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Cowper glands recognition remains one of the key histoanatomic benign mimics of prostatic adenocarcinoma. In most instances, these can be identified based on the dimorphic population of lobulated acini and duct(s). However, in the prostate biopsy setting with incomplete/distorted cores, this may not be immediately apparent and may warrant use of immunohistochemistry to argue against prostatic adenocarcinoma. Although immunohistochemical pitfalls in Cowper glands have been described, to our knowledge a comprehensive evaluation of both traditional and purportedly prostate-specific novel markers in Cowper glands has not been previously performed. Herein, we studied the clinicopathological and immunohistochemical features of 21 male patients (age range 39-81 years; mean = 63 years), including 15 prostate biopsies (7 of which also had prostate cancer in the same specimen set and 2 of which had both prostate cancer and Cowper glands in the same biopsy core). Immunohistochemistry showed the following results in Cowper glands: 100% positive for NKX3.1, 100% positive (basal cells) for both high molecular weight keratin and p63, 57% positive for PSAP, 25% positive for PSMA, 5% positive for AMACR, and 0% positive for PSA. In conclusion, for specimens lacking appreciable dimorphic morphology, caution should be rendered when using prostate-specific markers (PSA, PSAP, PSMA, and NKX3.1) as these can show considerable staining in Cowper glands and be a pitfall. Instead, findings from this cohort indicate relying on basal markers (high molecular weight keratin/p63; either individually or in a "cocktail" approach) and PSA are most useful in distinguishing Cowper glands (retained basal cell markers staining) from prostatic adenocarcinoma.
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AIMS: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. METHODS AND RESULTS: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. CONCLUSION: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.
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BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.
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Carcinoma de Células Renais , Neoplasias Renais , Nefrectomia , Nivolumabe , Humanos , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Masculino , Feminino , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Pessoa de Meia-Idade , Idoso , Canadá , Quimioterapia Adjuvante , Estadiamento de Neoplasias , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagemRESUMO
PURPOSE: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. METHODS: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. RESULTS: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. CONCLUSIONS: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial.
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Urothelial carcinoma and prostatic adenocarcinoma can have overlapping histologic features and in some instances pose challenges to pathologists. GATA binding protein 3 (GATA3) immunohistochemistry (IHC) is a well-established tool to aid in this specific diagnostic dilemma as it has been shown to be a sensitive marker for urothelial carcinoma and a putatively specific marker in excluding prostatic adenocarcinoma. However, in encountering an index tumor of prostatic adenosquamous carcinoma positive for GATA3, herein we sought to investigate this potential diagnostic pitfall in a larger series of tumors. In this study, we retrospectively reviewed prostatic adenosquamous carcinomas diagnosed in 17 patients across the authors' institutions and personal consult collections in the past 10 years. GATA3 IHC was either reviewed or performed on tumors not previously tested. We also recorded other immunostains that were performed at initial diagnosis. Positivity for GATA3 was found in 9 of 17 (53%) tumors, all within squamous regions (2 tumors also showed concomitant moderate GATA3 positivity within glandular elements). The GATA3 positive tumors were all positive for p63 in the 7 tumors where p63 was also performed. Of all tumors tested, NKX3.1 was positive in 100% (13/13) of the glandular elements (3 tumors also showed NKX3.1 concomitant positivity within squamous regions). In summary, when encountering a carcinoma with mixed glandular/squamous features in which prostatic origin is being considered, awareness of GATA3 immunoreactivity in a subset of prostatic adenosquamous carcinoma is critical to avoid diagnostic pitfalls.
