Advances, recognition, and interpretation of molecular heterogeneity among conventional and subtype histology of urothelial carcinoma (UC): a survey among urologic pathologists and comprehensive review of the literature.

AIMS: Urothelial carcinoma (UC) demonstrates significant molecular and histologic heterogeneity. The WHO 2022 classification has hinted at adding molecular signatures to the morphologic diagnosis. As morphology and associated molecular repertoire may potentially translate to choices of and response to therapy and relapse rate, broader acceptability of recognizing these key features among uropathologists is needed. This prompted an international survey to ascertain the practice patterns in classical/subtype UC among uropathologists across the globe. METHODS AND RESULTS: A survey instrument was shared among 98 uropathologists using SurveyMonkey software. Anonymized respondent data were analysed. The response rate was 85%. A majority were in concordance with the profiles of luminal (93%) and basal (82%) types. Opinion on the FGFR3 testing platform was variable. While 95% concurred that TERT promoter mutation is the key driver in UC, 72% had the opinion that APOBEC mutagenesis is the main signature in muscle invasive bladder cancer (MIBC). Uropathologists have divergent opinions on MIBC and ERCC2 mutations. Among the participants, 94% would quantify aggressive micropapillary and sarcomatoid histology, while 88% would reevaluate another transurethral resection of the bladder tumour specimen in nonmuscle invasive tumour with micropapillary, small cell, or sarcomatoid histology. A leading number agreed to specific molecular signatures of micropapillary (93%), plasmacytoid (97%), and small cell (86%) subtypes. Ninety-six percent of participants agreed that a small-cell component portends a more aggressive course and should be treated with neoadjuvant chemotherapy and 63% would perform HER2/neu testing only on oncologist's request in advanced tumours. Ninety percent agreed that microsatellite instability testing, although not a standard protocol, should be considered in young patients with upper tract UC. Eighty-six percent agreed that UC with high tumour mutational burden would be a better candidate for immunotherapy. CONCLUSION: In the era of precision medicine, enhanced understanding of molecular heterogeneity of UC will contribute to better therapeutic options, novel biomarker discovery, innovative management protocols, and outcomes. Our survey provides a broad perspective of pathologists' perceptions and experience regarding incorporation of histomolecular approaches to "personalize" therapy. Due to variable clinical adoption, there is a need for additional data using uniform study criteria. This will drive generation of best practice guidelines in this area for widespread and consistent clinical utility.

Pathophysiology of Spinal Cord Injury and Tissue Engineering Approach for Its Neuronal Regeneration: Current Status and Future Prospects.

A spinal cord injury (SCI) is a very debilitating condition causing loss of sensory and motor function as well as multiple organ failures. Current therapeutic options like surgery and pharmacotherapy show positive results but are incapable of providing a complete cure for chronic SCI symptoms. Tissue engineering, including neuroprotective or growth factors, stem cells, and biomaterial scaffolds, grabs attention because of their potential for regeneration and ability to bridge the gap in the injured spinal cord (SC). Preclinical studies with tissue engineering showed functional recovery and neurorestorative effects. Few clinical trials show the safety and efficacy of the tissue engineering approach. However, more studies should be carried out for potential treatment modalities. In this review, we summarize the pathophysiology of SCI and its current treatment modalities, including surgical, pharmacological, and tissue engineering approaches following SCI in preclinical and clinical phases.

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.

Phyllodes Tumor as a Secondary Neoplasm in Survivors of Childhood Cancer: A Tertiary Care Cancer Centre Experience.

Secondary neoplasms (SNs) are being increasingly identified in long-term survivors of childhood cancer. Phyllodes tumor (PT) form a distinctly uncommon SN. We report a series of 6 female childhood cancer survivors who developed PT as SN. The median age at primary diagnosis was 13 years. Their primary tumors were bone sarcoma (4) and acute leukemia (2), and all were treated with chemotherapy, predominantly with alkylating agents and/or anthracyclines. None had received direct radiotherapy to the chest wall. Subsequently, PT were detected after a median interval of 7.5 years, with 2 patients developing bilateral and malignant PT. The series highlights a rare SN in childhood cancer survivors, underscoring the importance of regular long-term follow-up.

Metastatic epithelioid trophoblastic tumor in retroperitoneal nodes in a case of regressed germ cell tumor of testis: An extremely rare occurrence.

