Grossing to reporting of Wilms tumor with emphasis on proper sampling in treatment-naive and postchemotherapy specimens and their clinicopathological correlation with outcome.

Context: Emphasis on grossing to reporting for the assessment of histopathological parameters predicting outcomes in Wilms tumor. Aims: To analyze various clinicopathological parameters that effect outcomes in treatment naïve and post chemotherapy Wilms tumor specimens. Settings and Design: This was a retrospective observational study. Subjects and Methods: All patients diagnosed with Wilms tumor between 2012 and 2018 at our institute will be included with their clinical findings, laboratory reports, and radiological findings. The patients will be categorized into two groups based on treatment protocol (Society of Pediatric Oncology (SIOP) or the National Wilms Tumor Study Group/Children's Oncology Group (COG) guidelines) used. Details of Grossing and reporting protocols used for the in pre treatment and post treatment specimens will be analyzed. Follow-up till December 2020 will be analyzed. Statistical Analysis Used: Chi-square and Fisher's exact tests were used for statistical analysis. Results: A total of 36 patients with the diagnosis of Wilms tumor were included in the present study. The mean age of presentation was 3.9 ± 0.7 years, and males were more common than females. Most of them presented as abdominal mass and few with isolated hematuria. Twenty-six (72%) patients were treated under SIOP protocol with preoperative neoadjuvant chemotherapy. Ten patients underwent upfront surgery as per COG protocol. In SIOP group patients, the mean tumor size was 9.3cm. Forty percent (n = 10) we mixed histological type followed by blastemal type constituting (32%, n = 8). Regressive and epithelial histological types constituted 16% (n = 4) and 12% (n = 3), respectively. In the SIOP group 72% (n = 19) had no anaplasia and 28% (n = 7) had anaplasia. Fifty seven percent (n = 15) cases were Stage I, followed by 26.9% n = 7) and 11.5% (n = 3) being Stage II and Stage III, respectively. Ten patients underwent upfront surgery as per COG protocol. The mean tumor size among this group was 8 cm ranging from 7 cm to 11 cm. Eight (80%) cases had favorable histology and two cases showed focal anaplasia. Heterologous differentiation is seen in 3 (70%). Out of the 10 cases, one case was Stage I, six were Stage 2, one was Stage III, and two were clinical Stage IV. None of the cases showed either vessel or lymph node metastasis. All the patients received adjuvant chemotherapy postsurgery and were followed up till December 2020 for (at least 3 years). Of 25 patients in the SIOP group, 18 (72%) had complete remission with no radiological evidence of residual disease. Of the 10 patients in the COG group, 6 (70%) had complete remission. Conclusions: Histopathological evaluation of Wilms tumor is a critical aspect in the management of Wilms tumor, as tumor characteristics are different in the tumors treated under SIOP and COG protocols, which will ultimately affect the prognostic risk stratification. This necessitates the knowledge of the important grossing and reporting of these tumors under the two protocols.

Grossing and reporting of radical prostatectomy specimens: An evidence-based approach.

Radical prostatectomy (RP) constitutes the primary treatment option for patients with clinically localized, biopsy-proven prostate cancer that requires local treatment with curative intent. Accurate reporting of radical prostatectomy specimens is required to guide further risk stratification and management of patients. Hence, for the handling and reporting of RP specimens, a standardized protocol should be followed. Many general pathologists may not be well-versed with the guidelines for the handling of radical prostatectomy specimens. This article discusses a detailed approach to grossing techniques, including specimen description, fixation requirements, gross cut-up, and reporting of the grade and stage of RP specimens. This will enable the pathologist to aid in multidisciplinary management.

Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas.

Context: Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. Aims and Objectives: To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. Materials and Methods: This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Results: Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Conclusion: Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Utility of GATA-3 and associated immunohistochemical markers in the differential diagnosis of poorly differentiated urothelial carcinoma.