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In addition to "classic" and eosinophilic subtype, chromophobe renal cell carcinoma (RCC) is well-known to demonstrate various morphological patterns including adenomatoid, microcystic, pigmented, multicystic, papillary, neuroendocrine-like, and small cell-like, all of which are important to appreciate for accurate diagnosis. Herein, we expand on a unique chromophobe RCC morphology not previously described consisting of tumor cells with extensive stromal retraction, mimicking upper urothelial tract micropapillary carcinoma (MPC). Twelve MPC-like chromophobe RCC nephrectomies were reviewed with clinicopathological features recorded; molecular testing was performed on 7 of 12 tumors. Patients were mostly men (n=10) with a mean age of 65 years. Mean tumor size was 6.4 cm with pathological stage distribution as follows: 4 (33%) T1a, 2 (17%) T1b, 1 (8%) T2b, and 3 (25%) T3a. The extent of MPC-like chromophobe RCC foci ranged from 10% to 40% (mean=26%; there was no correlation between the extent of MPC-like chromophobe RCC foci and tumor stage). Other chromophobe RCC morphological patterns were not identified. When performed, all (100%) tumors depicted prototypic chromophobe RCC staining pattern of KIT positivity/KRT7 positivity. Molecular showed 6 of 7 (86%) with multiple chromosomal losses. Clinically significant mutations were identified in NF1, TP53, FLCN (likely somatic), CHEK2, and ZFHX3 genes. Follow up available in 9 patients showed no evidence of disease (mean=23 months). Although the etiology behind the extensive stromal retraction in our tumors is unknown, this may likely be artifactual in nature. Nonetheless, it is important to include MPC-like chromophobe RCC in the spectrum of "variant" morphologies to avoid diagnostic pitfalls from micropapillary carcinoma.
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PURPOSE: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. METHODS: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. RESULTS: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. CONCLUSIONS: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.
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Background and Objective: Inflammatory myofibroblastic tumor (IMT) is a rare entity that is described in several organ systems. This comprehensive review aims to identify IMTs occurring at various genitourinary (GU) organ sites and describe patterns of clinical management in adult and pediatric patients. Methods: A comprehensive search of PubMed and Web of Science was conducted according to the Preferred Reporting Items for Systematic Review and meta-analyses statement. Two reviewers performed independent initial screening of abstracts. Eligible articles underwent full review and data extraction. The clinical features, diagnostic tests, treatment, and outcomes at each GU organ site were analyzed individually and summarized into a comprehensive review. Key Content and Findings: Of the 270 articles identified, 112 met inclusion criteria. Articles primarily consisted of case reports or small series describing a total of 167 cases, of which 30 (18%) occurred in children. Most patients (96%) were symptomatic at presentation. The most frequently involved sites included bladder (106 cases) and kidney (n=33) followed by epididymis (n=6), urachus (n=6), ureter (n=5), prostate (n=4), testis (n=4), and spermatic cord (n=3). Complete surgical excision of the mass including partial or total removal of involved organs provided excellent outcomes. Incomplete excision was associated with early local recurrence and progression. Late recurrence or metastatic transformation was rarely noted (<2%). Conclusions: IMTs exhibit locally invasive, symptomatic and progressive phenotypes that affect all urologic organs in adults and children. Clinical features and imaging results are similar to those noted with urologic cancers. These tumors require complete surgical excision since incomplete resection increases the risk of symptomatic recurrence.
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The recent influx of novel renal neoplasms, particularly molecularly-defined renal carcinomas, has introduced new challenges in the daily practice of most pathology laboratories. These tumors are uncommon, they do not always have well-established morphologic features, and the expression profile of most common biomarkers is not well understood. Moreover, the diagnosis of molecularly-defined renal carcinomas requires the documentation of the disease-defining molecular alteration, with molecular studies or surrogate immunohistochemical markers. Unfortunately, most pathology laboratories lack molecular laboratories, or it is not cost-effective to maintain assays of the specific biomarkers in these unusual tumors. Pathologists should have updated knowledge about the recent changes in renal neoplasms and be aware of these limitations.
