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Pathobiology : Journal of... 2021Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney arising from a precursor oncocytosis not associated with the Birt-Hogg-Dubé (BHD) syndrome is an unusual and...
Morphological and Molecular Study of Hybrid Oncocytic/Chromophobe Tumor of the Kidney Associated with Sporadic Renal Oncocytosis and Chronic B-Cell Lymphocytic Leukemia: The Possible Contribution of Lymphoma to Renal Oncocytosis.
Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney arising from a precursor oncocytosis not associated with the Birt-Hogg-Dubé (BHD) syndrome is an unusual and highly interesting neoplasm. Immunohistochemical and molecular findings suggest that HOCT is an entity distinct from both oncocytoma and chromophobe carcinoma. Although uncertainty persists regarding the factors predisposing to the development of HOCT, experimental findings suggest that it may arise due to the effect of toxins or in association with chronic kidney failure. The potential role of prior renal lymphoma in the development of oncocytosis has not hitherto been examined. We present a morphological, immunohistochemical, and molecular analysis of an HOCT arising from renal oncocytosis in conjunction with CLL affecting the kidney. The findings suggest that this tumor belongs to a family of similar neoplasms including oncocytoma, the eosinophilic variant of chromophobe renal-cell carcinoma (CRCC), and low-grade oncocytic tumor, even though these neoplasms may arise from different precursor lesions. HOCT and oncocytosis revealed the same immunohistochemical profile consistent on positivity for epithelial membrane antigen (EMA), cytokeratin 7 (Ck7), E-cadherin, CAM 5.2 and negativity for Pax-8, vimentin, renal-cell carcinoma (RCC) antigen, CD117, racemase, progesterone receptor, and CD10. The Ki-67 proliferation index was <1%. Molecular analysis of the tumor revealed the AKT3 gene mutation variant, classified as probably pathogenic, together with FOS1 gene amplification and no copy number variations (CNVs). Finally, we present a case of HOCT arising from a nonhereditary renal oncocytosis in conjunction with B lymphoma that raises interesting questions regarding pathogenesis.
Topics: Adenoma, Oxyphilic; Aged; Biomarkers, Tumor; Carcinoma, Renal Cell; Humans; Kidney; Kidney Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Male; Tomography, X-Ray Computed
PubMed: 33882490
DOI: 10.1159/000515215 -
International Braz J Urol : Official... 2014We reported a case of new-onset, multi-focal hepatic adenoma in an 18 year-old man with no classic risk factors occurring forty months after a renal transplant from a...
MAIN FINDINGS
We reported a case of new-onset, multi-focal hepatic adenoma in an 18 year-old man with no classic risk factors occurring forty months after a renal transplant from a cadaver donor. Histopathology of the adenoma was examined and genotype and phenotype were also analyzed. Histopathologic examination of the adenoma showed no malignancy. Genotype and phenotype analysis revealed no HNF1α or β-catenin gene mutations and no inflammatory infiltration. The patient was well and disease-free postoperatively. CASE HYPOTHESIS: Hepatic adenoma occurs mostly in those taking oral contraceptives or androgenic-anabolic steroids or in those with hereditary diseases. Hepatic adenoma in a renal transplant recipient is rare and has only been reported in one case with glycogen storage disease type Ia. Immunosuppressive treatment might have contributed to the development of the neoplasm.
PROMISING FUTURE IMPLICATIONS
Although malignant change occurs most often in β-catenin gene mutation hepatic adenoma, surgical resection of the adenoma in a patient under immunosuppressive therapy should be considered in order to avoid the possibility of malignant transformation or hemorrhagic rupture.
Topics: Adenoma; Adolescent; Biopsy; Cadaver; Cytokine Receptor gp130; Humans; Immunohistochemistry; Immunosuppressive Agents; Kidney Transplantation; Liver Neoplasms; Male; Tissue Donors; beta Catenin
PubMed: 24642158
DOI: 10.1590/S1677-5538.IBJU.2014.01.17 -
Archives of Pathology & Laboratory... Jun 2006Nephrogenic adenoma is a rare benign lesion of the urinary tract. Owing to its strong association with a history of urinary tract irritation, nephrogenic adenoma was...
