A comparative study of AJCC and the modified staging system in pT2/pT3 penile squamous cell carcinoma - a validation on an external data set.

AIMS: The recent changes in the American Joint Commission on Cancer, 8th edition (AJCC-8E) pT2 and pT3 tumour definitions for penile cancer need robust validation studies. A recent study redefined and modified the pT2 and pT3 stages incorporating the histopathological variables (tumour grade, lymphovascular invasion, perineural invasion) similar to that used in the current AJCC-8E pT1 stage tumour subclassification. In this study, we validate and compare this proposed staging with the AJCC staging systems on an external data set. METHODS AND RESULTS: The data set from a previously published study was obtained. pT2 and pT3 stages were reconstructed as per AJCC 7th edition (AJCC-7E), AJCC-8E and the proposed staging. The staging systems were correlated with nodal metastasis, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). All systems were compared using receiver operating characteristic (ROC) curves. A total of 281 cases formed the study cohort. AJCC-8E (P = 0.031) and the proposed staging (P = 0.003) correlated with nodal metastasis on adjusted analysis, the latter with a better strength of association (AJCC-8E, γ = -0.471; proposed, γ = -0.625). On adjusted analysis, all the staging systems had a significant correlation with DFS, while only AJCC-8E and the proposed staging correlated with CSS and OS. On ROC curve analysis, the proposed staging had the highest area under the curve and was the only staging system to statistically correlate with all the outcome variables. CONCLUSIONS: The proposed staging for pT2/pT3 tumour stages in penile cancer may improve the prognostic and predictive ability.

Comparison of a modified staging system with 8th edition AJCC criteria in a North American cohort of pT2/pT3 HPV-negative penile squamous cell carcinoma.

The staging for pT2/pT3 penile squamous cell carcinoma (pSCC) has undergone major changes. Some authors proposed criteria wherein the distinction between pT2/pT3 was made using the same histopathological variables that are currently utilized to differentiate pT1a/pT1b. In this single-institution, North American study, we focused on (HPV-negative) pT2/3 pSCCs (i.e., tumors invading corpus spongiosum/corpus cavernosum), and compared the prognostic ability of the following systems: (i) AJCC (8th edition) criteria; (ii) modified staging criteria proposed by Sali et al. (Am J Surg Pathol. 2020; 44:1112-7). In the proposed system, pT2 tumors were defined as those devoid of lymphovascular invasion (LVI) or perineural invasion (PNI), and were not poorly differentiated; whereas pT3 showed one or more of the following: LVI, PNI, and/or grade 3. 48 pT2/pT3 cases were included (AJCC, pT2: 27 and pT3: 21; Proposed, pT2: 22 and pT3: 26). The disease-free survival (DFS) and progression-free survival (PFS) did not differ between pT2 and pT3, following the current AJCC definitions (p = 0.19 and p = 0.10, respectively). When the pT2/3 stages were reconstructed using the modified criteria, however, a statistically significant difference was present in both DFS and PFS between pT2 and pT3 (p = 0.004 and p = 0.003, respectively). The proposed staging system has the potential to improve the prognostication of pT2/pT3 tumors in pSCC. Each of these histopathologic variables has been shown to have a significant association with outcomes in pSCC, which is an advantage. Further studies are needed to demonstrate the utility of this modified staging system in patient populations from other geographic regions.

Updates in staging of penile cancer: the evolution, nuances, and issues.

Staging based on the tumor (T), node (N), and metastasis (M) schema of the American Joint Committee on Cancer (AJCC) is usually the most important prognostic factor for any tumor type. Although a rare tumor, in penile cancers, this staging has evolved rapidly in the last two editions of the AJCC Cancer Staging manuals. These changes and updates are largely based on the advancement in our knowledge of the complex anatomy of the penis, the role of histopathological variables in disease biology, and the results of multicentric studies comprising large data sets. In this review, we present the evolution of the AJCC staging model from its inception to the present day. The evidence and data that entailed these changes are also discussed. We highlight a few issues with the current staging model and also briefly discuss the future perspectives and the road map which, with the help of global efforts, can further refine the staging models.

Predictors of Pelvic Lymph Nodal Metastasis in Penile Squamous Cell Carcinoma- Results From a Matched-Pair Analysis.