Aims: The aims are to study the utility of GATA-3 along with panel of immunohistochemical (IHC) markers in the differential diagnosis of primary and metastatic poorly differentiated urothelial carcinoma (UC). Settings and Design: This is a prospective and retrospective observational study. Subjects and Methods: Poorly differentiated carcinomas of urinary tract and metastatic sites from January 2016 to December 2017 were subjected to a panel of four IHC markers including GATA-3, p63, Cytokeratin (CK) 7, and CK20. Additional markers such as p16, an enzyme called alpha-methylacyl-CoA racemase, CDX2, and thyroid transcription factor 1 were also done depending on the morphology and site. Statistical Analysis Used: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of GATA-3 in making the diagnosis of UC were calculated. Results: Forty-five cases were included in the study and after appropriate IHC, the diagnosis was resolved as UC in 24 cases. GATA-3 was positive in 83.33% of UC; all the four markers positive in 33.33% and all negative in 4.17% of UC. However, at least one of the four markers was present in 95.83% of UC, except in sarcomatoid UC. GATA-3 had 100% specificity in differentiating from prostate adenocarcinoma. Conclusion: GATA-3 is a useful marker in the diagnosis of UC in the primary and metastatic sites with a sensitivity of 83.33%. GATA-3 along with other IHC markers in correlation with clinical and imageological features is necessary for making specific diagnosis of poorly differentiated carcinoma.

Unusual Cause of Acute Urinary Retention in Young Male Patient: Primary Synovial Sarcoma of Prostate-A Case Report.

Introduction Primary synovial sarcoma (SS) of the prostate is the rarest variety of prostate sarcoma. The first documented and confirmed case of SS of the prostate was published by Iwasaki et al in the year 1999; since then, only a few cases of primary SS of the prostate have been published in English literature. Case Report We report a unique case of primary SS in a young patient who presented with acute urinary retention and underwent emergency suprapubic catheterization, and on evaluation was diagnosed with primary SS of the prostate. Patient was managed with radical cystoprostatectomy and resection of the anterior wall of rectum infiltrated by the tumor with bilateral pelvic lymph node dissection and adjuvant chemotherapy. Patient died after 2 months of surgery. Conclusion Primary SS of the prostate is a rare disease and important clinical entity to be included in differential diagnosis of acute urinary retention in young patients. It is associated with high local recurrence and poor prognosis, which warrants multidisciplinary approach of treatment.

Post-treatment Residual Clinicopathological Outcomes in Testicular Germ Cell Tumours.

Surgical resection is a generally accepted treatment for residual masses after chemotherapy for metastatic testicular germ cell tumour (GCT). About half the patients have necrosis in post-chemotherapy residual masses, whereas rest have viable tumour and teratoma. The likelihood of leaving behind teratoma with its subsequent complications such as growing teratoma syndrome necessitates resection outweighing its surgical complications. Ours is a retrospective observational study and aims at assessing post-chemotherapy residual masses in testicular GCTs and to predict importance of teratomatous and non-seminomatous components. A total of 62 cases of testicular GCTs resected after chemotherapy between January 2012 and June 2019 were included. Demographic, clinical, biochemical and imageological findings were noted and categorised according to WHO classification (2016). They were divided into two groups - those who underwent retroperitoneal lymph node dissection (RPLND) post-high inguinal orchidectomy (HIO) and chemotherapy (CT) as group 1 (n = 40) and those who underwent HIO and/or RPLND post-chemotherapy as group 2 (n = 22). The gross and microscopic examination was carried out to assess response to chemotherapy in terms of residual viable tumour, necrosis and teratoma. Viable tumour, necrosis and teratoma were 10%, 62.5% and 35% respectively in group 1 and in group 2, the same were 15%, 70% and 25% respectively in HIO specimen and 7%, 50% and 21% respectively in RPLND specimen. All the cases with viable tumour were proven to be yolk sac tumours (YST) based on morphology and immunohistochemistry (IHC).Twenty cases had teratoma in the post-CT residual masses out of which 11 cases had teratoma despite reduction in size. At a median follow-up of 47.85 months, 5 cases in group 1 and 2 cases in group 2 showed relapse and it was observed that group 1 had a prolonged relapse-free survival over group 2. Our study re-emphasises the importance of performing resection of residual mass post-CT irrespective of the size, imageological or biochemical evidence of tumour regression. There does not appear to be reliable predictors of post-chemotherapy histology of residual masses indicating the continued need for surgical resection in specialised centres.

