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.

A Clinicopathological Analysis of Molecular Subtypes of Breast Cancer using Immunohistochemical Surrogates: A 6-Year Institutional Experience from a Tertiary Cancer Center in North India.

Puneet Kaur SomalObjective Classification of breast cancer into different molecular subtypes has important prognostic and therapeutic implications. The immunohistochemistry surrogate classification has been advocated for this purpose. The primary objective of the present study was to assess the prevalence of the different molecular subtypes of invasive breast carcinoma and study the clinicopathological parameters in a tertiary care cancer center in rural North India. Materials and Methods All female patients diagnosed with invasive breast cancer and registered between January 1, 2015, and December 31, 2020, were included. Patients with bilateral cancer, missing information on HER2/ER/PR receptor status, absence of reflex FISH testing after an equivocal score on Her 2 IHC were excluded. The tumors were classified into different molecular subtypes based on IHC expression as follows-luminal A-like (ER- and PR-positive, Her2-negative, Ki67 < 20%), luminal B-like Her2-negative (ER-positive, Her2-negative and any one of the following Ki67% ≥ 20% or PR-negative/low, luminal B-like Her2-positive (ER- and HER2-positive, any Ki67, any PR), Her2-positive (ER- and PR-negative, Her2-positive) and TNBC (ER, PR, Her2-negative). Chi square test was used to compare the clinicopathological parameters between these subtypes. Results A total of 1,625 cases were included. Luminal B-like subtype was the most common (41.72%). The proportion of each subtype was luminal A (15.69%), luminal B Her2-negative (23.93%), luminal B Her2-positive (17.78%), Her2-positive (15.26%), TNBC (27.32%). Majority of the tumors were Grade 3 (75.81%). Nodal metastases were present in 59%. On subanalysis of the luminal type tumors without Her2 expression (luminal A-like and luminal B-like (Her2-negative), luminal A-like tumors presented significantly with a lower grade ( p < 0.001) and more frequent node-negative disease in comparison to luminal B-like (Her2-negative) tumors. In comparison to other subtypes, TNBC tumors were more frequently seen in the premenopausal age group ( p < 0.001) and presented with node-negative disease ( p < 0.001). Conclusion This is one of the largest studies that enumerates the prevalence of various molecular subtypes of breast cancer in North India. Luminal B-like tumors were the most common followed by TNBC. TNBC tumors presented more commonly in premenopausal age group and with node negative disease in comparison to other subtypes.

Deciphering the Patterns of Dual Primary Cases Registered at the Hospital-Based Cancer Registry: First Experience from Rural Cancer Center in North India.

Objectives The objective is to present the patterns of dual primary malignancies diagnosed at the Pathology Laboratory of Cancer Hospital with the support from hospital-based cancer registry (HBCR), Sangrur, Punjab, India for the years 2018 and 2019. Methods HBCR abstracts data from electronic medical records. Trained cancer registry staff abstracts cases in standard pro forma. Dual primary was coded as per the International Agency for Research on Cancer rule and was rechecked by the pathologist. Statistical Analysis Data about multiple primary was entered and documented in an Excel sheet. Time interval was calculated by subtracting the date of diagnosis for second primary and first primary. Results A total of 6,933 cases were registered, 45 cases are dual primary (26 females, 19 males) of which 64.4% are synchronous and 35.6% metachronous cases. Seventy-nine percent received cancer-directed treatment for synchronous and 87% for metachronous. The most common sites of the primary tumor were breast (33%), head and neck (22.2%), gynecological sites (11%), prostate (9%), esophagus (4%), and remaining other tumors (20.8%). Most common sites for second malignancies were gastrointestinal (GI) tract (31%), gynecological sites (18%), head and neck (16%), hematological malignancies (7%), soft tissue sarcoma (4%), breast (2%), and other sites (22%). Conclusion More than 70% of cases of primary tumors were in breast, head and neck, gynecological, and prostate. Of these, more than 60% of the second malignancy was found in the GI tract, gynecological, and head and neck sites. Around two-thirds of dual tumors are synchronous. Breast cancer cases have higher incidence of second malignancy. Regular follow-up is necessary to assess the survival of the second primary.

