Lambl's Excrescence and Management of Recurrent Cerebrovascular Accident (CVA).

Lambl's excrescence is a rare valvular finding of uncertain pathologic significance. This case describes a previously healthy 42-year-old woman experiencing a sudden onset of word-finding difficulty. MRI of the brain demonstrated acute and chronic infarcts, prompting echocardiography, which revealed Lambl's excrescence of the aortic valve.

Paratesticular Liposarcoma Presenting as an Inguinal Swelling: A Diagnostic Conundrum.

Paratesticular tumours are rare malignancies that are frequently misdiagnosed on presentation. We present a case of an elderly male with a six-month history of painless, progressively increasing left inguinal swelling. On preliminary examination and investigation, the swelling was misdiagnosed as a lymph nodal mass. Subsequently, a magnetic resonance imaging study detected a lesion that was not distinct from the spermatic cord. Biopsy testing of the said lesion was suggestive of poorly differentiated spindle cell neoplasm. The patient then underwent a high inguinal orchidectomy. Histopathological examination confirmed the diagnosis of a high-grade paratesticular dedifferentiated liposarcoma with rhabdomyoblastic differentiation. Due to the rarity of such tumours, the need for adjuvant chemotherapy and radiotherapy is debated.

Biomarker expression and impact on clinical outcomes in an international study of chemoradiation and MRI-based image-guided brachytherapy for locally advanced cervical cancer: BIOEMBRACE.

PURPOSE: BIOEMBRACE-I was designed to study the impact of biomarkers in addition to clinic-pathological factors on disease outcomes in patients treated with chemoradiation and MRI-guided brachytherapy (BT) for locally advanced cervical cancer in EMBRACE study. PATIENT AND METHODS: Between 2018-2021, eight EMBRACE-I sites contributed tumour tissue for immunohistochemistry of p16, PD-L1 and L1CAM. These biomarkers and clinicopathological factors (FIGO 2009 stage, nodal status, histology, necrosis on MRI) were analysed to predict poor response at brachytherapy (BT) (high-risk clinical target volume [HR-CTV] ≥40cc) at BT), and 5-year local control, pelvic control and disease-free survival (DFS). Interaction between p16, PD-L1, radiotherapy dose (HR-CTV D90) and disease outcomes was investigated. Univariable and multivariable analysis were performed. RESULTS: Two-hundred sixty-four patients were included. The median HR-CTV D90 was 89 (86-95) Gy. p16 positive (pos), PD-L1>1% and L1CAM ≥ 10% was noted in 86.6%, 20.1% and 17.8% respectively. P16 negative (neg) status (OR 2.0 (1.0-5.7), p=0.04), necrosis on MRI (OR 2.1 (1.1-4.3), p<0.02) independently predicted for HR-CTV≥40cc, as did FIGO stage and tumour width >5cm. PDL1>1% was associated with reduced local (82% vs. 94%, p=0.02) and pelvic control (79% vs. 89%, p=0.02). HR-CTV D90 <85Gy was associated with inferior 5-year local control in p16+ patients especially if PD-L1 was co-expressed. On multivariable analysis, PD-L1>1% was the only independent factor for 5-year local control (HR 3.3, p=0.04) and L1CAM ≥50% for pelvic control (HR 5.5 (1.3-23.3), p =0.02). CONCLUSIONS: P16 neg status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1>1% and L1CAM≥50% have an independent impact on local and pelvic control suggesting impact of biomarker expression on outcomes. Further validation is needed.

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.

An octad of fumarate hydratase-deficient uterine leiomyomas: Case series with review of literature from a single institution.

BACKGROUND: Fumarate hydratase (FH)-deficient (FH-d) leiomyomas are included in the recent World Health Organization fascicle of the female genital tumors. These are known to be associated with hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. The tumors can be diagnosed based on certain histopathological features, along with loss of immunohistochemical expression of FH immunostain in most tumors. Currently, there is no documentation on these tumors from our subcontinent. AIMS: We analyzed eight FH-d leiomyomas diagnosed at our institute. RESULTS: The most common presentation was vaginal bleeding (menorrhagia). Pelvic ultrasonogram revealed multiple fibroids in most patients except in two, who harbored a single fibroid. The size of these fibroids ranged from 3 to 19 cm. Five patients underwent myomectomies, while three underwent a total abdominal hysterectomy and bilateral salphino-ophorectomy. The most consistently observed histopathological features were hemangiopericytomatous vascular patterns, cytoplasmic globules, increased cellularity, distinct eosinophilic nucleoli, and cytological atypia (8/8, 100% tumors), followed by multinucleate giant cells and perivascular edema, seen in 62% and 50% tumors, respectively. Immunohistochemically, all tumors were positive for desmin, smooth muscle actin, and h-caldesmon and showed loss of FH immunostain, along with low Ki-67/MIB1. None of those patients had any renal or cutaneous manifestations. CONCLUSIONS: This constitutes the first such study from the Indian subcontinent and reinforces that although uterine leiomyomas constitute an integral component of the diagnosis of HLRCC syndrome, these occur in the absence of renal or cutaneous manifestations. FH-d uterine leiomyomas are more likely sporadic and could be a false alarm to raise the possibility of HLRCC with their exclusive presence.