Epithelioid trophoblastic tumor is an extremely rare tumor which occurs in women of the reproductive age group following a previous gestation. Its occurrence in male patients is remarkably rare, with only six cases reported in the English literature. Herein, we discuss the unusual occurrence of this tumor in a 31-years-old male patient as a component of non-seminomatous germ cell tumor. It presented as retroperitoneal metastasis with associated testicular microlithiasis (regressed germ cell tumor).

Gastrointestinal stromal tumor presenting with lower urinary tract symptoms - A series of five cases with unusual clinical presentation.

Spindle cell tumors of the prostate are very uncommon and the majority involve the prostate secondarily from adjacent organs. Gastrointestinal stromal tumors (GISTs) are specific C-kit (CD 117) expressing mesenchymal tumors occurring in the gastrointestinal tract, commonly in the stomach and intestine; however, it is seldom seen involving the prostate. Although primary prostatic GISTs have been described, majority of them are secondary involvement from rectal GIST. The patient usually presents with urinary tract symptoms or prostate enlargement simulating a prostatic neoplasm. GIST as a differential diagnosis for prostatic mass is never thought of. We present a series of five cases of GIST arising from/involving the prostate mimicking a primary prostatic malignancy and the challenges associated with them for diagnosis and treatment.

Eosinophilic solid cystic renal cell carcinoma: A series of 3 cases elucidating the spectrum of morphological and clinical features of an emerging new entity.

Eosinophilic solid cystic renal cell carcinoma (ESC-RCC) is a recently described entity, which demonstrates distinct clinical, pathological and molecular features. We present a series of three cases, the first to be reported from the Indian subcontinent. All three patients were over 50 years of age; and presented with a large kidney mass. One patient had a locally advanced disease while the other two presented with metastases. Microscopic examination revealed a tumor displaying solid-cystic and/or papillary areas composed of clear as well as eosinophilic cells in all three cases. On immunohistochemistry, all the three cases showed a unique CK20+/α-methyl-acyl-CoA-racemase + immunophenotype. Melan-A was focally positive in Case 2. Cytokeratin 7 was focally but strongly positive in Case 3. The two patients with metastatic disease were diagnosed on core biopsies and were advised oral tyrosine kinase inhibitor therapy. The third patient underwent upfront radical nephrectomy. Due to its peculiar morphology and immunoprofile, the diagnosis of ESC-RCC can be confidently made even on a core biopsy. Most cases reported till date had an indolent course. The metastatic presentation in two of our patients emphasizes the need to gather further evidence to ascertain the biological behavior of this emerging entity.

Application and comparison of Fuhrman nuclear grading system with the novel tumor grading system for chromophobe renal cell carcinoma and its correlation with disease-specific events.

INTRODUCTION: The grading system of chromophobe renal cell carcinoma (ChRCC) is not well established. In this study, we aimed to compare the application of Fuhrman nuclear grade (FNG) with the novel chromophobe tumor grade (CTG). We also evaluated the correlation of these two grading systems with the clinical outcome. MATERIALS AND METHODS: Consecutive cases of ChRCC diagnosed on nephrectomy during 2005-2014 were identified. The clinical details of the patients were retrieved. Histopathology slides were reviewed and the nuclear grading was assigned using standard FNG and the CTG system. The CTG and FNG gradings were correlated with clinical outcome. RESULTS: A total of 80 cases were retrieved. Distribution of FNG was as follows: FNG-1, 1 (1.3%); FNG-2, 23 (28.3%); FNG-3, 44 (55.0%); and FNG-4, 12 (15%). CTG distribution was as follows: CTG-1, 48 (60.0%); CTG-2, 20 (25.0%); and CTG-3 12 (15.0%). Follow-up data was available in 46 cases; the median follow-up was 23.9 months (range 1-96.4 months). The median time to recurrence/metastasis was 17.2 months (range 3.2-31.2 months). Mean disease-free survival (DFS) was 68.5 months. Both CTG (P < 0.001) and FNG (P = 0.001) correlated with DFS; however, only CTG retained this significance when only the nonsarcomatous cases were analyzed. On receiver operating characteristics curve analysis, CTG had higher predictive accuracy for DFS for the entire group, while FNG lost the statistical significance when the nonsarcomatous cases were analyzed. CTG (P = 0.001) but not FNG (P = 0.106) correlated with the disease-specific adverse events in non-sarcomatous cases. CONCLUSIONS: It is possible to apply CTG in ChRCC. It is a better predictor of DFS and disease-specific adverse events. CTG is more appropriate and applicable than the FNG in grading ChRCC.