CONTEXT
Nephrogenic adenoma is a rare benign lesion of the urinary tract. Owing to its strong association with a history of urinary tract irritation, nephrogenic adenoma was initially thought to originate from urothelial metaplasia; however, no solid proof of this association has been found. More recent investigation has pointed to a renal tubular cause. In addition to its uncertain origin, there can be diagnostic difficulty in distinguishing nephrogenic adenoma from prostatic carcinoma, particularly when dealing with lesions from the prostatic urethra.
OBJECTIVE
To elucidate a possible histogenic relationship between nephrogenic adenoma and renal tubules, and also to evaluate the role of immunohistochemistry in the diagnostic distinction between nephrogenic adenoma and prostate carcinoma.
DESIGN
Immunohistochemical studies were performed for P504S, prostate-specific antigen, CD10, p63, and epithelial membrane antigen on 9 cases of nephrogenic adenoma, 10 cases of normal renal parenchyma, and 10 cases of prostatic tissue, both benign and malignant.
RESULTS
Nephrogenic adenoma shares the same immunohistochemical profile as distal renal tubules: both are positive for P504S and epithelial membrane antigen and negative for p63, CD10, and prostate-specific antigen. Prostatic adenocarcinoma tissue was positive for P504S and prostate-specific antigen, and normal prostatic gland tissue was positive for prostate-specific antigen and negative for P504S; p63-stained basal cells in normal prostatic gland tissue but did not react with prostatic adenocarcinoma tissue. The CD10 inconsistently stained normal and neoplastic prostatic gland tissue. Epithelial membrane antigen stain was negative in prostatic carcinoma, with rare occasional reactivity in normal prostatic glands.
CONCLUSION
These findings provide supporting evidence that nephrogenic adenoma is derived from distal renal tubules. Our results also demonstrated that the combination of P504S and prostate-specific antigen with epithelial membrane antigen is a valuable tool in distinguishing prostatic carcinoma from nephrogenic adenoma.
Topics: Adenocarcinoma; Adenoma; Biomarkers, Tumor; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Mucin-1; Prostatic Neoplasms; Racemases and Epimerases; Urologic Neoplasms; Urothelium
PubMed: 16740031
DOI: 10.5858/2006-130-805-NAIEFI -
Pathology Jan 2016Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from...
Renal oncocytosis is a rare pathological condition characterised by the presence of multiple oncocytic tumours with a spectrum of histological features ranging from renal oncocytoma, hybrid oncocytic tumour and rarely chromophobe renal cell carcinoma, sometimes overlapping. Here we retrospectively analysed histological, immunohistochemical (IHC), and cytogenetic features of 42 lesions in 11 patients with renal oncocytosis, not associated with Birt-Hogg-Dubé syndrome. The histology of all the lesions was blindly reviewed by three dedicated genitourinary pathologists. IHC for cytokeratin 7 (CK7) and fluorescence in situ hybridisation (FISH) for copy number variation of chromosomes 1, 6, 7 and 17 were performed in all 42 nodules. Among the 42 lesions 36 (85.7%) were histologically renal oncocytomas, two (4.76%) 'hybrid oncocytic tumours' (HOT), one (2.4%) clear cell renal cell carcinoma (ccRCC), one (2.4%) papillary renal cell carcinoma (pRCC), one typical angiomyolipoma (2.4%), and one mixed epithelial/stromal tumour of the kidney (2.4%). FISH analysis confirmed the histological diagnosis of all the lesions. We show that most patients with renal oncocytosis harbour benign or low malignant potential tumours that can be treated conservatively.