EphrinB2: Expression of a novel potential target in renal cell carcinoma.

Introduction: Renal cell carcinoma (RCC) is primarily managed by surgery with the use of systemic targeted therapy in a metastatic setting. Newer targeted therapeutic options are evolving; Eph-ephrin is a potential new pathway. The therapeutic potential of targeting the EphB4-EphrinB2 pathway has been demonstrated in many solid tumors; however, its expression in RCC has only been evaluated in a few studies with limited cases. We herein determine the immunohistochemical expression of EphrinB2 in RCC. Methods: A tissue microarray comprising 110 cases of different histological subtypes of RCC and 10 normal kidney tissues were stained with monoclonal anti-EphrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the EphrinB2 were examined and its expression was correlated with sex, histological subtypes, and tumor nodes metastasis (TNM) stage. Results: Twenty cases of urothelial carcinoma and two unsatisfactory conventional clear cell RCC cases were excluded, and EphrinB2 expression was interpreted in the remaining 88 tumors. EphrinB2 was expressed in 42 out of 88 tumors (47.7%) and was negative in the normal renal parenchyma. There was a statistically significant difference in the expression of EphrinB2 in males (55%) and females (32%). However, no such difference of expression was noted for the histological subtypes and the stages. Half (51%) of Stage 1 (n = 30) and Stage 2 (n = 11) tumors showed EphrinB2 positivity. Conclusions: EphrinB2 is expressed in approximately half of RCC cases. EphrinB2 expression in the early stage cancer might indicate its induction as an early event.

Aliens in the thyroid gland: The secondary lesions.

BACKGROUND: A secondary lesion in the thyroid gland is a rare clinical scenario diagnosed preoperatively during the evaluation of a neck mass, postoperatively in a thyroidectomy specimen or in autopsy studies. Even though the thyroid gland is highly vascular, secondary malignant lesions are rare accounting for 0.2% of all thyroid malignancies. Thyroid gland secondary lesions are often metachronous in presentation as they are seldom evaluated in the initial diagnostic workup of the primary lesion. Fine-needle aspiration cytology (FNAC) is a useful modality for the diagnosis of secondary thyroid lesions. MATERIALS AND METHODS: A 6-year retrospective review (2016-2021) was carried out to assess the secondary lesions in the thyroid gland. Papanicolaou and field-stained FNAC smears of secondary thyroid lesions were reviewed. Ancillary techniques were performed on the cell block for differentiating from the primary thyroid gland lesions. RESULTS: There were 383 patients in our archives. There were only 18 cases (4.7%) that presented with secondary neoplastic lesions in the thyroid gland either by direct extension, metastases or as a hematolymphoid malignancy. There were 14 (77.7%) cases that presented with non-hematolymphoid secondary lesions while 4 (22.3%) cases presented with hematolymphoid malignancies. Thyroid secondaries were predominantly seen in female patients (female: male ratio of 1.5:1). Most of the cases presented with a synchronous secondary lesion (n = 14, 77.7%) and few metachronous secondary lesions were also noted (n = 4, 22.3%). CONCLUSION: Although exceedingly rare, the detection of secondary thyroid gland lesions is important for staging and planning treatment.

Early endometrial carcinoma: Experience and outcomes.

