Despite considerable interest in the modulation of tumor-associated Foxp3 + regulatory T cells (T regs ) for therapeutic benefit, little is known about the developmental origins of these cells and ...the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific T regs (termed MJ23 T regs ) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 T regs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 T regs underwent autoimmune regulator (Aire)—dependent thymic development in both male and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific T regs , which are likely coopted by tumors developing within the associated organ.
Within this decade, several important updates in prostate cancer have been presented through expert international consensus conferences and influential publications of tumor classification and ...staging.
To present key updates in prostate carcinoma.
The study comprised a review of literature and our experience from routine and consultation practices.
Grade groups, a compression of the Gleason system into clinically meaningful groups relevant in this era of active surveillance and multidisciplinary care management for prostate cancer, have been introduced. Refinements in the Gleason patterns notably result in the contemporarily defined Gleason score 6 cancers having a virtually indolent behavior. Grading of tertiary and minor higher-grade patterns in radical prostatectomy has been clarified. A new classification for prostatic neuroendocrine tumors has been promulgated, and intraductal, microcystic, and pleomorphic giant cell carcinomas have been officially recognized. Reporting the percentage of Gleason pattern 4 in Gleason score 7 cancers has been recommended, and data on the enhanced risk for worse prognosis of cribriform pattern are emerging. In reporting biopsies for active surveillance criteria-based protocols, we outline approaches in special situations, including variances in sampling or submission. The 8th American Joint Commission on Cancer TNM staging for prostate cancer has eliminated pT2 subcategorization and stresses the importance of nonanatomic factors in stage groupings and outcome prediction. As the clinical and pathology practices for prostate cancer continue to evolve, it is of utmost importance that surgical pathologists become fully aware of the new changes and challenges that impact their evaluation of prostatic specimens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The NKX3.1 immunohistochemical stain is widely recognized as a highly sensitive and specific marker for prostate adenocarcinoma. Nevertheless, its expression has been documented in various ...nonprostatic tissues and malignancies. This review aims to provide an overview of NKX3.1 expression in diverse tumor types, with a specific focus on its aberrant expression in esophageal/gastroesophageal adenocarcinoma (E/GE-ADC). In our investigation, we explored the expression of NKX3.1 in a series of E/GE-ADC to shed light on its prevalence in this tumor category. A total of 50 samples, comprising primary and metastatic E/GE-ADC specimens from 34 patients, were subjected to immunohistochemical analysis. Stained sections were scored based on the intensity and distribution-categorized as negative, weak, moderate, or strong in either a focal or diffuse pattern. Strong staining corresponds to the intensity observed in normal prostate controls, while focal and diffuse staining denote <50% and ≥50% of tumor nuclei staining positive, respectively. Our semiquantitative scoring revealed that 6 (12%) of the primary and metastatic E/GE-ADC specimens exhibited variable positivity for NKX3.1. This finding suggests that E/GE-ADC can sporadically stain positive for NKX3.1, introducing potential challenges in definitively determining the primary site of origin in certain clinical scenarios. Along with a literature review of NKX3.1 expression in other tumor types, our study provides additional important information about the extent to which this immunostain can be seen in E/GE-ADCs, which, to our knowledge, has not been reported.
Introduction
ISUP Grade Group 1 prostate cancer is the lowest histologic grade of prostate cancer with a clinically indolent course. Removal of the term ‘cancer’ has been proposed and has historical ...precedent both in urothelial and thyroid carcinoma.
Methods
Evidence-based review identifying arguments for and against Grade Group 1 being referred to as cancer.
Results
Grade Group 1 has histologic evidence of tissue microinvasion and 0.3–3% rate of extraprostatic extension. Genomic evaluation suggests overlap of a minority of Grade Group 1 cancers with those of Grade Group 2. Conversely, Grade Group 1 tumors appear to have distinct genetic and genomic profiles from Grade Group 3 or higher tumors. Grade Group 1 has no documented ability for regional or distant metastasis and long-term follow up after treatment or active surveillance is safe with excellent oncologic outcomes.
Discussion
Grade Group 1 prostate cancer, while showing evidence of neoplasia on histology has a remarkably indolent natural history more akin to non-neoplastic precursor lesions. Consideration should be given to renaming Grade Group 1 prostate cancer, which has the potential to minimize overtreatment, treatment-related side effects, patient anxiety, and financial burden on the healthcare system.