Triple Negative Breast Cancer: Expression of Folate Receptor Alpha in Indian population.

Folate Receptor Alpha (FRA) is a membrane protein expressed on the apical surface of epithelial cells. Its expression in increased in certain tumors, where it can serve as a target for therapy. Triple Negative Breast Carcinoma (TNBC) are a heterogeneous group of tumors, with limited therapy options and poor prognosis. We aimed to study the expression of FRA in TNBC. Tissue microarrays were prepared from archived paraffin blocks of 300 TNBC resection specimens. Staining for FRA immunohistochemistry was carried out using the clone 26B3.F2. Clinical and pathologic details of the patients were obtained from the electronic medical records. Chi square test was performed for correlation of clinicopathological features with FRA expression. Kaplan Meir and Cox Regression analysis were carried out to study the Disease Free Survival (DFS) and Overall Survival (OS). FRA showed positivity in 43% (129/300) of TNBCs in our study. In univariate analysis, TNBC expressing FRA had a significantly better OS compared to FRA negative tumors (p - 0.035). Also, FRA positive tumors showed a trend towards longer DFS, though this was not statistically significant. In multivariate analysis however, FRA expression did not emerge as a significant factor. To conclude, TNBCs in our study showed FRA expression and though this did not emerge as an important prognostic factor, it can represent a therapeutic target for future clinical trials.

Evidence for the association of Epstein-Barr Virus in breast cancer in Indian patients using in-situ hybridization technique.

Epstein-Barr Virus (EBV) is etiologically linked to Burkitt lymphoma (BL), nasopharyngeal carcinoma, post-transplant lymphomas, Hodgkin disease, and possibly other tumors. However, the association of oncogenic EBV with breast carcinoma (BC) is still controversial and a matter of debate. We aimed to study the presence of EBV genome in BC cases in Indian patients and its association with the clinicopathological features. The formalin fixed paraffin embedded tissues from 83 women with primary invasive BC were studied for the presence of EBV by in-situ hybridization (ISH) technique for Epstein-Barr Virus Encoded RNA (EBER) with appropriate controls. Correlation of EBER-ISH positivity with clinicopathological features was performed using Fisher exact test and P<.05 was considered as significant. Eighty-three BC cases were comprised of 47 (56.5%) triple negative breast cancers (TNBC), 17 (20.5%) hormone positive and 19 (22.9%) HER2 positive cases. Of 83 cases, 25 cases (30.1%) were positive for EBER-ISH test. The positivity was restricted to the tumor cells and not seen in the surrounding breast lobules. EBER-ISH positivity was statistically associated with larger tumor size (52.6% in >5 cm tumors vs 19.3% in ≤5 cm; P=.014) and with TNBCs (21/47 [44.7%] in TNBCs vs 4/36 [11.1%] in non-TNBCs; P=.001). A possible causal association of EBV in BC cases in Indian patients is suggested by high frequency of EBER-ISH positivity noted in our study. This might have therapeutic significance because of the possible role of EBV specific cytotoxic T cells in targeting EBV associated tumor cells and can be considered as a potential targeted therapy. To the best of our knowledge, this is the first study from India to address this issue using EBER-ISH technique.

Histological spectrum of oligodendroglial tumors: Only a subset shows 1p/19q codeletion.

BACKGROUND: Canonical oligodendroglial tumors (ODGs) are characterized genetically by chromosomes 1p/19q codeletion. AIMS: This study was essentially aimed at the detection of frequency of 1p/19q codeletion in the different histological spectrum of ODG tumors in a large cohort of Indian patients. MATERIALS AND METHODS: All the ODG tumors evaluated for 1p/19q by fluorescence in-situ hybridization (FISH) during 2009-2015 were correlated with histology, immunohistochemical expression for p53 protein and clinical features. RESULTS: A total of 676 cases included both pediatric (n = 18) and adult (n = 658) patients. Histologically, 346 pure ODGs [oligodendroglioma (OD) and anaplastic oligodendroglioma (AOD)] and 330 mixed ODGs [oligoastrocytomas (OA), anaplastic oligoastrocytomas (AOA) and glioblastoma with oligodendroglioma component (GBM-O)] were included. 1p/19q co-deletion was noted in 69% (60/87), 55.9% (145/259), 18.2% (18/99), 10.5% (18/172), and in 5.1% (3/59) cases of OD, AOD, OA, AOA, and GBM-O, respectively. In the pediatric age-group, 1p/19q codeletion was seen in 25% (2/8) of pure ODGs and in 10% (1/10) of mixed ODGs. In adults, it was observed in 60% (203/338) cases of pure ODGs and in 11.9% (38/320) cases of mixed ODGs. In adults, pure ODG histology (P = 0.00), frontal location (P = 0.004), calcification [in pure ODGs] (P = 0.03), and lack of p53 protein overexpression (P = 0.00) showed significant statistical correlation with 1p/19q codeletion. CONCLUSIONS: This study is unique in being one of the largest on ODGs for 1p/19q co-deletion including both pediatric and adult age groups of Indian patients. The results showed co-deletion in 60% of adult ODGs and 25% of pediatric pure ODGs. This reemphasizes the occurrence of 1p/19q codeletion, even though rare, in the pediatric age group.