Aim: Endometrial carcinoma (EC) data from India are very sparse. We did a retrospective analysis of our patients registered at this peripheral cancer center based in rural Punjab and studied their outcome. Materials and Methods: Ninety-eight Stage I and II EC patients with endometroid histology registered at our institute from January 2015 to April 2020 were studied for demography, histopathology, treatment received, and outcomes. FIGO 2009 staging and new European Society for Medical Oncology (ESMO) risk group classification was used. Results: Our patients had a median age of 60 years (range 32-93 years). There were 39 (39.8%), 41 (42.0%), 4 (4.1%), 12 (12.2%) patients in the low risk, intermediate risk (IR), high intermediate risk, and high risk groups, respectively, as per new ESMO risk classification. Two (2.0%) patients had incomplete information to assign them to a particular risk group. Fifty (46.7%) patients underwent complete surgical staging and 54 (50.5%) patients received adjuvant RT. With a median follow-up of 27.0 months, there were 1 locoregional and 2 distant recurrences. There were 8 deaths in total. Three-year overall survival for the entire group is 90.6%. Conclusions: The risk group determines adjuvant treatment in endometrial cancer. Patients operated at dedicated cancer center tend to have better surgical staging and thus better outcome because of better risk stratification and grouping for adjuvant therapy. IR histology was more common in our group of patients, which is variable as compared to available literature.

Challenges Encountered and Pattern-Based Analysis of Bone Marrow Biopsy in Lymphomas: An Institutional Experience.

Objective The evaluation of bone marrow (BM) status is an integral part of the initial workup of patients diagnosed with lymphoma as it plays an important role in staging and predicting prognosis in these patients. This article determines the incidence and pattern of BM involvement in lymphoma cases and distinguishes benign from malignant lymphoid aggregates in BM biopsies. Materials and Methods The study group included 121 cases of Hodgkin and non-Hodgkin lymphomas for which BM biopsies were performed, fixed in acetic acid-zinc formalin solution, decalcified using 10% formic acid, and subjected to hematoxylin and eosin and immunohistochemistry. Results The overall incidence of BM biopsy involvement in our study was 31.4% (37/118), including 34.7% (35/101) in cases of B cell lymphomas, 25% (2/8) in cases of T cell lymphomas, and no involvement in Hodgkin lymphoma. The predominant histological pattern of BM involvement was diffused (14/37; 37.8%), followed by interstitial (10/37; 27.1%). Five cases revealed benign nonparatrabecular lymphoid aggregates which could be confused with lymphomatous involvement, especially in low grade lymphomas. Conclusion A careful examination of the BM biopsies along with clinical history, peripheral blood examination, flow cytometry, and immunohistochemistry will help in arriving at the correct diagnosis.

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.

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.

Immunohistochemistry on cell blocks for diagnosis of malignancy in abdomino-pelvic lesions and ascitic fluid cytology at a rural cancer center: A paradigm shift in cancer management.

Background: Cell block preparation is routine practice in cytopathology these days because of its pivotal role in increasing diagnostic yield and ancillary studies. In the present era of personalized medicine in oncology, ancillary techniques such as immunohistochemistry (IHC) and molecular analysis are gaining more importance. Methods: A retrospective study was conducted in the Department of Pathology, over 6 months, which included 144 cases of Fine Needle Aspiration Cytology (FNAC) of abdominopelvic masses and 105 cases of ascitic fluids. Cell blocks and conventional smears were prepared simultaneously in all cases. IHC was applied on cell blocks and analyzed. Results: IHC was performed on cell blocks in 76 cases of FNA and 53 cases of ascitic fluids. Based on IHC, liver lesions (50 cases) were categorized into metastatic carcinomas with a suggested primary site (45.0%), hepatocellular carcinoma (12.2%), neuroendocrine tumors (16.3%), and malignant melanoma (2%). Using MOC-31 and WT-1, ascitic fluid samples were categorized into benign and malignant. Forty-one out of 53 cases of fluids were diagnosed as metastatic adenocarcinomas with the ovary as the most common primary site. Conclusion: A panel of IHC markers, though not specific alone when applied to cell blocks in a careful clinical and morphological context leads to a rapid and accurate diagnosis. This in turn obviates the need for biopsy in severely ill patients. An astute pathologist can provide accurate results with judicious use of IHC on cell blocks and may bring a sigh of relief for many cancer patients by averting the need for biopsy.