The core four - A panel of immunohistochemistry markers to diagnose and subtype testicular germ cell tumors.

CONTEXT: Immunohistochemistry (IHC) to differentiate germ cell tumors. AIMS: The aim of the study is to differentiate seminomatous and nonseminomatous germ cell tumors (GCTs) with morphological overlap using a minimal and affordable panel of IHC markers. SETTINGS AND DESIGN: This is a retrospective observational study. SUBJECTS AND METHODS: All testicular GCTs (TGCT) which were diagnosed on biopsies and/or resection specimens (prechemotherapy) between January 2014 and June 2019. The demographic, clinical, and imaging findings were noted from the medical records. Hematoxylin and eosin (H and E)-stained sections were reviewed for morphology. The IHC markers constituted Octamer-binding transcription factor (OCT) 3/4, glypican 3 (GPC3), CD117, CD30, placental-like alkaline phosphatase, Sal-like protein 4, and ß-human chorionic gonadotropin (HCG). IHC markers were performed in various combinations depending on the morphology, and a panel constituting OCT 3/4, CD117, GPC3, and CD30 was performed on cases with diagnostic dilemma and morphological overlaps. STATISTICAL ANALYSIS USED: Sensitivity, specificity, positive (PPV), and negative predictive value (NPV) were calculated for suggested panel of IHC OCT 3/4, CD117, GPC3, and CD30. RESULTS: The study included 36 patients with TGCT with a mean age of 27 (15-58) years. Nonseminomatous tumors were the most common (86%). The concise panel was performed in 20/36 (56%) tumors to resolve the diagnosis. The sensitivity, specificity, PPV, and NPV for OCT3/4 were 80%, 55%, 31%, and 92% in seminomas and 65%, 100%, 100%, and 46% in embryonal carcinomas (EC), for CD117 was 89%, 82%, 73%, and 93% in seminomas and 60%, 77%, 60%, and 77% in yolk sac tumors (YST), for GPC3 was 95%, 90%, 95%, and 90% in YST, CD30 96%, 100%, 100%, and 91% in ECs, respectively. CONCLUSIONS: Designing a novel concise and affordable IHC panel constituting OCT 3/4, CD117, GPC3, and CD30 has good sensitivity and specificity in differentiating seminomas, YST, and EC, respectively. Additional markers, namely ß-HCG, can be used in identifying the choriocarcinoma component.

GATA-3 Expression in all Grades and Different Variants of Primary and Metastatic Urothelial Carcinoma.

Urothelial carcinoma has a varied and wide histological spectrum posing a diagnostic challenge in H&E examination alone. Immunohistochemical markers like GATA-3 along with other appropriate panel of IHC can be used. However, the percentage positivity and its intensity may vary in different variants and grades of primary and metastatic urothelial carcinoma. To observe the GATA-3 expression patterns in all the grades and different variants of primary and metastatic urothelial carcinomas. It is a prospective and retrospective observational study. All the clinically suspected urothelial carcinoma (UC) during January 2016 to December 2017 were included in the study. Depending on the differential diagnosis considered, immunohistochemistry (IHC) markers including CK7, CK20, p63, AMACR, CDX2, and p16 were done to differentiate UC from other primary carcinomas. The tumors confirmed as UC were analyzed further for GATA-3 expression by Chi-square test. The number of UC in the present study was 126 including 122 (bladder in 107, ureter in 7, renal pelvis in 5, and urethra in 3) primary and 4 metastatic UC (3 in lung and 1 in liver). Age of the patients ranged from 29 to 80 (mean 61.28) years with male/female ratio 4:1. GATA-3 showed positivity in 97 (79.5%) primary UC. GATA-3 was positive in all normal urothelium and non-invasive UC (100%), while it was positive in 69/94 (73.4%) invasive UC including variants. GATA-3 was positive in 35/39 LP invasive (89.74%) and 34/55 (61.81%) MP invasive UC. GATA-3 was positive in 39/40 papillary cases (97.5%) and 45/59 (76.27%) cases of non-papillary UC. GATA-3 showed strong expression in all metastatic UC (100%). GATA-3 expression was seen in 101/126 (80.15%) of UC including primary and metastatic carcinomas and hence was a useful marker in diagnosing UC. The GATA-3 positivity decreased from normal urothelium to UC; low-grade UC to high-grade UC; non-invasive to invasive UC; lamina propria invasive to muscle invasive UC; papillary to non-papillary UC.