Genetic analysis of advanced cancer is limited by availability of representative tissue. Biopsies of prostate cancer metastasized to bone are invasive with low quantity of tumor tissue. The prostate ...cancer genome is dynamic, however, with temporal heterogeneity requiring repeated evaluation as the disease evolves. Circulating tumor cells (CTCs) offer an alternative, "liquid biopsy", though single CTC sequencing efforts are laborious with high failure rates.
We performed exome sequencing of matched treatment-naïve tumor tissue, castrate resistant tumor tissue, and pooled CTC samples, and compared mutations identified in each.
Thirty-seven percent of CTC mutations were private to CTCs, one mutation was shared with treatment-naïve disease alone, and 62% of mutations were shared with castrate-resistant disease, either alone or with treatment-naïve disease. An acquired nonsense mutation in the Retinoblastoma gene, which is associated with progression to small cell cancer, was identified in castrate resistant and CTC samples, but not treatment-naïve disease. This timecourse correlated with the tumor acquiring neuroendocrine features and a change to neuroendocrine-specific therapy.
These data support the use of pooled CTCs to facilitate the genetic analysis of late stage prostate cancer.
Purpose
To provide a comprehensive update of the joint consultation of the International Consultation on Urological Diseases (ICUD) for the diagnosis and management of non-urothelial cancer of the ...urinary bladder.
Methods
A detailed analysis of the literature was conducted reporting on the epidemiology, etiology, diagnosis, treatment and outcomes of non-urothelial cancer of the urinary bladder. An international, multidisciplinary expert committee evaluated and graded the evidence according to the Oxford System of Evidence-based Medicine modified by the ICUD.
Results
The major non-urothelial cancers of the urinary bladder are squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. Several other non-urothelial tumors are rare but important to identify because of their aggressive behavior when compared to urothelial bladder tumors. Radical cystectomy and urinary diversion, preceded by neoadjuvant radiation or chemotherapy in some of these tumors, is the main method or treatment for resectable disease. Adjuvant therapy is not usually successful and no novel targeted or immunotherapeutic agents have been identified to provide benefit. Patients with small cell neuroendocrine tumors of the bladder should be offered chemotherapy before surgery. Because non-urothelial cancers are usually locally advanced and/or metastatic at the time of diagnosis, 5-year survival is generally poor.
Conclusions
Non-urothelial cancers of the urinary bladder are rare and mostly lack established protocols for treatment. The prognosis of most of these tumors is poor because they are usually advanced at the time of diagnosis. A multimodal treatment approach should be considered to improve outcomes.
Reply to M. Baboudjian et al Eggener, Scott E; Berlin, Alejandro; Vickers, Andrew J ...
Journal of clinical oncology,
2023-Mar-01, 2023-03-01, 20230301, Letnik:
41, Številka:
7
Journal Article
Classification of the putative flat preneoplastic and neoplastic lesions of the urothelium with features subthreshold for urothelial carcinoma in situ remains a challenging, indeed, vexing problem in ...diagnostic surgical pathology. This area, subtending lesions including flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance, has struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. Herein, we review the state of the literature around these lesions, reviewing contemporary criteria and definitions, assessing the arguments in favor and against of retaining hyperplasia, dysplasia, and atypia of unknown significance as diagnostic entities. We clarify the intent of the original definitions for dysplasia as a lesion felt to be clearly neoplastic but with morphologic features that fall short of the threshold of urothelial carcinoma in situ. While several pathologists, including some experts in the field, conflate the term dysplasia with urothelial atypia of unknown significance, the latter is defined as a descriptive diagnosis term to express diagnostic uncertainty of a lesion of whether it is clearly reactive or neoplastic. Both molecular studies and clinical needs are considered, as we outline our approach on diagnosing each of these lesions in clinical practice. Recommendations are made to guide consistency and interoperability in future scholarship, and the place of these lesions in context of evolving trends in the field is considered.