Lymphoepithelioma-like carcinoma of breast-evaluation for Epstein-Barr virus-encoded RNA, human papillomavirus, and markers of basal cell differentiation.

This is a largest series of 5 cases of lymphoepithelioma-like carcinoma (LEC) of the breast attempting to look at the expression of basal cytokeratins (CKs), human papillomavirus, and Epstein-Barr virus-encoded RNAs in these tumors. Five cases were selected after stringent evaluation of all breast carcinomas showing dense lymphoid infiltration. Histologically, all these tumors showed the typical histology except 1 tumor that showed an unusual granulomatous response. All tumors were negative for estrogen and progesterone receptors and HER2 (triple negative). Three tumors expressed CK5/6 and high-molecular-weight CK, whereas only the case with nodal metastasis expressed CK14. Analysis for in situ hybridization for Epstein-Barr virus-encoded RNAs and human papillomavirus DNA on paraffin-processed tissues was negative in all tumors. All of these patients received adjuvant therapy. One patient with tumor expressing basal marker, CK5/6, had contralateral breast malignancy after a duration of 53 months of treatment completion. The rest were disease free with the follow-up period in the range of 6 to 105 months. The lymphoepithelioma-like carcinoma of breast expressed basal CK profile that is more CK5/6 positive than CK14. Analysis of basal markers within these tumors may help in refining the definition of these tumors and in classifying them into prognostically relevant groups.

Epidermal growth factor receptor (EGFR) gene amplification in high-grade gliomas: Western Indian tertiary cancer center experience.

BACKGROUND: EGFR gene amplification is the hallmark of primary glioblastomas; however, its frequency in patients of Indian origin remains sparsely investigated. AIMS: The aim of this study was to explore the frequency of EGFR amplification in high grade gliomas (HGGs) in Indian patients and to study its correlation with p53 protein overexpression. METHODS AND MATERIALS: 324 cases of HGGs, where EGFR gene amplification was evaluated by fluorescence in-situ hybridization formed the study group. Ratio of >2 was considered as EGFR gene amplification. Immunohistochemically, p53 overexpression was evaluated and graded as positive for strong intensity staining in more than 50% of tumour cells. RESULTS: 249 patients were male and 75 female (M: F-3.3:1); their age range was 8-91 years [paediatric glioblastoma (pGBM; 8-18yrs; n = 24)], adult HGGs [>18yrs; n = 300]}. 258 patients were having a GBM [including 31 with a GBM with oligodendroglioma component (GBM-O)], 31 with a gliosarcoma, 13 with an anaplastic astrocytoma (AA), 12 with an anaplastic oligodendroglioma (AO), and 10 with an anaplastic oligoastrocytoma (AOA). 79/233 cases (34%) with an adult GBM, (including 10/31 with a GBM-O [32.2%]), 1/31 (3.2%) with a GS and 1/10 (10%) with an AOA showed EGFR gene amplification. None of the pGBMs (n = 24) showed amplification. Amplification was seen in 19/81 (23.4%) of diffuse p53 protein positive cases and 53/143 (37%) of cases with focal or negative p53 protein expression. CONCLUSIONS: 34% of our adult GBM patients showed EGFR gene amplification. The amplification was uncommonly associated with a strong diffuse p53 protein expression.

Gross Evaluation of Breast Carcinomas Post-Neoadjuvant Chemotherapy Without Radio-opaque Clip Insertion.

