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Abdominal Radiology (New York) Jun 2024The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities;...
PURPOSE
The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities; one of the latter is the low-grade oncocytic tumor (LOT). This study reports the radiologic appearance and clinical behavior of LOT.
METHODS
In this IRB-approved, HIPPA-compliant retrospective study, our institution's pathology database was searched for low-grade oncocytic tumors or neoplasms. Patient age, gender, and comorbidities were obtained from a review of electronic medical records, and imaging characteristics of the tumors were assessed through an imaging platform.
RESULTS
The pathology database search yielded 14 tumors in 14 patients. Four patients were excluded, as radiologic images were not available in three, and one did not fulfill diagnostic criteria after pathology re-review. The resulting cohort consisted of 10 tumors (median diameter 2.3 cm, range 0.7-5.1) in 10 patients (median age 68 years, range 53-91, six women). All tumors presented as a solitary, well-circumscribed, mass with solid components. All enhanced as much or almost as much as adjacent renal parenchyma; all but one enhanced heterogeneously. None had lymphadenopathy, venous invasion, or metastatic disease at presentation or at clinical follow-up (median, 22.2 months, range 3.4-71.6). Among five tumors undergoing active surveillance, mean increase in size was 0.4 cm/year at imaging follow-up (median 16.7 months, range 8.9-25.4).
CONCLUSION
LOT, a recently described pathologic entity in the kidney, can be considered in the differential diagnosis of an avidly and typically heterogeneously enhancing solid renal mass in an adult patient.
Topics: Humans; Female; Male; Aged; Middle Aged; Kidney Neoplasms; Retrospective Studies; Aged, 80 and over; Adenoma, Oxyphilic; Neoplasm Grading; Contrast Media; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Diagnosis, Differential
PubMed: 38372764
DOI: 10.1007/s00261-023-04167-7 -
ACS Chemical Biology Feb 2024Altered metabolism is a hallmark of cancer; however, it has been difficult to specifically target metabolism in cancer for therapeutic benefit. Cancers with genetically...
Altered metabolism is a hallmark of cancer; however, it has been difficult to specifically target metabolism in cancer for therapeutic benefit. Cancers with genetically defined defects in metabolic enzymes constitute a subset of cancers where targeting metabolism is potentially accessible. Hürthle cell carcinoma of the thyroid (HTC) tumors frequently harbor deleterious mitochondrial DNA (mtDNA) mutations in subunits of complex I of the mitochondrial electron transport chain (ETC). Previous work has shown that HTC models with deleterious mtDNA mutations exhibit mitochondrial ETC defects that expose lactate dehydrogenase (LDH) as a therapeutic vulnerability. Here, we performed forward genetic screens to identify mechanisms of resistance to small-molecule LDH inhibitors. We identified two distinct mechanisms of resistance: upregulation of an LDH isoform and a compound-specific resistance mutation. Using these tools, we demonstrate that the anticancer activity of LDH inhibitors in cell line and xenograft models of complex I mutant HTC is through on-target LDH inhibition.
Topics: Humans; L-Lactate Dehydrogenase; Mutation; Mitochondria; Thyroid Neoplasms; DNA, Mitochondrial; Adenoma, Oxyphilic
PubMed: 38270591
DOI: 10.1021/acschembio.3c00663 -
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 -
Pathology, Research and Practice Feb 2024Low grade oncocytic tumor (LOT) is a recently recognized renal oncocytic neoplasm with unique morphologic and immunohistochemical pattern (CK7 +, CD117 -) that...
CONTEXT
Low grade oncocytic tumor (LOT) is a recently recognized renal oncocytic neoplasm with unique morphologic and immunohistochemical pattern (CK7 +, CD117 -) that differentiates them from oncocytoma and chromophobe renal cell carcinoma (ChrRCC).
OBJECTIVE
To further evaluate the histomorphological characteristics as well as the clinical outcome of low grade oncocytic tumors, retrospectively.
DESIGN
Thirteen cases of LOT were identified from 463 cases of renal oncocytic neoplasm in our pathology archive. All tumors were immunostained with CK7, CD117 and other relevant markers. The pathohistological features and follow up data of these cases were recorded.
RESULTS
Median age of patients was 76 years old (range from 36 to 86), with male to female ratio of 2:11. None of the patients had a syndromic association/hereditary condition. Eleven tumors were unifocal in each affected kidney, and two were multifocal with 2 and 3 separated tumors, respectively. On microscopic examination, tumors show variety of growth patterns, namely solid, compact nested, focal tubular/tubuloreticular and trabecular patterns. The stroma can be hypocellular and edematous where the tumor cells are loosely arranged exhibiting cords and scattered single cell arrangement. Immunohistochemically, all thirteen cases displayed strong and diffuse CK7 positivity in tumor cells. Eleven cases were CD117 negative and the other two showed focal and weak CD117 positivity (< 5% of tumor cells). Uniform tumor cell positivity was found for AE1/3, EMA, PAX8, and e-cadherin. Negative staining results include CAIX, AMACR, CD10 and vimentin. All cases in our cohort demonstrate indolent behavior and show no evidence of disease recurrence, progression, or metastases during the follow-up period up to 96 months.