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Biphasic papillary renal cell carcinoma (synonymous with biphasic squamoid alveolar renal cell carcinoma) is considered within the spectrum of papillary renal cell carcinoma (PRCC). With < 70 reported cases of biphasic PRCC, there is limited data on the pathologic spectrum and clinical course. Seventeen biphasic PRCC cases and 10 papillary adenomas with similar biphasic morphology were assessed. The mean age of the biphasic PRCC patients was 62 years (male to female ratio of 1.8:1), from 10 partial nephrectomies, 6 radical nephrectomies, and 1 biopsy. The mean tumor size was 3.6 cm (range 1.6-8 cm), with 24% showing multifocality. Fifteen out of 17 cases were limited to the kidney (one of which was staged as pT2a but had lung metastases at diagnosis) and 2/17 cases were staged as T3a. All tumors showed typical biphasic morphology with an extent of squamoid foci widely variable from 10 to 95%. Emperipolesis was identified in 88% of cases. All biphasic PRCC tested exhibited positivity for PAX8 (16/16), keratin 7 (17/17), EMA (15/15), AMACR (17/17), and vimentin (12/12) in both large and small cells; cyclin D1 was only expressed in the large cells (16/16). The 10 papillary adenomas showed a similar immunoprofile to biphasic PRCC. NGS testing performed on 13 biphasic PRCC revealed 4 (31%) harboring MET SNVs. In 1/5 (20%) papillary adenomas, a pathogenic MET SNV was identified. Biphasic PRCC is rare with a generally similar immunoprofile to "type 1" PRCC but with notable strong positivity for cyclin D1 in the large cell component. Although most of the biphasic PRCC cases were of small size, low stage, and with an indolent behavior, one patient had metastatic disease and one patient died of the disease.
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Adenoma , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Ciclina D1 , Biomarcadores Tumorais , Imuno-HistoquímicaRESUMO
Atrophic kidney-like lesion (AKLL) is a rare kidney lesion, which was recently suggested by the Genitourinary Pathology Society as a provisional entity. As of now, 16 examples of AKLL have been described in the literature. Here we report a new tumor which shows similar clinicopathologic characteristics with those previously reported in AKLL. Immunohistochemical (IHC) studies in the current lesion identified a biphasic staining pattern consisting of a mixture of WT1+/KRT7-/PAX8- large dilated cysts and WT-/KRT7+/PAX8+ small atrophic cysts. Histomorphologic features of AKLL overlap with several neoplastic and non-neoplastic entities which can lead to mischaracterization. Awareness of the differentiating features is likely important when evaluating these lesions.
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The differential diagnosis for oncocytic renal tumors spans the spectrum from benign entities to more aggressive renal cell carcinomas (RCC). Recent work has characterized a provisional renal oncocytic neoplasm, namely the low-grade oncocytic tumor (LOT), which demonstrates overlapping morphologic features with oncocytoma and chromophobe RCC, but also has a unique immunoprofile (ie, diffusely positive for KRT7, negative for KIT) and a high rate (80% to 100%) of mTOR pathway gene alterations. Given the diagnostic overlap among oncocytic tumors, we looked for concordance between mTOR pathway mutations and LOT. Thirty low-grade renal oncocytic neoplasms underwent histologic review and immunohistochemistry for KRT7 and KIT. Tumors were classified as "determinate" (eg, LOT) for tumors with solid, nested or vaguely tubular growth and diffuse KRT7 staining and negative KIT, or "indeterminate" if the morphology and/or immunostains did not fully support a definitive LOT diagnosis. Next-generation sequencing was performed without any knowledge of the diagnoses, and identified mTOR pathway mutations in 80% (12/15) of the determinate tumors, compared with 7% (1/15) in the indeterminate group. One determinate tumor was reclassified as papillary RCC (MTOR mutation negative) and 6 indeterminate tumors were confirmed to be oncocytoma (N = 4), clear cell RCC or papillary RCC with reverse polarity, respectively. Overall, integration of morphology, immunohistochemistry, and molecular data enabled a final definitive diagnosis for 70% of tumors (21 of the total 30), with a high concordance (93%) for LOT specifically in the determinate group; the remaining 9 tumors (30%) were classified as renal oncocytic neoplasm, not otherwise specified.