INTRODUCTION: Pelvic lymph node (PLN) metastasis has a worse prognosis in penile squamous cell carcinoma. This study sought to determine the predictors of PLN metastasis in penile SCC. MATERIALS AND METHODS: This retrospective study included primary penile resections with inguinal lymph nodes (ILN) and PLN dissections over 10 years (2007-2017). A subset of treatment naïve cases with PLN metastasis was matched for age and tumor size with another subset of cases having metastatic ILN and negative PLN. The variables were correlated with the PLN metastasis using appropriate statistical tests. Internal validation of the multivariate model was conducted by using 2000 bootstraps on the same cohort. The optimum cut-off for the number of positive ILN was obtained by plotting a receiver operating characteristic curve and using the highest Youden's index as a discriminator. RESULTS: A total of 56 cases (28 in each subset) formed the study cohort. On unadjusted analysis the size of the largest ILN (p=0.038), number of positive ILN (p=0.001), percentage of positive ILN (p=0.001), and laterality of ILN involvement (p=0.007) had a significant correlation with PLN metastasis. On adjusted analysis, the number of positive ILN (p=0.011) was the only statistically significant variable. Bootstrapping results indicated that this multivariate model represented the dataset adequately. The maximum Youden's index was obtained when ≥5 ILN were positive. CONCLUSIONS: The number of metastatic ILN is the most important predictor of PLN metastasis. A higher threshold of metastatic ILN for addressing PLN dissection can be investigated, particularly in a high disease burden setup.

Ectopic Prostate Tissue Presenting as Urinary Bladder Tumor: The Imitation Game!

Ectopic prostate tissue is a rare phenomenon. Histologically and immunohistochemically it is indistinguishable from normal prostatic tissue but it is difficult to recognize and may be confused with malignancy when presenting as ectopic lesion in the urinary system. Therefore, awareness of this entity is essential for both urologists and pathologists to prevent misdiagnosis.

Validation of Whole Slide Imaging for primary surgical pathology diagnosis of prostate biopsies.

CONTEXT: Whole slide imaging (WSI) is an important component of digital pathology which includes digitization of glass slides and their storage as digital images. Implementation of WSI for primary surgical pathology diagnosis is evolving, following various studies which have evaluated the feasibility of WSI technology for primary diagnosis. AIMS, SETTINGS AND DESIGN: The present study was a single-center, observational study which included evaluation by three pathologists and aimed at assessing concordance on specialty-specific diagnosis and comparison of time taken for diagnosis on WSI and conventional light microscopy (CLM). MATERIALS AND METHODS: Seventy prostate core biopsy slides (reported between January 2016 and December 2016) were scanned using Pannoramic MIDI II scanner, 3DHISTECH, Budapest, Hungary, at 20× and 40×. Sixty slides were used for validation study following training with 10 slides. STATISTICAL ANALYSIS USED: Intraobserver concordance for diagnosis between the two platforms of evaluation was analyzed using Cohen's κ statistics and intraclass correlation coefficient (ICC); observation time for diagnosis was compared by Wilcoxon signed-rank test. RESULTS: Interpretation on WSI using 20× and 40× was comparable with no major discordance. A high level of intraobserver agreement was observed between CLM and WSI for all three observers, both for primary diagnosis (κ = 0.9) and Grade group (κ = 0.7-0.8) in cases of prostatic adenocarcinoma. The major discordance rate between CLM and WSI was 3.3%-8.3%, which reflected the expertise of the observers. The time spent for diagnosis using WSI was variable for the three pathologists. CONCLUSION: WSI is comparable to CLM and can be safely incorporated for primary histological diagnosis of prostate core biopsies.

A Modified Histopathologic Staging in Penile Squamous Cell Carcinoma Predicts Nodal Metastasis and Outcome Better Than the Current AJCC Staging.

Recently, the American Joint Committee on Cancer (AJCC) updated the staging system for penile squamous cell carcinoma. According to it, unlike its previous version, the involvement of urethra does not upstage the tumor; however, the involvement of corpora cavernosa (CC) does. The tumors involving CC are now staged pT3, whereas those involving corpora spongiosa (CS) are staged pT2, irrespective of the involvement of the urethra. In the current study, we sought to validate these recent modifications and in-process also attempted to improvise upon it. The histopathology slides were reviewed in 142 cases of penile squamous cell carcinoma. The histopathologic variables noted were tumor grade, anatomic level of invasion (CC/CS), lymphovascular invasion (LVI), and perineural invasion (PNI). Metastases to the lymph nodes were confirmed. Tumors were staged pT2/pT3 according to AJCC 8th edition and this staging system was further improvised by incorporating histopathologic variables similar to pT1 tumors in AJCC 8th edition. Accordingly, pT2 tumors invaded CS/CC without LVI or PNI and were not grade 3, whereas pT3 tumors invaded CS/CC, showed LVI and/or PNI, or were grade 3. Both the staging models were then correlated with nodal metastasis and disease-free survival. The new staging model (P=0.001) and not the AJCC pT2/pT3 stages (P=0.2) showed a statistically significant correlation with nodal metastasis. Similarly, only the proposed model significantly impacted disease-free survival (P=0.011). To conclude, we were unable to validate the prognostic difference between the pT2/pT3 stages according to AJCC 8th edition. The staging system can be improvised by incorporating histopathologic variables similar to pT1 tumors.