Topics: Adenoma, Oxyphilic; Adult; Aged; Aged, 80 and over; Angiomyolipoma; Carcinoma, Renal Cell; DNA Copy Number Variations; Female; Humans; In Situ Hybridization, Fluorescence; Kidney; Kidney Neoplasms; Male; Middle Aged; Retrospective Studies
PubMed: 27020208
DOI: 10.1016/j.pathol.2015.11.009 -
Archives of Pathology & Laboratory... Jun 2002
Review
Topics: Adenoma, Oxyphilic; Humans; Kidney; Kidney Failure, Chronic; Kidney Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Tomography, X-Ray Computed
PubMed: 12087966
DOI: 10.5858/2002-126-0648-BROWRF -
Nefrologia 2019Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterised by hypercalcaemia and parathormone increase. Decreased glomerular filtration rate... (Observational Study)
Observational Study
INTRODUCTION
Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterised by hypercalcaemia and parathormone increase. Decreased glomerular filtration rate (<60ml/min) continues to be a parathyroidectomy (PTX) criterion in asymptomatic PHPT. The influence of PTX on renal function evolution is the subject of debate.
OBJECTIVE
To analyse the clinical, laboratory and histological characteristics of patients undergoing PHPT, as well as renal function evolution after PTX.
MATERIAL AND METHODS
Retrospective study of 297 patients diagnosed with PHPT and referred to surgery in a single centre between 1998 and 2016. Laboratory parameters were determined at baseline, one week and one year after PTX.
RESULTS
The Incidence of PTX was 38 cases/million/year. Mean age was 60±14 years and 80.5% of the patients were female. Approximately 65.3% were asymptomatic. Nephrolithiasis was the most common clinical finding (33%), followed by bone involvement (29.5%). PTX indications were: clinical symptoms (34.7%), hypercalcaemia>11.2mg/dl (27%), nephrolithiasis (13%), low bone mass (12%), age<50 years (11%) and decreased glomerular filtration rate<60ml/min (2.3%). For diagnostic localisation, spect-MIBI had a sensitivity of 92% and cervical ultrasound of 70%. A total of 94.3% of PHPT cases were due to a parathyroid adenoma. After PTX, normalisation of PHPT-related parameters was observed. We found a significant increase in serum creatinine levels (0.81 vs 0.85mg/dl, P<.001) from the first week post-PTX until the end of the first year. The renal function was only found to be significant in patients with glomerular filtration rate>60ml/min (baseline serum creatinine levels 0.77mg/dl vs serum creatinine levels after one year 0.81mg/dl, P<.001).
CONCLUSIONS
PHPT was asymptomatic in most patients who underwent surgery. Hypercalcaemia and nephrolithiasis were the most common indications of parathyroidectomy in asymptomatic patients. MIBI scan was the most useful localisation method. Surgical treatment of PHPT is followed by renal function impairment, which persists after the first week post-PTX.
Topics: Adenoma; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Kidney; Male; Middle Aged; Nephrolithiasis; Osteoporosis; Parathyroid Neoplasms; Parathyroidectomy; Recovery of Function; Retrospective Studies
PubMed: 30459009
DOI: 10.1016/j.nefro.2018.08.007 -
BMC Medical Genetics Oct 2020Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell...
BACKGROUND
Metanephric adenoma (MA) is a rare benign renal neoplasm. On occasion, MA can be difficult to differentiate from renal malignancies such as papillary renal cell carcinoma in adults and Wilms̕ tumor in children. Despite recent advancements in tumor genomics, there is limited data available regarding the genetic alterations characteristic of MA. The purpose of this study is to determine the frequency of metanephric adenoma cases exhibiting cytogenetic aberration t (9;15)(p24;q24), and to investigate the association between t (9,15) and BRAF mutation in metanephric adenoma.
METHODS
This study was conducted on 28 archival formalin fixed paraffin-embedded (FFPE) specimens from patients with pathologically confirmed MA. Tissue blocks were selected for BRAF sequencing and fluorescent in situ hybridization (FISH) analysis for chromosomal rearrangement between KANK1 on chromosome 9 (9p24.3) and NTRK3 on chromosome 15 (15q25.3), which was previously characterized and described in two MA cases.
RESULTS
BRAF mutation was identified in 62% of our cases, 9 (38%) cases were BRAF, and 4 cases were uninformative. Of the 20 tumors with FISH results, two (10%) were positive for KANK1-NTRK3 fusion. Both cases were BRAF suggesting mutual exclusivity of BRAF and KANK1-NTRK3 fusion, the first such observation in the literature.
