mutations were detected in six cases (12%) and were confined exclusively to Exon 5, comprising one missense mutation (c.277C>A) and two truncating mutations (c.430del and c.433del). MLPA identified PTEN copy number alterations in four cases (8%), including heterozygous deletions and duplications. No significant association was observed between PTEN protein expression and genomic alterations, highlighting a substantial genotype-phenotype discordance. Analysis of independent public datasets confirmed significantly reduced PTEN mRNA and protein expression in TNBC compared with luminal and HER2-positive breast cancers. Patients with low PTEN expression showed a trend toward shorter overall survival (23.5 vs. 38.9 months), though the difference did not reach statistical significance. Conclusions:PTEN protein loss is highly prevalent in TNBC but is only partially explained by mutations and copy number alterations, suggesting that additional regulatory mechanisms, such as epigenetic or posttranscriptional events, contribute to PTEN inactivation. These findings underscore the biological importance of PTEN deficiency in TNBC and support further investigation of PTEN as a potential prognostic biomarker and therapeutic target.

Metaplastic breast carcinoma (MBC) is a heterogenous group of invasive breast cancer with distinct morphological patterns and negativity for hormone receptors and HER2. The pathogenesis of MBC is unknown but tumour cells exhibit epithelial-mesenchymal transition and breast cancer stem cell-like characteristics. Genomic characterisation of these tumours can lead to identification of targetable mutations which may help in improving the overall treatment outcome. Sixty-seven retrospective cases of MBC were sub-classified morphologically. Cytoplasmic expression of ALDH1 was evaluated using IHC to estimate the stemness. Alteration in PI3K/AKT/PTEN/MAPK pathway was studied using next generation sequencing (n = 47). Histological subtypes were squamous cell carcinoma (n = 25), Metaplastic carcinoma with heterologous mesenchymal differentiation (n = 19), spindle cell carcinoma (n = 19), Fibromatosis like metaplastic carcinoma (n = 3), and Mixed metaplastic carcinoma (n = 1). ALDH1 was positive in 31.3% cases. PI3K was the most frequently altered gene followed by PTEN, TP53 and MAPK1 gene. PI3K alterations were more frequent in Spindle cell carcinoma and squamous carcinoma This study identified high frequency of stem cell marker and targetable genetic alterations in the PI3K signalling pathway. Thus, Inhibitors of the PI3K signalling pathway are ideal candidates for targeted therapy for MBC irrespective of histological subtype.

Bone marrow evaluation is central to diagnosing leukemia, lymphoma, unexplained cytopenias and other hematologic disorders, yet it depends on specialised expertise and remains time-consuming, subjective and prone to interobserver variability. We present the Artificial Intelligence Slide Analysis Platform (AiSAP), a deep learning framework for automated bone marrow cellularity estimation directly from raw whole-slide images (WSIs), trained and validated on an Indian clinical trephine biopsy cohort that is underrepresented in existing automated pipelines. Unlike approaches restricted to cropped or pre-selected patches, AiSAP performs end-to-end WSI tiling, automated marrow region-of-interest extraction and adipocyte segmentation using a dual Mask R-CNN architecture, before computing a case-level cellularity ratio. Across five backbone configurations, average precision ranged from 45.3% to 51.9%, while case-level concordance reached up to a Pearson correlation coefficient of 0.95 and Lin's concordance correlation coefficient of 0.88 (depending on the backbone). These results show that AiSAP achieves expert-level concordance for automated cellularity estimation and represents a promising, generalizable step toward clinical decision support in bone marrow pathology, warranting further multi-institutional validation.

BACKGROUND:American Thoracic Society guidelines suggest serum specific IgG (sIgG) testing targeting potential antigens associated with hypersensitivity pneumonitis (HP). The diagnostic cutoffs of mold-sIgGs remain undefined and their performance based on pre- and post-test probabilities remain untested. METHODS:We conducted a diagnostic test accuracy study using a case-control design. We enrolled subjects with HP (cases), other interstitial lung diseases (ILDs, diseased controls), and healthy controls with/without mold exposure. We measured sIgG against Aspergillus fumigatus, Penicillium chrysogenum, Cladosporium herbarum, and Micropolyspora faeni using an automated, fluorescent enzyme immunoassay. Cutoffs were derived from the 95th percentile values among non-exposed healthy controls for individual sIgGs and Youden's J-statistic for pooled sIgG (sum of four levels). We evaluated the performance characteristics of sIgG levels for HP diagnosis among subjects with ILDs. RESULTS:We included 219 subjects (mean age, 51.4 years; 50.2% women): 105 HP, 64 non-HP ILDs, and 50 healthy controls (25 non-exposed, 25 exposed). Cutoffs (mgA/L) were 33, 22, 34, 8, and 53, for A. fumigatus, P. chrysogenum, C. herbarum, M. faeni, and pooled sIgG levels, respectively. The 4-mold panel (positive if any sIgG exceeded cutoff) showed 57.1% sensitivity and 78.1% specificity for HP diagnosis among ILD subjects. The pooled sIgG test (positive likelihood ratio, 3.29; negative likelihood ratio, 0.51) shifted post-test probability of HP diagnosis from 44% (for a negative test) to 84% (for a positive test). CONCLUSION:Mold-specific IgGs, when used at our proposed cutoffs, significantly alter post-test diagnostic probabilities; thus, can be used as an adjunct in multi-component HP diagnosis.

Primary renal neuroendocrine tumors (PRNETs) are exceptionally rare neoplasms that account for less than 1% of genitourinary neuroendocrine neoplasms and pose considerable diagnostic difficulty because of their non-specific clinicoradiological presentations and diverse histomorphology, which frequently mimics conventional renal epithelial tumors. We describe two adult patients with well-differentiated PRNET managed by partial nephrectomy including a 41-year-old male with a complex bosniak category IV cystic renal lesion, and another 43-year-old female with a tumor arising from the isthmus of a horse-shoe kidney. Both tumors showed organoid, trabecular, nested, tubulocystic, and focal cribriform architecture with low mitotic activity. Case 1 additionally showed focal capsular and perineural invasion despite of low-grade morphology. Tumor cells were diffusely positive for synaptophysin, chromogranin, and CD99, and negative for PAX8, CK7, CK20, WT1, TTF1, and CDX2, with a Ki-67 index below 2% in both. Electron microscopy confirmed dense-core neurosecretory granules, and both patients remain disease-free on radioimaging based follow-up. These cases illustrate that PRNET should be considered whenever a renal mass, including a complex cystic lesion or arising in a congenital anomalous kidney, not confirming thetypical epithelial morphology, and a combined histomorphological, immunohistochemical, and ultrastructural approach with prolonged surveillance is essential for accurate diagnosis and management.