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Adenoma Oxífilo , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Adenoma Oxífilo/diagnóstico , Adenoma Oxífilo/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Mutação , Diagnóstico Diferencial , Serina-Treonina Quinases TOR/genética , Biomarcadores Tumorais/genéticaRESUMO
Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (n = 6). Patients were predominately female (n = 7) with a median age of 48 years (35-62 years). The most common primary location of the AdCC was head and neck (n = 6, among them parotid gland = 4), followed by lung (n = 2), breast (n = 1), and vulva (n = 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1-336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.
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Carcinoma Adenoide Cístico , Neoplasias Renais , Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma Adenoide Cístico/patologia , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/secundário , Recidiva Local de Neoplasia/patologia , Glândula Parótida/patologiaRESUMO
Accurate diagnosis of neuroblastoma may be challenging, especially with limited or inadequate specimen and at the metastatic sites due to overlapping imaging, histopathologic, and immunohistochemical (immunohistochemistry [IHC]; infidelity among various lineage-associated transcription factors eg FLI1, transducin-like enhancer 1, etc) features. GATA3 and ISL1 have recently been described as markers of neuroblastic differentiation. This study aims at determining the diagnostic utility of GATA3 and ISL1 in differentiating neuroblastoma from other pediatric malignant small round blue cell tumors.We evaluated GATA3 and ISL1 expression in 74 pediatric small round blue cell tumors that included 23 NMYC-amplified neuroblastomas, 11 EWSR1-rearranged round cell sarcomas, 7 SYT::SSX1-rearranged synovial sarcomas, 5 embryonal rhabdomyosarcomas, 10 Wilms tumors (nephroblastomas), 7 lymphoblastic lymphoma, 7 medulloblastoma, and 4 desmoplastic small round cell tumor.All 23 neuroblastomas (moderate to strong staining in >50% of the tumor cells), 5â T-lymphoblastic lymphomas (moderate to strong staining in 40%-90% of the tumor cells), and 2 desmoplastic small round cell tumors (weak to moderate staining in 20%-30% of the tumor cells) expressed GATA3, while other tumors were negative. ISL1 immunoreactivity was observed in 22 (96%) neuroblastomas (strong staining in in >50% of the tumor cells, n = 17; moderate to strong staining in 26%-50% of the tumor cells, n = 5), 3 embryonal rhabdomyosarcoma (moderate to strong staining in 30%-85% of the tumor cells), 1 synovial sarcoma (weak staining in 20% of the tumor cells), and 7 medulloblastoma (strong staining in 60%-90% of the tumor cells). Other tumors were negative. Overall, GATA3 showed 86% specificity, 100% sensitivity, and 90% accuracy for neuroblastoma, with a positive predictive value (PPV) and negative predictive value (NPV) of 77% and 100%, respectively. ISLI showed 72% specificity, 96% sensitivity, and 81% accuracy for neuroblastoma, with a PPV and NPV of 67% and 97%, respectively. After the exclusion of T-lymphoblastic lymphoma and desmoplastic small round cell tumors, GATA3 had 100% specificity, sensitivity, accuracy, and PPV and NPV for neuroblastoma. Similarly, in pediatric small round blue cell tumors, ISL1 had 100% specificity, sensitivity, accuracy, PPV, and NPV for neuroblastoma, after embryonal rhabdomyosarcoma, synovial sarcoma, and medulloblastoma were excluded. CONCLUSIONS: GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up.
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Neoplasias Cerebelares , Neoplasias Renais , Meduloblastoma , Neuroblastoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Rabdomiossarcoma Embrionário , Sarcoma Sinovial , Tumor de Wilms , Humanos , Criança , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/genética , Neuroblastoma/diagnóstico , Tumor de Wilms/diagnóstico , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biomarcadores Tumorais , Diagnóstico Diferencial , Fator de Transcrição GATA3RESUMO
Fumarate hydratase deficient renal cell carcinoma (FHRCC) can exhibit a heterogenous immunoprofile. In the present case, a solitary 10.5â cm mixed cystic and solid left kidney tumor showed various growth patterns, involving renal sinus adipose tissue and the renal pelvis. Tumor cells showed prominent nucleoli and perinucleolar halos. Aberrant diffuse (>90%), strong, and membranous carbonic anhydrase 9 and variable GATA3 expression were present. Diagnostic loss of fumarate hydratase expression and 2-succinyl cysteine overexpression (cytoplasmic and nuclear) were identified. Carbonic anhydrase 9 and GATA3 expression in FHRCC is rarely reported in the literature, and may cause misdiagnosis of clear cell RCC and/or urothelial carcinoma.