CONCLUSION
LOT is an emerging new entity of renal oncocytic neoplasm and demonstrates indolent clinical behavior. Its unique morphologic features and immunohistochemical patterns (CK7 +, CD117 -) set them apart from oncocytoma and ChrRCC.
Topics: Humans; Male; Female; Adult; Middle Aged; Aged; Aged, 80 and over; Kidney Neoplasms; Adenoma, Oxyphilic; Retrospective Studies; Biomarkers, Tumor; Neoplasm Recurrence, Local; Carcinoma, Renal Cell; Kidney
PubMed: 38241777
DOI: 10.1016/j.prp.2024.155127 -
Cytopathology : Official Journal of the... May 2024Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify...
BACKGROUND
Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify cytomorphologic features suggestive of parathyroid origin and to assess the utility of cytopathology in conjunction with ancillary tests in the identification of parathyroid glands.
MATERIALS AND METHODS
Ultrasound (US) guided FNA of parathyroid gland and lesions in 81 patients were reviewed concerning clinical history and correlated to histopathologic findings in available cases. FNA smears were evaluated for cellularity, architectural patterns, cellular and nuclear features, and background of the smears. In 78 cases, FNA was supplemented by a measurement of parathormone (PTH) levels in the needle washout fluid (FNA-PTH assay) and/or GATA3/PTH/chromogranin-A immunostainings.
RESULTS
Sixty-four cases were diagnosed cytologically as parathyroid lesions in conjunction with FNA-PTH assay and/or immunocytochemical examinations. In an additional nine cases, a diagnosis of parathyroid lesions was rendered after repeated FNA with FNA-PTH assay. The histolopathologic diagnosis of surgically excised cases (n = 75) included parathyroid adenoma (60 cases), atypical parathyroid adenoma (4 cases), parathyroid hyperplasia (10 cases), and parathyroid carcinoma (1 case). Major cytological findings of parathyroid tissue included high cellularity, scattered naked nuclei, cribriform and three-dimensional clusters, stippled chromatin, and oxyphilic cytoplasm while papillary pattern or colloid-like material was identified in three cases respectively. No nuclear grooves or inclusions were seen in any case.
CONCLUSIONS
High cellularity scattered naked nuclei, cribriform and three-dimensional patterns, stippled chromatin and oxyphilic cytoplasm are cytomorphologic features that favour parathyroid origin. A combination of these features with FNA-PTH assay and/or GATA3, PTH, and chromogranin-A immunostainings on cytologic specimens aid in the identification of parathyroid glands and the distinguishing of parathyroid from thyroid lesions.
Topics: Humans; Parathyroid Glands; Parathyroid Neoplasms; Biopsy, Fine-Needle; Chromogranins; Parathyroid Hormone; Adenoma; Chromatin
PubMed: 38213192
DOI: 10.1111/cyt.13356 -
JAMA Otolaryngology-- Head & Neck... Mar 2024Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was... (Review)
Review
IMPORTANCE
Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance.
OBSERVATIONS
Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma-with which it was formerly classified-and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine.
CONCLUSIONS AND RELEVANCE
The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.
Topics: Humans; Iodine Radioisotopes; Thyroid Neoplasms; Adenoma, Oxyphilic; Adenocarcinoma, Follicular; Lymphatic Metastasis
PubMed: 38206595
DOI: 10.1001/jamaoto.2023.4323 -
Frontiers in Endocrinology 2023Current guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective...
BACKGROUND
Current guidelines lack a standardized management for patients with family history of thyroid carcinoma (fTC),particularly benign thyroid neoplasm (fBTN). Our objective was to investigate the influence of various family histories on the selection of surgical approaches and disease-free survival (DFS).
METHODS
A cohort study was conducted involving 2261 patients diagnosed with differentiated thyroid carcinoma including those with fTC (n=224), fBTN (n=122), and individuals without a family history of thyroid carcinoma (nfTC; n=1915). Clinicopathological characteristics were collected. DFS was estimated using Kaplan-Meier analysis and factors affecting DFS were identified using Cox proportional hazard model.