CONTEXT.­: Gross evaluation of post-neoadjuvant chemotherapy breast carcinoma is challenging when the primary tumor is not localized before therapy with a radio-opaque wire/clip, a situation common in resource-constrained settings. OBJECTIVE.­: To compare 2 grossing approaches in post-neoadjuvant chemotherapy breast carcinoma specimens to evaluate the sampling adequacy. DESIGN.­: Fifty breast carcinoma specimens were grossed in a 2-step manner. Tumor bed was identified using clinico-radiologic and gross correlation and 1 slice was selected as most representative (sample I). Subsequently, the entire tumor bed was submitted in grids of multiple slices (sample II). Agreement between methods was assessed using κ values. RESULTS.­: Sample I prepared an average of 8 blocks per case while sample II prepared 26 blocks. Pathologic complete response (pCR) by both methods was calculated. Sample I documented 23 cases with pCR of which 21 were confirmed by sample II. The 2 cases missed by sample I had less than 5% residual tumor (residual cancer burden class I). Both cases were human epidermal growth factor receptor 2 (HER2)-positive and residual tumor was seen in the slices adjacent to the selected slice. The concordance between the 2 methods was 94% with κ value of 0.915 for sample I, indicating excellent correlation with sample II. CONCLUSIONS.­: The average cost of sample I was 33% of that of sample II and helped calculate the residual cancer burden with similar accuracy. However, in HER2-positive cases, pCR may be overestimated. Hence, we recommend sampling slices adjacent to the selected tumor slice. Further study using this method is essential due to its limited sample size and single-center design before considering implementation in the general population.

Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer.

CONTEXT.­: Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). OBJECTIVE.­: To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. DESIGN.­: D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. RESULTS.­: Concordance of 98.65% and a Cohen κ value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and κ values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (κ values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). CONCLUSIONS.­: We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status.

External Quality Assurance Helps Improve Infrastructure for Testing Breast Biomarkers Across a Lower- and Middle-Income Country: Our Experience With Breast Biomarker Testing in the National Cancer Grid External Quality Assurance System in India.

CONTEXT.­: Biomarkers in breast cancer need strict monitoring given their role in patient management. OBJECTIVE.­: To study the impact that regular participation in the National Cancer Grid (NCG) external quality assurance (EQA) system has on concordance rates for biomarkers in breast carcinoma. DESIGN.­: Tissue microarrays (TMAs) containing breast carcinomas were circulated to participating laboratories that performed immunohistochemistry for breast biomarkers. The returned TMAs were then assessed for test concordance. RESULTS.­: A total of 105 laboratories participated in the estrogen receptor (ER) and progesterone receptor (PR) EQA system cycles, and 99 centers participated in the human epidermal growth factor 2 (HER2) EQA system. In the ER EQA in the first cycle only 1 laboratory had a 100% concordance rate, which improved to 59 of 77 (76.6%) and 85 of 97 (87.6%) in the fourth and fifth cycles, respectively. In the PR EQA the 100% pass rate jumped from zero to 52 of 76 (68.4%) in the fourth cycle and 86 of 97 (88.6%) in the last cycle. For HER2 EQA, the 100% pass rates were seen in 7 of 23 laboratories (30.4%) in the first cycle, 49 of 78 laboratories (62.8%) in the fourth cycle, and 48 of 94 laboratories (51.1%) in fifth cycle of EQA. Centers that participated in the NCG EQA system for a longer period often changed testing methodology, with consequent improvement in their laboratory concordance rates. An increasing trend for the use of automated platforms and of the US Food and Drug Administration-approved antibody for HER2 testing was observed. CONCLUSIONS.­: Our experience demonstrates that laboratory performance improves with participation in an EQA system even in less perfect settings, and this drives the placement of more proficient practices across the country.

Surgical Tumor Resection Deregulates Hallmarks of Cancer in Resected Tissue and the Surrounding Microenvironment.