Although well recognized in the literature, the contemporary clinicopathologic data regarding choriocarcinoma (CC) as a pure or the predominant component of a testicular germ cell tumor (GCT) are ...limited. Herein, we present a series of pure CC and predominant CC in mixed GCT of the testis obtained from a single oncology institution. A comprehensive histologic review of 1010 orchiectomies from 1999 to 2011 yielded 6 (0.6%) pure CC and 9 (0.9%) mixed GCT cases with a predominant CC component. Patients’ ages ranged from 20 to 39 years (median 29 y). All patients had markedly elevated serum β-hCG levels (median 199,000 IU/mL) at presentation. All tumors were unilateral and involved the right (9/15) and left (6/15) testis. The mean tumor size was 6.5 cm (range, 1.5 to 8 cm). Histology was similar for pure CCs and the CC component of mixed GCTs. CC commonly showed expansile hemorrhagic nodular cysts surrounded by variable layers of neoplastic trophoblastic cells (mononucleated trophoblasts and syncytiotrophoblasts). The syncytiotrophoblasts usually covered columns of mononucleated trophoblasts and occasionally formed plexiform aggregates and pseudovillous protrusions. Immunohistochemical stains suggested a mixture of cytotrophoblasts (p63, HPL) and intermediate trophoblasts (p63, HPL weak +/−) in the columns of mononucleated cells. In the 9 mixed GCTs, CC comprised 50% to 95% (7/9 were ≥80% CC) of the tumor; 7 were combined with 1, and 2 were combined with 2 other GCT components. The non-CC components included teratoma (5/9), seminoma (2/9), yolk sac tumor (2/9), and embryonal carcinoma (2/9). Lymphovascular invasion, spermatic cord invasion, and tunica vaginalis invasion were present in 15/15, 5/15, and 1/12 cases, respectively. In mixed GCTs, these locally aggressive features were attributed to the CC component, except in 1 tumor in which it was also exhibited by the embryonal carcinoma component. Lymphovascular invasion was multifocal to widespread in 73% of tumors. The stages of the 15 tumors werepT2 (10), pT3 (5); NX (1), N1 (4), N2 (5), N3 (5); and M1a (2) and M1b (13). Distant organ metastasis mostly involved the lungs (11) and liver (10). Follow-up information was available in 14 patients, all of whom received cisplatin-based chemotherapy. All 6 pure CC patients were dead of disease (range, 6 to 14 mo, median 9.5 mo). Follow-up of 8 patients with predominant CC (range, 10 to 72 mo, median 27 mo) showed that 5 died of the disease, and 1 was alive with disease and 2 were alive with no evidence of disease at 60 and 72 months of follow-up, respectively; these latter 2 patients were the only ones with M1a disease on presentation. This series confirms the proclivity for high-stage presentation including presence of distant metastasis, hematogenous spread, and poor outcome of testicular CC. Mixed GCT with a predominant CC component has similar tendency for high-stage presentation, marked elevation of serum β-hCG levels, and aggressive behavior compared with pure CC. This study also showed that distant metastasis by CC when only involving the lungs (M1a) may not be uniformly fatal with chemotherapy. The mononucleated trophoblastic columns in testicular CC appear to be a mixture of cytotrophoblasts and intermediate trophoblasts, similar to that described in gestational CC.
Lower incidence and mortality rates from prostate cancer (PCa) have been shown in Asian men in general compared to Westerners. This is the first study detailing the clinicopathologic features of ...resected prostate cancer in Filipino men living in the Philippines (PH). This study investigated the supposed "lower risk" Filipino and "higher risk" American PCa patients from the PH and the United States of America (USA), respectively. We examined 348 (176 from PH, 172 from USA) radical prostatectomy cases. The clinicopathologic features of both groups (age at time of diagnosis, preoperative prostate-specific antigen pre-op PSA level, Gleason score GS, Grade groups GG, margin involvement, extraprostatic extension EPE, seminal vesicle invasion SVI, and regional lymph node RLN metastasis) were compared. Six of seven prognosticators examined were more strongly associated with Filipinos than with Americans. Filipinos were older at diagnosis (PH: 64.32 ± 6.56 years vs USA: 58.98 ± 8.08 years) and had higher pre-op PSA levels (PH: 21.39 ± 46.40 ng ml−1 vs USA: 7.63 ± 9.19 ng ml−1). Filipino men had more advanced grade, GG 2 with minor pattern 5 (PH: 6.2% vs USA: 2.9%) and GG 5 (PH: 14.8% vs USA: 3.5%). Likewise, other adverse pathological features in margin positivity (PH: 52.3% vs USA: 23.8%), focal EPE (PH: 14.2% vs USA: 2.3%), and SVI (PH: 17.1% vs USA: 5.8%) were more commonly observed in Filipinos. This study reveals the prognostic disadvantage of Filipinos versus Americans and highlights an important difference of Filipinos from other studied Asian ethnicities that have repeatedly been shown to have lower-risk PCa. This study, the first on Filipino PCa patients with RP, suggests the need to modify Western-based risk stratification when employed in other countries like the PH.
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