Feasibility of using CT radiomic signatures for predicting CD8-T cell infiltration and PD-L1 expression in renal cell carcinoma.

Objectives: To identify computed tomography (CT)-based radiomic signatures of cluster of differentiation 8 (CD8)-T cell infiltration and programmed cell death ligand 1 (PD-L1) expression levels in patients with clear-cell renal cell carcinoma (ccRCC). Methods: Seventy-eight patients with pathologically confirmed localized ccRCC, preoperative multiphase CT and tumor resection specimens were enrolled in this retrospective study. Regions of interest (ROI) of the ccRCC volume were manually segmented from the CT images and processed using a radiomics panel comprising of 1708 metrics. The extracted metrics were used as inputs to three machine learning classifiers: Random Forest, AdaBoost, and ElasticNet to create radiomic signatures for CD8-T cell infiltration and PD-L1 expression, respectively. Results: Using a cut-off of 80 lymphocytes per high power field, 59 % were classified to CD8 highly infiltrated tumors and 41 % were CD8 non highly infiltrated tumors, respectively. An ElasticNet classifier discriminated between these two groups of CD8-T cells with an AUC of 0.68 (95 % CI, 0.55-0.80). In addition, based on tumor proportion score with a cut-off of > 1 % tumor cells expressing PD-L1, 76 % were PD-L1 positive and 24 % were PD-L1 negative. An Adaboost classifier discriminated between PD-L1 positive and PD-L1 negative tumors with an AUC of 0.8 95 % CI: (0.66, 0.95). 3D radiomics metrics of graylevel co-occurrence matrix (GLCM) and graylevel run-length matrix (GLRLM) metrics drove the performance for CD8-Tcell and PD-L1 classification, respectively. Conclusions: CT-radiomic signatures can differentiate tumors with high CD8-T cell infiltration with moderate accuracy and positive PD-L1 expression with good accuracy in ccRCC.

Adequacy of Histopathology Reports Representing Oncologic Resection Specimens: An Experience of Reporting Practice in Rural India.

CONTEXT.­: The histopathology reporting practice in rural areas is largely variable. To ensure the adequacy of histopathology reports (HPRs), the College of American Pathologists (CAP) has developed cancer reporting checklists. OBJECTIVE.­: To assess the adequacy of resection specimen HPRs received from outside centers for a second opinion. Further, the adequacy of breast resection HPRs from these centers was compared with that of our center. Additionally, the reports representing endometrial carcinoma were assessed for impact on the treatment decision. DESIGN.­: This was a retrospective study conducted from June 2015 to December 2019. HPRs from outside centers and our institute were analyzed for mandatory reporting elements as per CAP 2013 checklists. RESULTS.­: A total of 730 HPRs (558 outside HPRs and 172 in-house breast HPRs) were reviewed for completeness. The outside HPRs were complete in 42 of 558 cases (7.5%). Only 11 of 143 reports (7.7%) from the academic centers were complete. Seventeen of 249 outside breast HPRs (6.8%) were complete, whereas predominant (n = 123 of 172; 71.5%) in-house breast HPRs were adequate. Most outside endometrial carcinoma reports (60.8%; n = 28 of 46) were inadequate with potential impact on the adjuvant treatment, whereas 10 of 46 reports (21.7%) were inadequate and had an actual impact on the adjuvant treatment decision. CONCLUSIONS.­: Minimal data set reporting using checklists is not yet widely operational in most rural laboratories. We call for continuous education and sensitization of the practicing pathologists, oncopathology education of the trainees, and regulatory standards for signing out an oncopathology report.

Primary angiosarcoma of the seminal vesicle.