RESULTS
Compared to nfTC, small tumor size, clinically lymph node-positive, extrathyroidal extension, vascular invasion, Hashimoto's disease and nodular goiter were more common in fTC and fBTN groups. They had lower T stage and a lower rate of good response to TSH suppression therapy but received more radioiodine therapy. It is worth noting that fTC is associated with male, bilateral and multifocal tumors, as well as central lymph node metastasis and distant metastasis. Both fTC (aHR = 2.45, 95% CI=1.11-5.38; = 0.03) and fBTN (aHR = 3.43, 95% CI=1.27-9.29; = 0.02) were independent predictors of DFS in patients who underwent lobectomy, but not total thyroidectomy. For 1-4 cm thyroid carcinomas with clinically node-negative, fTC was identified as an independent predictor, whereas fBTN was not.
CONCLUSION
Our findings indicate that a family history, particularly of malignancy, is associated with a more aggressive disease. Family history does not affect the prognosis of patients who undergo total thyroidectomy, but it may increase the risk of postoperative malignant events in those who have a lobectomy. Additionally, it may be necessary to monitor individuals with a family history of benign thyroid neoplasms.
Topics: Humans; Male; Disease-Free Survival; Cohort Studies; Iodine Radioisotopes; Retrospective Studies; Thyroid Neoplasms; Adenoma, Oxyphilic
PubMed: 38093963
DOI: 10.3389/fendo.2023.1282088 -
Indian Journal of Pathology &... 2023Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases... (Review)
Review
Renal oncocytoma is a benign renal neoplasm which has mostly been reported in adults. Occurrence in children is infrequent. To date, there are only six pediatric cases of renal oncocytoma reported previously. Herein, we report a 13-year-old girl presented with hematuria for a week. Abdominal computed tomography showed a well-defined heterogeneous solid mass with a stellate central scar in the left kidney. The patient underwent a nephron sparing surgery. Histopathological and immunohistochemical findings confirmed the diagnosis of renal oncocytoma. Though uncommon, renal oncocytoma should be considered as the differential diagnosis of renal tumor in children. In addition, intranuclear inclusions were firstly described in this pediatric patient with unclear significance, which need a large cohort to summarize and analyze.
Topics: Adolescent; Female; Humans; Adenoma, Oxyphilic; Diagnosis, Differential; Kidney Neoplasms; Tomography, X-Ray Computed
PubMed: 38084552
DOI: 10.4103/ijpm.ijpm_264_22 -
The American Journal of Surgical... Feb 2024Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell...
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.
Topics: Humans; Birt-Hogg-Dube Syndrome; Cities; Neural Cell Adhesion Molecule L1; Kidney Neoplasms; Carcinoma, Renal Cell; Adenoma, Oxyphilic
PubMed: 37994665
DOI: 10.1097/PAS.0000000000002152 -
Academic Radiology Apr 2024To evaluate the potential of quantitative measurements on contrast-enhanced CT (CECT) in differentiating small (≤4 cm) clear cell renal cell carcinoma (ccRCC) from...
RATIONALE AND OBJECTIVES
To evaluate the potential of quantitative measurements on contrast-enhanced CT (CECT) in differentiating small (≤4 cm) clear cell renal cell carcinoma (ccRCC) from benign renal tumors, including fat-poor angiomyolipoma (fpAML) and renal oncocytoma (RO).
MATERIALS AND METHODS
244 patients with pathologically confirmed ccRCC (n = 184) and benign renal tumors (fpAML, n = 50; RO, n = 10) were randomly assigned into training cohort (n = 193) and test cohort 1 (n = 51), while external test cohort 2 (n = 50) was from another hospital. Quantitative parameters were obtained from CECT (unenhanced phase, UP; corticomedullary phase, CMP; nephrographic phase, NP; excretory phase, EP) by measuring attenuation of renal mass and cortex and subsequently calculated. Univariable and multivariable logistic regression analyses were performed to evaluate the association between these parameters and ccRCC. Finally, the constructed models were compared with radiologists' diagnoses.
RESULTS
In univariable analysis, UP-related parameters, particularly UP (cortex minus tumor attenuation on UP), demonstrated AUC of 0.766 in training cohort, 0.901 in test cohort 1, 0.805 in test cohort 2. The heterogeneity-related parameter SD (standard deviation) showed AUC of 0.781, 0.834, and 0.875 respectively. In multivariable analysis, model 1 incorporating UP, NP (cortex minus tumor attenuation on NP), CMP-UP (tumor attenuation on CMP minus UP), and SD yielded AUC of 0.866, 0.923, and 0.949 respectively. When compared with radiologists, multivariate models demonstrated higher accuracy (0.800-0.860) and sensitivity (0.794-0.971) than radiologists' assessments (accuracy: 0.700-0.720, sensitivity: 0.588-0.706).
CONCLUSION
Quantitative measurements on CECT, particularly UP- and heterogeneity-related parameters, have potential to discriminate ccRCC and benign renal tumors (fpAML, RO).
Topics: Humans; Adenoma, Oxyphilic; Carcinoma, Renal Cell; Contrast Media; Diagnosis, Differential; Kidney Neoplasms; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 37945492
DOI: 10.1016/j.acra.2023.10.014