CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
- MeSH
- buněčné jádro patologie MeSH
- folikulární adenokarcinom * patologie epidemiologie diagnóza MeSH
- lékařská praxe - způsoby provádění statistika a číselné údaje MeSH
- lidé MeSH
- nádory štítné žlázy * epidemiologie patologie diagnóza MeSH
- papilární karcinom štítné žlázy epidemiologie patologie diagnóza MeSH
- papilární karcinom patologie epidemiologie diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Asie MeSH
- Evropa MeSH
- Oceánie MeSH
- Severní Amerika MeSH
Papillary renal neoplasm with reversed polarity (PRNRP) is a recently described rare renal neoplasm. Traditionally, it was considered a variant of papillary renal cell carcinoma (PRCC). However, several studies reported significant differences between PRNRP and PRCC in terms of clinical, morphological, immunohistochemical and molecular features. Nonetheless, PRNRP remains a poorly understood entity. We used microarray analysis to elucidate the non-coding RNA (ncRNA) and gene expression profiles of 10 PRNRP cases and compared them with other renal neoplasms. Unsupervised cluster analysis showed that PRNRP had distinct expression profiles from either clear cell renal cell carcinoma (ccRCC) or PRCC cases at the level of ncRNA but were less distinct at the level of gene expression. An integrated omic approach determined miRNA:gene interactions that distinguished PRNRP from PRCC and we validated 10 differentially expressed miRNAs and six genes by quantitative RT-PCR. We found that levels of the miRNAs, miR-148a, miR-375 and miR-429, were up-regulated in PRNRP cases compared to ccRCC and PRCC. miRNA target genes, including KRAS and VEGFA oncogenes, and CXCL8, which regulates VEGFA, were also differentially expressed between renal neoplasms. Gene set enrichment analysis (GSEA) determined different activation of metabolic pathways between PRNRP and PRCC cases. Overall, this study is by far the largest molecular study of PRNRP cases and the first to investigate either ncRNA expression or their gene expression by microarray assays.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk * genetika patologie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory ledvin * genetika patologie metabolismus MeSH
- nekódující RNA * genetika MeSH
- papilární karcinom patologie genetika metabolismus MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Warthin-like papilokarcinom štítné žlázy je vzácnou variantou papilokarcinomu s velice dobrou prognózou. Často bývá asociován s lymfocytární thyreoiditis. Pro svůj typický histologický obraz připomínající Warthinův tumor slinných žláz nebývá histologická diagnóza obtížná, obvykle nevyžaduje doprovodné imunohistochemické vyšetření a je založena na přítomnosti jaderných znaků typických pro papilární karcinom a přítomnosti onkocytů na pozadí tvořeném bohatým lymfocytárním infiltrátem. Úskalí přináší předoperační cytologické vyšetření, kdy obdobný obraz může mít řada dalších lézí. Postihuje častěji ženy. Objevuje se o dekádu dříve než klasická varianta. Klinicky se projevuje obdobně jako konvenční papilární karcinom. V naší kazuistice bychom rádi prezentovali případ 56leté ženy s netoxickou mnohauzlovou strumou, u které histologické vyšetření odhalilo přítomnost této vzácné varianty papilárního karcinomu.
Warthin-like papillary thyroid carcinoma is a rare variant of papillary carcinoma with a very good prognosis. It is often associated with lymphocytic thyroiditis. Due to its typical histological picture resembling Warthin’s salivary gland tumor, the histological diagnosis is not difficult, usually does not require an accompanying immunohistochemical examination and is based on the presence of nuclear features typical of papillary carcinoma and the presence of oncocytes in a background of rich lymphocyte infiltrate. The preoperative cytologic examination is challenging, as many other lesions may have a similar picture. Women are more likely to get affected. It appears a decade earlier than the classic variant. Clinically, it presents similarly to a conventional papillary carcinoma. In our case report, we would like to present the case of a 56-year-old woman with non-toxic multinodular goiter, in whom the presence of this rare variant of papillary carcinoma was revealed by histological examination.
- MeSH
- adenolymfom chirurgie diagnóza patologie MeSH
- cytodiagnostika metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy * diagnóza patologie MeSH
- papilární karcinom chirurgie diagnóza patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
BACKGROUND: Literature lacks clear evidence regarding the optimal treatment for non-muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies. OBJECTIVE: To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19-64). INTERVENTION: Patients underwent immediate RC versus conservative management with bacillus Calmette-Guérin. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis. RESULTS AND LIMITATIONS: Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study. CONCLUSIONS: Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis. PATIENT SUMMARY: Bacillus Calmette-Guérin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.
- MeSH
- BCG vakcína terapeutické užití MeSH
- cystektomie MeSH
- konzervativní terapie MeSH
- lidé MeSH
- lokální recidiva nádoru patologie MeSH
- nádory močového měchýře * chirurgie patologie MeSH
- papilární karcinom * chirurgie patologie MeSH
- progrese nemoci MeSH
- retrospektivní studie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Pacienti s nesvětlobuněčným renálním karcinomem (non-clear cell renal cell carcinoma, nccRCC) tvoří asi 25 % všech nemocných s primárním zhoubným nádorem ledviny. Otázka standardní systémové léčby nccRCC dosud není dořešena, protože pacienti s touto diagnózou byli vyloučeni z většiny klinických studií a tato klinické jednotka je velice heterogenní. Nejlépe charakterizovanou aberací je aktivační mutace nebo amplifikace mezenchymálně epiteliální tranzice (mesenchymal-epithelial transition, MET), kterou nacházíme u mnoha papilárních renálních karcinomů. Ze srovnání tyrosinkinázových inhibitorů na základě studie fáze II vyplývá, že nejúčinnější monoterapií nccRCC je v současnosti cabozantinib. Řada dalších studií probíhá a budoucnost je i zde pravděpodobně v kombinacích imunoterapie s cílenou léčbou.