Angiosarcomas are rare but highly aggressive malignancies originating from lymphatic or vascular endothelial cells and may arise from any site in the body. Angiosarcomas of the genitourinary tract, especially of seminal vesicle origin, are extremely rare with only five reported cases. Surgery forms the mainstay of therapy in localised disease while adjuvant therapies are still being refined. We present the case of a 40-year old gentleman who presented with lower urinary tract symptoms and, on evaluation, was found to have a localised angiosarcoma originating in right seminal vesicle and offered laparoscopic resection, adjuvant paclitaxel (12 weekly cycles) and adjuvant radiation therapy (66 gray in 30 fractions). He developed a peritoneal nodular recurrence after 6 months of radiotherapy that was successfully salvaged with excision and metronomic chemotherapy, which he is currently receiving. Localised angiosarcomas need multimodality management despite small size. Attempts should be made for surgical salvage of limited recurrences whenever feasible.

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.

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 a Portable Whole-Slide Imaging System for Frozen Section Diagnosis.

BACKGROUND: Frozen section (FS) diagnosis is one of the promising applications of digital pathology (DP). However, the implementation of an appropriate and economically viable DP solution for FS in routine practice is challenging. The objective of this study was to establish the non-inferiority of whole-slide imaging (WSI) versus optical microscopy (OM) for FS diagnosis using a low cost and portable DP system. MATERIALS AND METHODS: A validation study to investigate the technical performance and diagnostic accuracy of WSI versus OM for FS diagnosis was performed using 60 FS cases[120 slides i.e, 60 hematoxylin and eosin (H & E) and 60 toluidine blue (TOLB)]. The diagnostic concordance, inter- and intra-observer agreement for FS diagnosis by WSI versus OM were recorded. RESULTS: The first time successful scanning rate was 89.1% (107/120). Mean scanning time per slide for H and E and TOLB slide was 1:47 min (range; 0:22-3: 21 min) and 1:46 min (range; 0:21-3: 20 min), respectively. Mean storage space per slide for H and E and TOLB slide was 0.83 GB (range: 0.12-1.73 GB) and 0.71 GB (range: 0.11-1.66 GB), respectively. Considering major discrepancies, the overall diagnostic concordance for OM and WSI, when compared with the reference standard, was 95.42% and 95.83%, respectively. There was almost perfect intra as well as inter-observer agreement (k ≥ 0.8) among 4 pathologists between WSI and OM for FS diagnosis. Mean turnaround time (TAT) of 14:58 min was observed using WSI for FS diagnosis, which was within the College of American Pathologists recommended range for FS reporting. The image quality was average to best quality in most of the cases. CONCLUSION: WSI was noninferior to OM for FS diagnosis across various specimen types. This portable WSI system can be safely adopted for routine FS diagnosis and provides an economically viable alternative to high-end scanners.

Strategies to ensure efficient laboratory functioning while navigating through the COVID-19 crisis in developing countries: An early experience from a tertiary care centre in India.

BACKGROUND: The coronavirus disease 2019 (COVID 19) is a zoonotic viral infection that originated in Wuhan, China, in December 2019. It was declared a pandemic by the World Health Organization shortly thereafter. This pandemic is going to have a lasting impact on the functioning of pathology laboratories due to the frequent handling of potentially infectious samples by the laboratory personnel. To deal with this unprecedented situation, various national and international guidelines have been put forward outlining the precautions to be taken during sample processing from a potentially infectious patient. PURPOSE: Most of these guidelines are centered around laboratories that are a part of designated COVID 19 hospitals. However, proper protocols need to be in place in all laboratories, irrespective of whether they are a part of COVID 19 hospital or not as this would greatly reduce the risk of exposure of laboratory/hospital personnel. As part of a laboratory associated with a rural cancer hospital which is not a dedicated COVID 19 hospital, we aim to present our institute's experience in handling pathology specimens during the COVID 19 era. CONCLUSION: We hope this will address the concerns of small to medium sized laboratories and help them build an effective strategy required for protecting the laboratory personnel from risk of exposure and also ensure smooth and optimum functioning of the laboratory services.