Identification of Rare EIF3E::RSPO2 Fusion in Recurrent and Aggressive Urachal Adenocarcinoma.

INTRODUCTION: Urachal cancer (UC) is a rare genitourinary malignancy arising from the urachus, an embryonic remnant of the placental allantois. Its diagnosis remains ambiguous with late-stage cancer detection and represents a highly aggressive disease. Due to its rarity, there is no clear consensus on molecular signatures and appropriate clinical management of UC. CASE REPORT: We report a 45-year-old man with recurrent urachal adenocarcinoma (UA) treated with cystectomies, chemotherapy, and radiotherapy. The patient initially presented with hematuria and abdominal pain. Imaging revealed a nodular mass arising from the superior wall of the urinary bladder and extending to the urachus. Biopsy results suggested moderately differentiated UA with muscle layer involvement. The tumor recurred after 20 months, following which, another partial cystectomy was performed. Repeat progression was noted indicating highly aggressive disease. Targeted next-generation sequencing revealed the presence of EIF3E::RSPO2 fusion, along with BRAF and TP53 mutations, and EGFR gene amplification. This is the first case reporting the presence of this fusion in UA. Palliative medication and radiotherapy were administered to manage the disease. CONCLUSION: Current treatment modality of surgery may be effective in the early stages of recurrent UA; however, a standard chemotherapy and radiotherapy regimen is yet to be determined for advanced stages. The detection of the rare EIF3E::RSPO2 fusion warrants further studies on the significance of this variant as a possible therapeutic target for improved clinical management.

High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience.

OBJECTIVES: There is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV-positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. METHODS: Patients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000-2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. RESULTS: The majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV-positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2-99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV-negative compared to high-risk HPV-positive patients (HR 2.74, CI 1.12-8.23, P = 0.03). Moreover, among high-risk HPV-negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1-48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV-positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0-33.1). CONCLUSIONS: We demonstrate high-risk HPV-positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV-negative, and basaloid subtype in high-risk HPV-positive pSCC) may have prognostic value.

Expression of L1 Cell Adhesion Molecule, a Nephronal Principal Cell Marker, in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA's potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell-collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.

Clear cell adenocarcinoma of the cervix and its mimickers - A series of 19 cases from a tertiary care referral centre in India.

ABSTRACT: Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

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.

TFE3 rearranged epithelioid hemangioendothelioma of the lymph node: A rare primary presentation of vascular tumor.

ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor that has been described in numerous sites such as soft tissue, liver, and lungs. However, primary lymph nodal presentation of hemangioendothelioma is extremely rare. We present a 49-year-old male patient who presented with an inguinal mass but was otherwise asymptomatic. Clinical and radiological workup failed to reveal any other primary lesion. The lymph node was excised and the histomorphological examination showed an epithelioid and spindle neoplasm with chondromyxoid stroma. The diagnosis of epithelioid hemangioendothelioma was suspected based on histomorphology and immunohistochemistry, which showed diffuse positivity for CD31, CD34, and TFE3 stains. This was further confirmed by the fluorescent in-situ hybridization (FISH) technique that showed TFE3 gene rearrangement.

Can 18 F FDG PET/CT metabolic parameters be used to noninvasively differentiate between different histopathological subtypes and Fuhrman grades of renal cell cancer?