Patients with non-clear cell renal cell carcinoma (nccRCC) comprise approximately 25% of all patients with primary renal cell cancer. The standard systemic treatment for nccRCC is not yet established because patients with this diagnosis have been excluded from most clinical trials and nccRCC are a very heterogeneous category that include many clinically and molecularly distinct diseases. The most common aberration is an activating mutation or amplification of MET, which is found in many papillary renal cell carcinomas. A comparative phase II study of tyrosine kinase inhibitors showed that cabozantinib is currently the most effective nccRCC monotherapy. Many other studies are underway, and the future is probably in the combination of immunotherapy with targeted treatment.
Programmed cell death ligand (PD-L1)/PD-1 expression has been studied in a variety of cancers and blockage of PD-L1/PD-1 pathway is a cornerstone of immunotherapy. We studied PD-L1/PD-1 immunohistochemical expression in 47 thyroid gland specimens in groups of (1) Hashimoto thyroiditis (HT) only; (2) HT and follicular epithelial dysplasia (FED); and (3) HT, FED, and papillary thyroid carcinoma (PTC). PD-1 positivity was found in immune cells, namely in lymphocytes, macrophages, and plasma cells with mean values for lymphocytes and macrophages 9% in HT group, 4% in FED group, and 4% in PTC group. PD-L1 positivity was identified in both immune cells and in the normal epithelial cells. In the HT group, mean PD-L1 staining on immune cells was 6%, in FED group 5%, and in PTC group 7%. The mean PD-L1 staining on the epithelial cells in the inflammatory parenchyma was 11.7% in HT, 13.4% in FED, and 8.3% in PTC group. The mean PD-L1 staining of FED foci was 47.2% in FED group and 33.6% in PTC group. The mean tumor proportion score (TPS) was 10.4%, and the mean combined positive score (CPS) was 15.5. At the moment, PTC is not a target of immunotherapy. However, understanding the complex issue of concurrent inflammation and autoimmunity can importantly influence the cancer treatment in future.
The Genitourinary Pathology Society (GUPS) undertook a critical review of the recent advances in bladder neoplasia with a focus on issues relevant to the practicing surgical pathologist for the understanding and effective reporting of bladder cancer, emphasizing particularly on the newly accumulated evidence post-2016 World Health Organization (WHO) classification. The work is presented in 2 manuscripts. Here, in the first, we revisit the nomenclature and classification system used for grading flat and papillary urothelial lesions centering on clinical relevance, and on dilemmas related to application in routine reporting. As patients of noninvasive bladder cancer frequently undergo cystoscopy and biopsy in their typically prolonged clinical course and for surveillance of disease, we discuss morphologies presented in these scenarios which may not have readily applicable diagnostic terms in the WHO classification. The topic of inverted patterns in urothelial neoplasia, particularly when prominent or exclusive, and beyond inverted papilloma has not been addressed formally in the WHO classification. Herein we provide a through review and suggest guidelines for when and how to report such lesions. In promulgating these GUPS recommendations, we aim to provide clarity on the clinical application of these not so uncommon diagnostically challenging situations encountered in routine practice, while also importantly advocating consistent terminology which would inform future work.
BACKGROUND: MicroRNAs (miRNAs) are non-coding regulatory molecules 18-25 nucleotides in length that act as post-transcriptional regulators of gene expression. MiRNAs affect various biological processes including carcinogenesis. Deregulation of miRNAa expression has been described in a variety of tumors including papillary thyroid carcinoma (PTC). The aim of the present study was to investigate the role of selected miRNAs in PTC and find associations between miRNA expression and the BRAF (V600E) mutation. MATERIALS AND METHODS: The study group comprised a total of 62 patients with surgically treated PTC. The control group consisted of 30 patients with nodular goitre that were surgically treated in the same time period. The expression status of miR-146b, miR-181a, miR-187, miR-221 and miR-222 was determined using quantitative real-time PCR. BRAF mutation analysis was performed by PCR with reverse hybridization. RESULTS: MiR-146b, miR-181a, miR-187, miR-221 and miR-222 were up-regulated in PTC compared to normal thyroid gland tissue of the same patient. MiR-146b, miR-187, miR-221 and miR-222 were also up-regulated in PTC compared to nodular goitre. The recurrent tumors were statistically significantly associated with up-regulation of miR-221. The mutation V600E of BRAF gene was significantly associated with up-regulation of miR-146b and with down-regulation of miR-187. CONCLUSION: Over-expression of selected miRNAs in PTC compared to normal thyroid gland tissue and nodular goitre was found. Moreover, miR-221 may serve as a prognostic marker as its over-expression was significantly associated with recurrent tumors.
- MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- mikro RNA * genetika MeSH
- mutace MeSH
- nádory štítné žlázy * genetika MeSH
- papilární karcinom štítné žlázy genetika MeSH
- papilární karcinom * genetika MeSH
- prognóza MeSH
- protoonkogenní proteiny B-raf genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