Differentiation of renal cell tumors with morphological cocktails using a minimal panel of immunohistochemical markers.

CONTEXT: Morphological cocktails in renal cell carcinoma (RCC). AIMS: Minimal immunohistochemistry (IHC) panel to resolve the diagnosis of renal cell cacinoma (RCC) with morphological overlaps. SETTINGS AND DESIGN: RCC is the most common malignancy in kidney accounting for 90% of all kidney cancers. Clear cell RCC is the most common histological type followed by papillary RCC. However, many of the RCCs show morphological cocktails which may pose diagnostic difficulties in small biopsies and even in the resection specimens. Accurate diagnosis has both prognostic and therapeutic implications; hence, correct differentiation is necessary. SUBJECTS AND METHODS: This retrospective study includes all renal cell tumors diagnosed on core biopsies, radical and partial nephrectomies between January 2015 and September 2017 were studied. The demographic, clinical, and gross findings were noted. The cases that had morphological overlap among the subtypes were subjected to a panel of IHC markers, including CD10, CK7, alpha-methyl acyl-coenzymeA racemase (AMACR), and CD117. RESULTS: There were 128 RCC in the study period, and morphological overlap was seen in 36 (27.9%) specimens including 13 core biopsies, 16 radical, and 7 partial nephrectomies. IHC resolved 35/36 (97.2%) cases rendering a diagnosis of clear cell (11), papillary (15), chromophobe (4), and oncocytoma (5). However, in one case where the provisional diagnosis was oncocytic tumor, all IHC markers were negative rendering IHC noncontributory. CONCLUSIONS: Difficulty in diagnosis was encountered in many core biopsies, resection specimens which when subjected to IHC panel of CD10, CK7, AMACR, and CD117 helped in resolving the diagnosis of subtypes of RCC.

Diagnostic utility of immunohistochemical marker prostein for evaluation of primary and metastatic prostatic carcinomas.

CONTEXT: The diagnosis of prostatic adenocarcinoma on histopathology depends on architectural and cytomorphological features supported by immunohistochemistry (IHC). Though all the prostate markers show excellent specificity, the sensitivity and percentage positivity vary. AIMS: In this study, we aim to study the expression of prostein in normal, benign, and malignant (primary and metastatic) lesions with particular emphasis on its utility in the differential diagnosis of poorly differentiated and metastatic prostatic adenocarcinoma along with a standard panel of IHC markers. SETTINGS AND DESIGN: This was both a prospective and retrospective as well as descriptive and observational study. SUBJECTS AND METHODS: All samples from patients with clinically suspected carcinoma prostate from both primary and metastatic sites from June 2015 to May 2016 were included in the study. Samples with difficulty in diagnosis on hematoxylin and eosin staining were subjected to a panel of IHC markers along with prostein. STATISTICAL ANALYSIS USED: Receiver operating curve analysis and Chi-square test. RESULTS: Prostein showed a 100% sensitivity and specificity to identify normal prostatic epithelium, benign and premalignant lesions, and prostatic adenocarcinoma. Prostein showed a specificity of 100% in differentiating prostatic carcinoma from poorly differentiated urothelial carcinoma and in differentiating metastatic prostatic carcinoma from adenocarcinoma of nonprostatic origin. CONCLUSIONS: Prostein is a new and promising prostate-specific marker that showed slightly more sensitivity and specificity than prostate-specific antigen. Thus, adding prostein to the IHC panel will greatly improve the detection of poorly differentiated primary and metastatic lesions of the prostate.