Identification of Luminal Subtypes of Breast Carcinoma Using Surrogate Immunohistochemical Markers and Ascertaining Their Prognostic Relevance.

BACKGROUND: Therapeutic decisions in breast carcinoma are being made on the basis of tumor cell proliferation using exorbitant genomic tests. The 2013 St Gallen meeting advocated surrogate definitions for classifying tumors into luminal subtypes on the basis of immunohistochemical (IHC) markers. We studied the classification of estrogen receptor (ER)-positive tumors using these definitions as well as different methods for Ki-67 labeling index (LI) estimation. PATIENTS AND METHODS: A total of 541 ER+ invasive breast carcinoma cases from January 2012 to December 2012 were evaluated for Ki-67 LI by the average and hot spot methods. The IHC results of ER, PR, and human epidermal growth factor receptor 2 (HER2) were noted. HER2 IHC equivocal (2+) samples were subjected to HER2 fluorescence in-situ hybridization testing. Luminal subgroups created on the basis of the 2013 St Gallen meeting guidelines were correlated with clinicopathologic variables and disease-free survival. RESULTS: The distribution of luminal subtypes was as follows: luminal A-like, 13.3%; luminal B-like (HER2-), 57.9%; and luminal B-like (HER2+), 28.8%. Approximately 6% of cases were recategorized into different subgroups when the average method was used instead of the hot spot method for Ki-67 LI assessment. Younger patients (≤ 50 years), grade 3 tumors, positive axillary nodes, recurrence, and distant metastasis had a positive statistical correlation with luminal B-like (HER2-) subtype. Patients with luminal B-like (HER2-) tumors had a shorter disease-free survival compared to patients with luminal A-like tumors. CONCLUSION: Ki-67 LI, irrespective of the method of assessment, along with PR, can be efficiently used to divide ER+ tumors into prognostic subgroups in Indian patients.

Histopathological risk scoring system as a tool for predicting lymph nodal metastasis in penile squamous cell carcinoma.

Penile cancer is an aggressive neoplasm and nodal metastasis is a key factor in determining the outcome. While there is a paucity of tools predicting nodal metastasis, an elective groin node dissection (GND) may cause severe morbidity. We aimed to devise a histopathology-based risk stratification system to predict the risk of nodal metastasis in penile squamous cell carcinoma (SCC) patients. In this retrospective clinicopathological analysis, consecutive penile SCC patients who had undergone primary surgical treatment with GND from 2007 to 2012 were included. Histopathology slides were reviewed and a histopathological risk scoring system (ranging from 3 to 9) was devised by adding the values assigned to the following pathological variables: tumour grade (1-3); anatomical level of infiltration (1-3); and tumour infiltration pattern (1-3). Three risk groups were created based on histopathological risk scores. Final scores and risk groups were correlated with nodal metastasis, disease-free survival (DFS) and overall survival (OS). We also validated the earlier described prognostic index score (PIS) on our set of patients and compared it to our proposed scoring system. A total of 162 cases of primary penile resections with unilateral or bilateral groin node dissection were identified during the study period. Sixty-two of 68 patients (91.17%) and 58 of 94 patients (61.7%) had nodal metastasis on upfront and follow-up nodal basin surgeries, respectively. Chances of nodal metastasis for each risk group were as follows: low risk (score 3 and 4) 14.3%; intermediate risk (score 5) 52.6%; and high risk (scores 6-9) 83.7%. Follow-up was available in 145 patients (89.5%). Median follow-up was 21 months (1-96 months). The histopathological scoring system (p=0.04) and risk groups (p=0.005) had a statistically significant correlation with DFS but not with OS. Logistic regression model demonstrated that this stratification system was a good predictor of nodal metastasis. Further, this scoring system had better predictive sensitivity for detecting true node-negative cases and marginally better accuracy in detecting nodal metastasis as compared to the PIS. Our study demonstrates that the histopathological risk stratification can predict nodal metastasis and aid in planning management of penile cancer patients with judicious implementation of the morbid procedure of GND.