Surgery exposes tumor tissue to severe hypoxia and mechanical stress leading to rapid gene expression changes in the tumor and its microenvironment, which remain poorly characterized. We biopsied tumor and adjacent normal tissues from patients with breast (n = 81) and head/neck squamous cancers (HNSC; n = 10) at the beginning (A), during (B), and end of surgery (C). Tumor/normal RNA from 46/81 patients with breast cancer was subjected to mRNA-Seq using Illumina short-read technology, and from nine patients with HNSC to whole-transcriptome microarray with Illumina BeadArray. Pathways and genes involved in 7 of 10 known cancer hallmarks, namely, tumor-promoting inflammation (TNF-A, NFK-B, IL18 pathways), activation of invasion and migration (various extracellular matrix-related pathways, cell migration), sustained proliferative signaling (K-Ras Signaling), evasion of growth suppressors (P53 signaling, regulation of cell death), deregulating cellular energetics (response to lipid, secreted factors, and adipogenesis), inducing angiogenesis (hypoxia signaling, myogenesis), and avoiding immune destruction (CTLA4 and PDL1) were significantly deregulated during surgical resection (time points A vs. B vs. C). These findings were validated using NanoString assays in independent pre/intra/post-operative breast cancer samples from 48 patients. In a comparison of gene expression data from biopsy (analogous to time point A) with surgical resection samples (analogous to time point C) from The Cancer Genome Atlas study, the top deregulated genes were the same as identified in our analysis, in five of the seven studied cancer types. This study suggests that surgical extirpation deregulates the hallmarks of cancer in primary tumors and adjacent normal tissue across different cancers. IMPLICATIONS: Surgery deregulates hallmarks of cancer in human tissue.

Tata Memorial Centre Evidence Based Management of Breast cancer.

ABSTRACT: The incidence of breast cancer is increasing rapidly in urban India due to the changing lifestyle and exposure to risk factors. Diagnosis at an advanced stage and in younger women are the most concerning issues of breast cancer in India. Lack of awareness and social taboos related to cancer diagnosis make women feel hesitant to seek timely medical advice. As almost half of women develop breast cancer at an age younger than 50 years, breast cancer diagnosis poses a huge financial burden on the household and impacts the entire family. Moreover, inaccessibility, unaffordability, and high out-of-pocket expenditure make this situation grimmer. Women find it difficult to get quality cancer care closer to their homes and end up traveling long distances for seeking treatment. Significant differences in the cancer epidemiology compared to the west make the adoption of western breast cancer management guidelines challenging for Indian women. In this article, we intend to provide a comprehensive review of the management of breast cancer from diagnosis to treatment for both early and advanced stages from the perspective of low-middle-income countries. Starting with a brief introduction to epidemiology and guidelines for diagnostic modalities (imaging and pathology), treatment has been discussed for early breast cancer (EBC), locally advanced, and MBC. In-depth information on loco-regional and systemic therapy has been provided focusing on standard treatment protocols as well as scenarios where treatment can be de-escalated or escalated.

Acceptance of emerging renal oncocytic neoplasms: a survey of urologic pathologists.

Oncocytic renal neoplasms are a major source of diagnostic challenge in genitourinary pathology; however, they are typically nonaggressive in general, raising the question of whether distinguishing different subtypes, including emerging entities, is necessary. Emerging entities recently described include eosinophilic solid and cystic renal cell carcinoma (ESC RCC), low-grade oncocytic tumor (LOT), eosinophilic vacuolated tumor (EVT), and papillary renal neoplasm with reverse polarity (PRNRP). A survey was shared among 65 urologic pathologists using SurveyMonkey.com (Survey Monkey, Santa Clara, CA, USA). De-identified and anonymized respondent data were analyzed. Sixty-three participants completed the survey and contributed to the study. Participants were from Asia (n = 21; 35%), North America (n = 31; 52%), Europe (n = 6; 10%), and Australia (n = 2; 3%). Half encounter oncocytic renal neoplasms that are difficult to classify monthly or more frequently. Most (70%) indicated that there is enough evidence to consider ESC RCC as a distinct entity now, whereas there was less certainty for LOT (27%), EVT (29%), and PRNRP (37%). However, when combining the responses for sufficient evidence currently and likely in the future, LOT and EVT yielded > 70% and > 60% for PRNRP. Most (60%) would not render an outright diagnosis of oncocytoma on needle core biopsy. There was a dichotomy in the routine use of immunohistochemistry (IHC) in the evaluation of oncocytoma (yes = 52%; no = 48%). The most utilized IHC markers included keratin 7 and 20, KIT, AMACR, PAX8, CA9, melan A, succinate dehydrogenase (SDH)B, and fumarate hydratase (FH). Genetic techniques used included TSC1/TSC2/MTOR (67%) or TFE3 (74%) genes and pathways; however, the majority reported using these very rarely. Only 40% have encountered low-grade oncocytic renal neoplasms that are deficient for FH. Increasing experience with the spectrum of oncocytic renal neoplasms will likely yield further insights into the most appropriate work-up, classification, and clinical management for these entities.