AIM: To evaluate relationship between metabolic PET metabolic parameters and size of the primary tumor, various histopathological subtypes of renal cell carcinoma (RCC) and Fuhrman grade of the tumors. MATERIAL AND METHODS: Retrospective analysis of 93 biopsy-proven RCC patients who underwent pretreatment flourine 18 flourodeoxyglucose PET/computed tomography ( 18 F FDG PET/CT) was performed. Quantitative PET parameters, size of the primary tumor, histopathological subtypes and Fuhrman grades of the tumor were extracted. We tried to assess if there was any significant difference in the metabolic patterns of various histopathological subtypes of RCCs, Fuhrman grade of the tumors and size of the primary tumor. RESULTS: A significant correlation was noted between the size of primary tumor and maximum standardized uptake value (SUV max ), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) ( P  < 0.01, P  < 0.001 and P  < 0.001, respectively). SUV max values correlated significantly with the histopathological subtype ( P  < 0.001). Further sub-analyses was also done by segregating the patients into Low grade (Fuhrman grade 1 and 2) vs. High grade (Fuhrman grade 3 and 4). SUV max , MTV and TLG were significantly different between high grade vs. low grade tumors. ROC analysis yielded cut off values for SUV max , MTV and TLG to differentiate between high grade from low grade tumors. CONCLUSION: FDG PET/CT with the use of metabolic PET parameters can differentiate between different histopathological subtypes of RCC. Incorporation of metabolic parameters into clinical practice can potentially noninvasively identify patients with low-grade vs. high-grade RCC.

Clinicopathological and Oncological Outcomes of Borderline Mucinous Tumours of Ovary: a Large Case Series.

The objective is to study the clinico-demographic profile, treatment patterns and oncological outcomes in borderline mucinous tumours of the ovary. Retrospective cohort analysis was carried out between January 2017 and December 2019 for patients with a diagnosis of borderline mucinous tumours of the ovary who were treated at our centre. Kaplan-Meier method was used for the estimation of the probability of DFS and OS. Univariate and multivariate analyses based on the Cox proportional hazard model were performed to identify factors associated with DFS and OS. A p-value ≤ 0.05 in a two-tailed test was considered statistically significant. The study population included 75 patients and the median follow-up time for the entire cohort was 24 months. The 5-year DFS for the entire cohort was 79.6% and OS was 90.5%, whereas for stage I disease, 5-year OS was 92.6% as opposed to 60% in the advanced stage. On univariate analysis, only the stage of the disease had a significant association with DFS and OS. Fertility-preserving surgeries had no impact on OS or DFS, and hence, it is suggested that fertility-sparing surgeries may be considered a viable option in young patients with mucinous ovarian tumours. Borderline mucinous tumours of the ovary have excellent survival outcomes and fertility-sparing surgeries should be done whenever feasible.

Clinical Profile and Outcomes of Carcinoma Penis Patients Receiving Systemic Therapy at an Indian tertiary care Center: A Retrospective Observational Study.

BACKGROUND: Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. METHODS: Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles. RESULTS: We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively. CONCLUSIONS: Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.

Late Urinary Toxicity and Quality of Life With Pelvic Radiation Therapy for High-Risk Prostate Cancer: Dose-Effect Relations in the POP-RT Randomized Phase 3 Trial.

PURPOSE: The POP-RT phase 3 randomized trial showed improved biochemical failure-free survival and metastasis-free survival with whole pelvic radiation therapy versus prostate-only radiation therapy for high and very high-risk prostate cancer, albeit with worse RTOG late urinary toxicity. We report updated late urinary adverse effects and bladder dose-effect relations within this trial. METHODS AND MATERIALS: Late urinary toxicity and the cumulative severity of each symptom during the follow-up period were graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Bladder dosimetry in 5-Gy increments (V5, V10, V15, V65, V68Gy) in the approved radiation therapy plans was compared with urinary symptoms and overall grade 2+ toxicity. Potential factors influencing urinary toxicity were tested using multivariable logistic regression analysis. Updated urinary quality of life (QOL) scores were compared between the trial arms. RESULTS: Complete combined data for late urinary symptoms and dosimetry was available for 193 of 224 patients. At a median follow-up of 75 months, cumulative late urinary CTCAE grade 3 toxicity was low and similar for whole pelvic radiation therapy and prostate-only radiation therapy (5.2% vs 4.1%, P = .49), and grade 2 toxicity was 31.3% versus 22.7%, respectively (P = .12). Cumulative rates of each urinary symptom were similar between both arms. Multivariable analysis with age at diagnosis, known diabetes, tumor stage, trial arm, prior transurethral resection of prostate, grade 2+ acute urinary toxicity, low bladder dose (V10Gy), and moderate bladder dose (V40Gy) did not identify any significant association with late urinary toxicity. Urinary QOL scores was similar between both the arms for all the symptoms. CONCLUSIONS: During long-term follow-up, whole pelvic radiation therapy resulted in low (∼5%) and similar grade 3 cumulative urinary toxicity as prostate-only radiation therapy. The long-term patient-reported QOL scores were similar. No causative factors affecting the late urinary toxicity were identified.