Diagnosis of Adrenocortical Tumors by Reticulin Algorithm.

AIMS: To apply reticulin algorithm (RA) to the diagnosis of adrenocortical tumors on adrenalectomy specimens and compare its efficacy to the modified Weiss criteria or Lin-Weiss-Bisceglia (LWB) criteria for oncocytic variant. MATERIALS AND METHODS: Adrenocortical tumors (ACTs) diagnosed on resected specimens including the variants during January 2010-June 2016 were retrieved from the pathology records. The demographic and clinical data were obtained from medical records. The functional status of the tumor was noted based on clinical and biochemical evaluation. The location, size, and gross appearance of the tumor were noted. The corresponding hematoxylin and eosin-stained slides were independently assessed by two pathologists applying modified Weiss criteria and LWB criteria for the oncocytic variant as applicable. Reticulin stain was performed on representative sections in all cases. All the tumors were classified according to RA, and the diagnoses made by each system were correlated. RESULTS: There were 15 ACTs in the study period. There were two adenomas including one oncocytoma which showed Weiss score (WS) of 2 and intact reticulin framework. There were 13 adrenal cortical carcinomas including two oncocytic variants with WS ranging from 4 to 7. There was disruption of reticulin and thick, irregular reticulin fibers in all tumors, irrespective of the histology. It correlated with modified Weiss and LWB criteria. CONCLUSIONS: The RA was simple, easy to apply, and correlated well with modified Weiss criteria in the diagnosis of ACTs including the oncocytic variant.

Prostatic High-Grade Stromal Sarcoma-A Rare Encounter.

Prostatic stromal sarcoma is a rare neoplasm, and we present a case of high-grade stromal sarcoma in a 50-year-old male with initial clinical presentation of difficulty in micturition. After initial evaluation by core needle biopsy, diagnosis was established on radical cystoprostatectomy specimen based on morphology and immunohistochemistry.

Radical Prostatectomy Findings in Men on Active Surveillance: Variable Findings Dependent on Reason for Surgery and Entry Criteria.

PURPOSE: We studied adverse radical prostatectomy findings in men on an active surveillance program with different entry and exit criteria. MATERIALS AND METHODS: The study included 80 men with biopsy progression, 33 who opted out for personal reasons and 24 who initially did not meet entry criteria mainly due to increased prostate specific antigen density. RESULTS: Of men who opted out 78.8% had a higher Gleason score of 6 than men who progressed on biopsy (46.2%, p = 0.002) and men with high prostate specific antigen density (45.8%, p = 0.02). Men with high prostate specific antigen density had less organ confined disease than the group that opted out (p <0.006) and a trend compared to the biopsy progression group (p = 0.07). Mean dominant tumor volume was lower in men who opted out than in those with biopsy progression (0.56 vs 1.1 cc, p = 0.03). The incidence of insignificant cancer was higher in men who opted out (48.4%) than in those with biopsy progression (28.4%, p = 0.05) and those with high prostate specific antigen density (20.8%, p = 0.035). There was a higher incidence of anterior tumor in men with high prostate specific antigen density (55.0%) than with biopsy progression (21.3%, p = 0.009) and a trend compared to those who opted out (27.3%, p = 0.06). CONCLUSIONS: The majority of men with biopsy progression still had tumors with features of curable disease. Men who opted out without biopsy progression had even less adverse findings, which supports counseling men to stay on active surveillance while they meet followup criteria. Men with elevated prostate specific antigen density had more anterior tumors and less organ confined cancer, substantiating that the ideal patients for active surveillance are those who meet all entry criteria.