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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.
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Accurate diagnosis of neuroblastoma may be challenging, especially with limited or inadequate specimen and at the metastatic sites due to overlapping imaging, histopathologic, and immunohistochemical (immunohistochemistry [IHC]; infidelity among various lineage-associated transcription factors eg FLI1, transducin-like enhancer 1, etc) features. GATA3 and ISL1 have recently been described as markers of neuroblastic differentiation. This study aims at determining the diagnostic utility of GATA3 and ISL1 in differentiating neuroblastoma from other pediatric malignant small round blue cell tumors.We evaluated GATA3 and ISL1 expression in 74 pediatric small round blue cell tumors that included 23 NMYC-amplified neuroblastomas, 11 EWSR1-rearranged round cell sarcomas, 7 SYT::SSX1-rearranged synovial sarcomas, 5 embryonal rhabdomyosarcomas, 10 Wilms tumors (nephroblastomas), 7 lymphoblastic lymphoma, 7 medulloblastoma, and 4 desmoplastic small round cell tumor.All 23 neuroblastomas (moderate to strong staining in >50% of the tumor cells), 5â T-lymphoblastic lymphomas (moderate to strong staining in 40%-90% of the tumor cells), and 2 desmoplastic small round cell tumors (weak to moderate staining in 20%-30% of the tumor cells) expressed GATA3, while other tumors were negative. ISL1 immunoreactivity was observed in 22 (96%) neuroblastomas (strong staining in in >50% of the tumor cells, n = 17; moderate to strong staining in 26%-50% of the tumor cells, n = 5), 3 embryonal rhabdomyosarcoma (moderate to strong staining in 30%-85% of the tumor cells), 1 synovial sarcoma (weak staining in 20% of the tumor cells), and 7 medulloblastoma (strong staining in 60%-90% of the tumor cells). Other tumors were negative. Overall, GATA3 showed 86% specificity, 100% sensitivity, and 90% accuracy for neuroblastoma, with a positive predictive value (PPV) and negative predictive value (NPV) of 77% and 100%, respectively. ISLI showed 72% specificity, 96% sensitivity, and 81% accuracy for neuroblastoma, with a PPV and NPV of 67% and 97%, respectively. After the exclusion of T-lymphoblastic lymphoma and desmoplastic small round cell tumors, GATA3 had 100% specificity, sensitivity, accuracy, and PPV and NPV for neuroblastoma. Similarly, in pediatric small round blue cell tumors, ISL1 had 100% specificity, sensitivity, accuracy, PPV, and NPV for neuroblastoma, after embryonal rhabdomyosarcoma, synovial sarcoma, and medulloblastoma were excluded. CONCLUSIONS: GATA3 and ISL1 may be valuable in the diagnostic work-up of neuroblastoma and may reliably be used to support the neuroblastic lineage of pediatric small round blue cell tumors. Furthermore, dual positivity helps in challenging scenarios, when there is equivocal imaging, overlapping IHC features, limited specimen, and the lack of facility for a molecular work up.
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Neoplasias Cerebelares , Neoplasias Renais , Meduloblastoma , Neuroblastoma , Leucemia-Linfoma Linfoblástico de Células Precursoras , Rabdomiossarcoma Embrionário , Sarcoma Sinovial , Tumor de Wilms , Humanos , Criança , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/genética , Neuroblastoma/diagnóstico , Tumor de Wilms/diagnóstico , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Biomarcadores Tumorais , Diagnóstico Diferencial , Fator de Transcrição GATA3RESUMO
Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion. Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor.
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Neurofibrossarcoma , Rabdomiossarcoma , Adulto , Criança , Adolescente , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Imuno-Histoquímica , Esclerose/patologia , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/patologia , Músculo Esquelético/patologia , Biomarcadores TumoraisRESUMO
OBJECTIVES: Penile squamous cell carcinomas (PCs) are rare malignancies with a dismal prognosis in a metastatic setting; therefore, novel immunotherapeutic modalities are an unmet need. One such modality is the immune checkpoint molecule programmed cell death ligand 1 (PD-L1). We sought to analyze PD-L1 expression and its correlation with various clinicopathologic parameters in a contemporary cohort of 134 patients with PC. METHODS: A cohort of 134 patients with PC was studied for PD-L1 immunohistochemistry. The PD-L1 expression was evaluated using a combined proportion score with a cutoff of 1 or higher to define positivity. The results were correlated with various clinicopathologic parameters. RESULTS: Overall, 77 (57%) patients had positive PD-L1 expression. Significantly high PD-L1 expression was observed in high-grade tumors (P = .006). We found that 37% of human papillomavirus (HPV)-associated subtypes and 73% of other histotype tumors expressed PD-L1, while 63% of HPV-associated tumors and 27% of other histotype tumors did not (odds ratio, 1.35; P = .002 when compared for HPV-associated groups vs all others). Similarly, PD-L1-positive tumors had a 3.61-times higher chance of being node positive than PD-L1-negative tumors (P = .0009). In addition, PD-L1 high-positive tumors had a 5-times higher chance of being p16ink4a negative than PD-L1 low-positive tumors (P = .004). The PD-L1-positive tumors had a lower overall survival and cancer-specific survival than PD-L1-negative tumors. CONCLUSIONS: Overall, PD-L1 expression is associated with high-grade and metastatic tumors. Lower PD-L1 expression is observed more frequently in HPV-associated (warty or basaloid) subtypes than in other, predominantly HPV-independent types. As a result, PD-L1 positivity, including higher expression, portends lower overall and cancer-specific survival. These data provide a rational for further investigating PD-L1-based immunotherapeutics in PC.