CONCLUSIONS
Our data shows that BRAF mutation in MA may not be as frequent as suggested in the literature and KANK-NTRK3 fusions may account for a subset of BRAF cases in younger patients. FISH analysis for KANK1-NTRK3 fusion or conventional cytogenetic analysis may be warranted to establish the diagnosis of MA in morphologically and immunohistochemically ambiguous MA cases lacking BRAF mutations.
Topics: Adaptor Proteins, Signal Transducing; Adenoma; Adolescent; Adult; Aged; Child; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 9; Cytoskeletal Proteins; Female; Humans; In Situ Hybridization, Fluorescence; Kidney Neoplasms; Male; Middle Aged; Mutation; Oncogene Proteins, Fusion; Proto-Oncogene Proteins B-raf; Receptor, trkC; Translocation, Genetic; Young Adult
PubMed: 33046021
DOI: 10.1186/s12881-020-01143-6 -
Journal of Cancer Research and... 2015Villous adenoma is a rare primary tumor of the urinary system, especially the bladder and kidneys. This study presents two cases of right pelvis villous adenoma,... (Review)
Review
Villous adenoma is a rare primary tumor of the urinary system, especially the bladder and kidneys. This study presents two cases of right pelvis villous adenoma, including that of a 61-year-old patient who had experienced hematuria for more than 1 year and was diagnosed with bladder and ureteral stones via B-ultrasound examination, and the other one involving a 65-year-old patient who was hospitalized for 6 days due to a right upper quadrant mass and diagnosed with right renal pelvis stones and hydrops via B-ultrasound examination. Both patients underwent nephrectomy, and their histological analysis demonstrated papillary projections covered by columnar cells and goblet cells. The first patient had a large amount of renal pelvis mucus accumulation with obvious microscopic intestinal metaplasia and mild-moderate nuclear atypia. Immunohistochemical studies revealed positive carcinoembryonic antigen and the caudal type homeobox 2 staining with varying degrees of cytokeratin (CK)-7 and CK20 expression in both patients. Recurrences or metastasis was not observed during the follow-up period of 3-4 years.
Topics: Adenoma, Villous; Aged; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged
PubMed: 26458689
DOI: 10.4103/0973-1482.144653 -
Cells Jan 2022Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The...
Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.
Topics: Adenoma, Oxyphilic; Algorithms; Carbohydrate Metabolism; Carcinoma, Renal Cell; Databases, Genetic; Diagnosis, Differential; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Humans; Machine Learning; ROC Curve; Reproducibility of Results; Warburg Effect, Oncologic
PubMed: 35053403
DOI: 10.3390/cells11020287 -
Turk Patoloji Dergisi 2024The classification of renal tumors is expanding with the addition of new molecular entities in the 5th World Health Organization classification. Apart from this, the...
OBJECTIVE
The classification of renal tumors is expanding with the addition of new molecular entities in the 5th World Health Organization classification. Apart from this, the major updates in the definition of papillary renal cell carcinoma are that these tumors are no longer subtyped into type 1 and type 2. In oncocytic tumors, the new molecularly defined renal tumors, emerging and novel entities need to be considered in the diagnosis of oncocytic and chromophobe renal tumors.
MATERIAL AND METHODS
This is a retrospective study to review and reclassify papillary, oncocytic, and chromophobe renal tumors based on the new WHO classification and correlate with clinical data, gross, microscopic features, and immunohistochemistry markers.
RESULTS
A total of thirteen cases were reviewed and the tumor grade was changed for three out of four cases of papillary renal cell carcinoma and a single case was recategorized and graded. In nine cases of oncocytic and chromophobe renal tumors, the diagnoses were modified in 3 cases.
CONCLUSION
Newly defined molecular renal tumors require advanced immunohistochemistry markers and molecular tests. This poses diagnostic challenges to pathologists practicing in low resource settings where molecular tests are not available.
Topics: Humans; Kidney Neoplasms; Retrospective Studies; Male; Female; Carcinoma, Renal Cell; Middle Aged; Aged; World Health Organization; Biomarkers, Tumor; Adult; Immunohistochemistry; Adenoma, Oxyphilic; Neoplasm Grading
PubMed: 38265103
DOI: 10.5146/tjpath.2024.13052