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Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Fumarato Hidratase/genética , Anidrase Carbônica IX , Fator de Transcrição GATA3RESUMO
In some instances, the central scar of renal oncocytoma can demonstrate entrapped cells with unusual morphology and aberrant immunoprofile creating potential diagnostic confusion. Herein, 100 renal oncocytomas containing scars with embedded epithelial cells were identified from 6 institutions, including nephrectomies (64% partial, 36% radical) of similar laterality (left = 51%) and sex distribution (male = 56%), with patient ages ranging from 38 to 86 years (mean = 64.3years) and tumor sizes ranging from 2 to 16â cm (mean = 5.3â cm). Immunohistochemistry was performed on all tumors for KRT7, KIT, vimentin, and CA9 with staining intensity and extensity separately analyzed. Of 4 architectural patterns of cells within the scar, 60% showed tubular pattern. Of 4 cytologies within the scar, flat/elongated (49%) and cuboidal cells (40%) predominated. Within the scar, 62% showed eosinophilic cytoplasm, with 38% showing both cleared and eosinophilic cytoplasm; notably, 79% showed higher grade nuclei than typical oncocytes. A subset of scar cells showed mucinous-like basophilic secretions (19%). Compared to background renal oncocytoma, tumor cells within the scar were more often positive for vimentin, KRT7, and CA9 and more frequently negativity for KIT. Specifically, of the notable "aberrant" immunoprofiles, 79% showed KRT7 positivity/KIT negativity/vimentin positive, 84% showed vimentin positivity/CA9 positivity, and 78% showed KIT negativity/vimentin positivity/CA9 positivity. While encountering scars within renal oncocytomas is not uncommon, what is not well appreciated is the unique morphology and immunohistochemistry of tumor cells within the scar. Comparing tumor morphology and immunoprofile of the scar to the background oncocytoma is helpful to avoid interpretative confusion.
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Adenoma Oxífilo , Carcinoma de Células Renais , Neoplasias Renais , Masculino , Humanos , Adenoma Oxífilo/diagnóstico , Adenoma Oxífilo/cirurgia , Adenoma Oxífilo/patologia , Carcinoma de Células Renais/patologia , Vimentina , Cicatriz/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Diagnóstico DiferencialRESUMO
BACKGROUND: Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis. CASE PRESENTATION: Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors. CONCLUSIONS: We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs.
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Melanoma , Neoplasias Penianas , Neoplasias Cutâneas , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/patologia , Antígeno B7-H1 , Antígenos de NeoplasiasRESUMO
Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm known to occur at various soft tissue and visceral locations. Kidney is a rarely reported site for these tumors. Most of the SFTs described in the kidney exhibit a classical CD34-positive patternless spindle cell histology. Focal round cell morphology is seldom reported. Herein, we describe a 48-year-old male patient with renal SFT. This tumor had pure round cell morphology with a CD34-/STAT6+ immunophenotype. Fluorescent in situ hybridization and a multiplexed sequencing assay performed on an Illumina® HiSeq 4000 platform revealed NAB2 and STAT6 gene rearrangement. Renal tumors with round cell morphology are diagnostically challenging and SFT is not often considered in the differential diagnosis of a round cell tumor of the kidney. Moreover, a CD34-negative profile can be rather confounding while diagnosing such lesions. In such scenarios, a strong nuclear STAT6 immunostaining is extremely helpful in clinching the diagnosis. SFT should always be considered in the differential diagnosis of round cell tumors of the kidney due to significant diagnostic and therapeutic implications.