Neuroendocrine differentiation in a metachronous metastatic deposit in a case of mature growing ovarian teratoma: A rare occurrence.

ABSTRACT: Growing teratoma syndrome is a rare condition seen in non seminomatous germ cell tumor after completion of chemotherapy. Ectodermal, mesodermal and endodermal differentiation is commonly seen in mature teratoma. neuroendocrine differentiation in a metastatic deposit of mature teratoma is rarely reported. We are presenting a case of neuroendocrine differentiation in a long standing metastatic deposit of a mature teratoma.

Clinicopathological features of two ultra-rare cases of malignant perivascular epithelioid cell tumors (PEComas) involving the uterus with recent updates.

Malignant perivascular epithelioid tumors (PEComas) involving the uterus are uncommon. Herein, we present the clinicopathological features of two such cases, including their diagnostic implications with recent updates. A 62-year-old lady presented with vaginal bleeding. Ultrasonogram revealed a heterogeneous uterine mass. She underwent an endometrial biopsy and total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO), which revealed a 3.2 cm-sized proliferative tumor in the fundus. A 45-year-old lady presented with recurrent abdominal pain. She underwent cytoreductive surgery twice with adjuvant chemotherapy for multiple tumors and TAH-BSO for a uterine tumor, 2 years before. Microscopic examination of both tumors revealed markedly atypical, polygonal-shaped/epithelioid tumor cells containing eosinophilic cytoplasm and arranged in a nesting pattern with intervening thin-walled blood vessels, mitotic figures (≥ 6/10 high power fields (hpfs)), and tumor necrosis. Tumor infiltration was more than half the myometrial thickness in the first tumor and pelvic nodal metastasis. The second tumor revealed rhabdoid-like and vacuolated cells along with "spider-like" giant cells. Immunohistochemically, both the tumors were positive for HMB45 and desmin, while negative for epithelial markers. Additionally, the second tumor was positive for smooth muscle actin (SMA) and TFE3. Both patients developed tumor recurrences. In view of multiple tumor deposits, the second patient was induced with a mammalian target of rapamycin (m-TOR) inhibitor (everolimus) but unfortunately died of the disease. Malignant PEComas involving the uterus are ultra-rare, aggressive tumors. An index of suspicion, based on certain histomorphological features, supported by immunohistochemical expression of myomelanocytic markers is necessary for a correct diagnosis. Certain PEComas display TFE3 positivity. A correct diagnosis has significant implications, including an aggressive clinical course and the possibility of targeted therapy, especially in recurrences or metastasis.

Clear cell urothelial carcinoma of bladder: Case report of a rare and aggressive variant with review of literature.

Clear cell urothelial carcinoma is a rare variant of urothelial carcinoma. It's recognition and accurate diagnosis are essential in deciding appropriate treatment protocols considering the prognosis of this variant. A 57-year-old male presented with a history of hematuria and lower urinary tract symptoms for 6 months. Microscopically, the tumor was arranged in sheets and had a nested pattern. The tumor was composed of round to polygonal cells with abundant clear cytoplasm (>90% clear cell differentiation), resembling a conventional clear renal cell carcinoma. On special stain, the tumor was positive for periodic acid-Schiff (PAS) and negative for periodic acid-Schiff with diastase (PAS-D) and mucicarmine stain. The urothelial origin of clear cells was confirmed by positivity for GATA Binding protein 3(GATA3) and High Molecular Weight Cytokeratin (HMWCK) immunohistochemistry and negativity for NK3 homeobox 1(NKX3.1), Prostate specific antigen (PSA) and Paired box gene 8 (PAX8) immunohistochemistry.

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.

Para testicular cellular angiofibroma (AF)/angiomyofibroblastoma (AMF)-like tumor: A case report of a rare diagnosis in an elderly male.

Cellular angiofibroma (AF)/Angiomyofibroblastoma (AMF)-like tumor is a rare benign mesenchymal neoplasm. It is very challenging to distinguish benign versus malignant mass radiologically. It is of paramount importance to distinguish Cellular Angiofibroma (CAF) microscopically from its differential diagnoses. A 64-year-old man presented with scrotal swelling. Pathological examination showed features of cellular AF/AMF- like tumor, which shows positivity for CD34, with negativity for S-100 Protein, smooth muscle actin and desmin.