The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial ...carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (
P
= 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (
P
= 0.008) and cancer-specific survival (
P
= 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.
We report on the clinicopathologic features of 115 cases of high-grade urothelial carcinoma of the upper urinary tract with variant histology present in 39 (34%). Variant histology was typically seen ...in high pathological stage (pT2-pT4) (82%, 32 cases) patients with lower survival rate (70%, 27 cases, median survival 31 months) and consisted in urothelial with one (23%), two (3%), and three or more variants (3%); 4% of cases presented with pure variant histology. Squamous divergent differentiation was the most common variant (7%) followed by sarcomatoid (6%) and glandular (4%), followed by 3% each of micropapillary, diffuse-plasmacytoid, inverted growth, clear cell glycogenic, or lipid-rich. The pseudo-angiosarcomatous variant is seen in 2%, and 1% each of nested, giant-cell, lymphoepithelioma-like, small-cell, trophoblastic, rhabdoid, microcystic, lymphoid-rich stroma, or myxoid stroma/chordoid completed the study series. Loss of mismatch repair protein expression was identified in one case of upper urinary tract carcinoma with inverted growth variant (3.6%). Variant histology was associated to pathological stage (
p
= 0.007) and survival status (
p
= 0.039). The univariate survival analysis identified variant histology as a feature of lower recurrence-free survival (
p
= 0.046). Our findings suggest that variant histology is a feature of aggressiveness in urothelial carcinoma of the upper urinary tract worth it to be reported.
Aims
To verify the applicability, reproducibility and predictive value of a proposed unified classification (amended Ljubljana classification) for laryngeal squamous intraepithelial lesions (SILs).
...Methods and results
Six internationally recognized experts and three pathologists from Ljubljana contributed to this study by evaluating a set of laryngeal SILs using the new system: low‐grade SIL, high‐grade SIL, and carcinoma in situ (CIS). The overall agreement among reviewers was good. Overall unweighted and weighted κ‐values and 95% confidence intervals were 0.75 (0.65–0.84) and 0.80 (0.71–0.87), respectively. The results were stratified between the international reviewers and the Ljubljana pathologists. The former had good overall agreement, and the latter had very good agreement. Kaplan–Meier survival curves showed a significant difference (P < 0.0001) between patients with low‐grade and high‐grade SILs; 19 of 1204 patients with low‐grade SILs and 30 of 240 patients with high‐grade SILs progressed to malignancy in 2–15 years and in 2–26 years, respectively.
Conclusions
The proposed modification to the Ljubljana classification provides clear morphological criteria for defining the prognostic groups. The criteria facilitate better interobserver agreement than previous systems, and the retrospective follow‐up study demonstrates a highly significant difference in the risk of malignant progression between low‐grade and high‐grade SILs.
Nonsurgical therapeutic options for prostatic diseases are divided into androgen action-related, with androgen action inhibition (AAI), or androgen action-unrelated strategies, such as radiotherapy ...(RT). AAI, achieved by numerous medications with antiandrogen activity, is used for prostatic hyperplasia and carcinoma. Treatment mostly affects secretory epithelial cells, with consequent reduction in prostate volume and diminished amount of cancer. Histologically, AAI changes the morphologic appearance of benign prostatic glands, prostatic intraepithelial neoplasia, and cancer, as well as prostatic stroma. The effects of most AAI drugs are similar, although variable in intensity. Expression of some diagnostic immunohistochemical markers can decline after longtime treatment, requiring careful interpretation of staining results. Patterns of tissue injury after RT for prostate cancer differ from those after AAI. While irradiation has a profound effect on benign prostatic glands, it does not affect immunohistochemistry, which retains its diagnostic value. In order to make a reliable diagnosis in needle biopsies of treated prostate cancer, uropathologists should have all the relevant information on treatment modalities and their duration. As treatment affects the morphology of prostate cancer, Gleason grading is unreliable and therefore not recommended. An overview of treatment effects caused by AAI and RT is herein presented, with discussion on their importance in everyday practice.
Basal cell carcinoma of the prostate is rare. Usually, it is diagnosed in elderly men with nocturia, urgency, lower urinary tract obstruction and normal PSA.
We report on a case of a 56-years-old ...patient who presented at the emergency ward with weight loss, nausea and vomiting. The diagnostic evaluation showed acute renal failure due to a bladder tumor. After admission to the urology ward and subsequent contrast-enhanced CT urography and contrast-enhanced chest CT, a non-metastatic bladder tumor that infiltrated the right side of the bladder and seminal vesicles was found. High-grade muscle-invasive urothelial carcinoma was diagnosed from TURBT specimens, followed by radical cystoprostatectomy with pelvic lymphadenectomy and formation of ureterocutaneostomy sec. Bricker. The histopathological examination of the resection specimen surprisingly revealed the presence of prostatic basal cell carcinoma pT4N0M0 and not urothelial cancer. Due to renal failure, the patient required hemodialysis. The recommendation of the multidisciplinary oncological meeting was to follow up with the patient by the surgeon-urologist. On imaging six months after surgery, it was suspicious for recurrence. Patient was considered for adjuvant oncological treatment.
Although rare, basal cell carcinoma of the prostate should be considered in patients with lower urinary tract symptoms, hematuria and normal PSA. Transurethral resection of bladder tumor is indicated in patients presenting with hematuria and bladder tumor. In evaluation of such cases rare histological types should be included in the differential diagnosis.
Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical ...prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In this study, we investigated the prognostic potential of DNA ploidy.
Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was measured and a Ploidy Score (PS) was generated.
Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time (PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant (p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence free survival within CAPRA-S low-risk cohort.
DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments.
Focal or non-focal/extensive extraprostatic extension of prostate carcinoma is an important pathologic prognostic parameter to be reported after radical prostatectomy. Currently, there is no ...agreement on how to measure and what are the best cutoff points to be used in practice. We hypothesized that digital microscopy would potentially provide more objective measurements of extraprostatic extension, thus better defining its clinical significance. To further our knowledge on digital prostate pathology, we evaluated the status of extraprostatic extension in 107 consecutive laparoscopic radical prostatectomy samples, using digital and conventional light microscopy. Mean linear and radial measurements of extraprostatic extension by digital microscopy significantly correlated to pT status (
p
= 0.022 and
p
= 0.050, respectively) but only radial measurements correlated to biochemical recurrence (
p
= 0.042) and grade groups (
p
= 0.022). None of the measurements, whether conventional or digital, were associated with lymph node status. Receiving operating characteristic analysis showed a potential cutoff point to assess linear measurements by conventional (< vs. > 24.21 mm) or digital microscopy (< vs. > 15 mm) or by radial measurement (< vs. > 1.6 mm). Finally, we observed an association between the number of paraffin blocks bearing EPE with pT (
p
= 0.041) status (digital microscopy), and linear measurements by conventional (
p
= 0.044) or digital microscopy (
p
= 0.045) with lymph node status. Reporting EPE measurements by digital microscopy, both linear and radial, and the number of paraffin blocks with EPE, might provide additional prognostic features after radical prostatectomy.
PURPOSEProstate cancer (PCa) with biopsy-based grade group (GG) 1 or 2 characteristics has a favorable outcome, yet some cases still progress after radical prostatectomy and present with biochemical ...recurrence (BCR). We hypothesized that the multi-scale tissue architecture (MSTA) analysis score would correlate with the aggressive PCa phenotype and could be used as a tool for risk assessment to improve the management of patients with favorable-risk PCa. MATERIALS AND METHODSMSTA was evaluated in needle-biopsy samples from 115 patients with favorable-risk PCa, as defined by GG1 and GG2, a prostate-specific antigen (PSA) level of <10 ng/mL, a clinical stage of cT1c to cT2b, and general Gleason GG (GGG) and expert pathologist-assessed GG (EGG). Algorithms based on Voronoi diagrams were applied to all Feulgen-thionin-stained diagnostic areas. One hundred tissue architecture features were calculated and an MSTA score, a linear combination of the most discriminant features, was generated. Correlation of MSTA score with BCR and other clinical variables was investigated. RESULTSIn a univariate regression model, EGG, clinical stage, and MSTA were significant predictors of BCR (respective p-values: 0.0016, 0.016, and 0.028). Survival analysis showed that patients with a high MSTA score were more likely to experience BCR than were patients with a low MSTA score (odds ratio, 2.9). Combining MSTA with GG assessment resulted in a significant stratification of risk for BCR. CONCLUSIONSMSTA score could be used as an objective adjunct risk stratification tool to pathologist assessments and could improve the management of patients with favorable-risk PCa.
Drugs for the treatment of depressive disorders, including SNRIs (serotonin noradrenaline reuptake inhibitors) venlafaxine and duloxetine, are widely prescribed as they have a high therapeutic to ...toxicity ratio. In rare cases, adverse effects may be severe, usually due to iatrogenic, accidental or intentional self-overdose that cause the excessive accumulation of serotonin and noradrenaline in synaptic clefts. Lethal intoxication with a combination of venlafaxine and duloxetine (postmortem blood concentrations 24 mg/L and 0.97 mg/L, respectively) without co-ingested substances, comorbidities or injuries that could have an unknown contribution to a fatal outcome is presented for the first time in the following case report, with a comprehensive clinical history, and complete results of the performed analyses. The cause of death was a serotonin syndrome that progressed to death in approximately six hours and 15 min after the suicidal ingestion of venlafaxine and duloxetine. Despite the high therapeutic to toxicity ratio SNRIs, which are reserved for patients with severe forms of depressive disorders and a higher suicidal tendency, they should be cautiously prescribed and handed over in smaller packages to make them easier to follow, and thus avoid accumulation within the patient’s reach.
Positive surgical margin (PSM) extension reported as focal or non-focal/extensive is an important pathologic prognostic parameter after radical prostatectomy. Likewise, there is limited or no ...agreement on how to measure and what the best cut-off points to be used in practice are. We hypothesized that digital microscopy (DM) would potentially provide a more objective way to measure PSM and better define its clinical significance. To further our knowledge, we have evaluated PSM status in 107 laparoscopic radical prostatectomies using digital and conventional light microscopy (LM). DM evaluation detected three additional PSM cases, but no differences were seen (LM vs DM;
p
= 0.220). Mean linear measurement correlated to biochemical recurrence (BR) (LM,
p
= 0.002; DM,
p
= 0.001). ROC analysis identified a cut-off point to assess linear measurement by LM (3.5 mm) or DM (3.2 mm), but only digital measurement was significant for BR-free survival. Our study also evaluated a cut-off ≤ 3 mm that was associated to BR using LM (
p
= 0.023) or DM (
p
= 0.001). Finally, the number of paraffin blocks bearing PSM correlated with BR (
p
< 0.001) status with either LM or DM. In conclusion, DM produces similar data than LM but shows more accurate measurements. Reporting of PSM with score of ≤ 3 vs. > 3 mm linear extent using LM (3.2 mm if digital microscopy is applied) might represent an important prognostic feature after radical prostatectomy. Alternatively, reporting the number of blocks with PSM 1 vs. 2 or more might also provide important prognostic data in practice.
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