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Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Penianas , Masculino , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/metabolismo , Antígeno B7-H1/metabolismo , Ligantes , Prognóstico , Carcinoma de Células Escamosas/patologia , Neoplasias Penianas/patologia , Apoptose , Biomarcadores Tumorais/metabolismoRESUMO
Key Clinical Message: It is important to consider WDLS as a potential cause of tongue lesions and include it in the list of differential diagnoses. When performing surgical intervention, it is crucial to remove enough tissue around the lesion, and regular follow-up is necessary due to the high risk of recurrence, despite its rarity, when margins are positive. Abstract: Liposarcoma (LS) is the most common soft tissue sarcomas (STSs) that arise from embryonic mesenchymal tissue. Though these sarcomas commonly arise at retroperitoneal locations and extremities, the appearance of these tumors in the head and neck region is rare, with the tongue as a preferred site. As per WHO 2020, LS is classified into four subtypes based on morphology, namely, Well-differentiated liposarcoma (WDLS), Dedifferentiated liposarcoma (DDLS), Myxoid liposarcoma (MLS), and Pleomorphic liposarcoma (PLS). WLS is the most common variant among all. Here, we had a case of 55 years old male with the complaint of swelling in the left lateral border of the tongue with the preliminary diagnosis of pleomorphic adenoma. The patient underwent a left partial glossectomy with adequate margins. Further evaluation of the lesion revealed a clear cell tumor that was ultimately confirmed as liposarcoma on immunohistochemistry that showed tumor cells positive for S100, CDK4, and MDM2 with 2% Ki-67. Postsurgical status of the patient was evaluated by F18 FDG PET CTscan, which was normal. Currently, the patient is under regular follow-up.
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Primary renal synovial sarcoma is a rare aggressive mesenchymal neoplasm of the kidney that accounts for less than 1% of renal sarcomas. Herein, we describe the clinicopathologic and molecular findings of 14 renal synovial sarcoma patients in one of the largest case series to date and to our knowledge, the only renal synovial sarcoma series to use novel SS18-SSX IHC. Clinicopathologic, IHC, molecular, management, and follow-up data were reviewed and analyzed. Macroscopically, the tumors had either homogeneous, tan-white, and solid (n = 10), variegated and solid (n = 3), or variegated and solid-cystic (n = 1) cut surfaces. Spindle cell (n = 10), round cell (n = 3), and round to epithelioid morphologies (n = 1) were observed. SS18-SSX IHC was positive in all 14 tumors (diffuse, n = 10; multifocal, n = 2; focal, n = 2). All the tumors harbored SS18::SSX1/2 gene rearrangement. Metastases to the liver, brain, and lung (n = 1); liver and bone (n = 1); liver and diaphragm (n = 1) were identified. Adjuvant chemotherapy was administered in 11/12 patients. Follow-up was available for 10 patients (time period range: 5 to 24 months). Four patients died of disease, and six patients are alive with no recurrence or metastasis. As SS18-SSX IHC showed an excellent concordance with the FISH results, this may reliably be used in the IHC panel of spindle/round cell sarcomas of the kidney and as a molecular surrogate for renal synovial sarcoma, particularly in a resource-limited setting. Also, the tumors with focal SS18-SSX expression had lower break apart signals in the FISH assay (19% and 23% in two tumors with focal SS18-SSX IHC positivity).
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Sarcoma Sinovial , Humanos , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/genética , Proteínas de Fusão Oncogênica/genética , Pulmão/patologiaRESUMO
Background. Neuroendocrine differentiation in the prostate gland ranges from clinically insignificant neuroendocrine differentiation detected with markers in an otherwise conventional prostatic adenocarcinoma to a lethal high-grade small/large cell neuroendocrine carcinoma. The concept of neuroendocrine differentiation in prostatic adenocarcinoma has gained considerable importance due to its prognostic and therapeutic ramifications and pathologists play a pivotal role in its recognition. However, its awareness, reporting, and resource utilization practice patterns among pathologists are largely unknown. Methods. Representative examples of different spectrums of neuroendocrine differentiation along with a detailed questionnaire were shared among 39 urologic pathologists using the survey monkey software. Participants were specifically questioned about the use and awareness of the 2016 WHO classification of neuroendocrine tumors of the prostate, understanding of the clinical significance of each entity, and use of different immunohistochemical (IHC) markers. De-identified respondent data were analyzed. Results. A vast majority (90%) of the participants utilize IHC markers to confirm the diagnosis of small cell neuroendocrine carcinoma. A majority (87%) of the respondents were in agreement regarding the utilization of type of IHC markers for small cell neuroendocrine carcinoma for which 85% of the pathologists agreed that determination of the site of origin of a high-grade neuroendocrine carcinoma is not critical, as these are treated similarly. In the setting of mixed carcinomas, 62% of respondents indicated that they provide quantification and grading of the acinar component. There were varied responses regarding the prognostic implication of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and for Paneth cell-like differentiation. The classification of large cell neuroendocrine carcinoma was highly varied, with only 38% agreement in the illustrated case. Finally, despite the recommendation not to perform neuroendocrine markers in the absence of morphologic evidence of neuroendocrine differentiation, 62% would routinely utilize IHC in the work-up of a Gleason score 5 + 5 = 10 acinar adenocarcinoma and its differentiation from high-grade neuroendocrine carcinoma. Conclusion. There is a disparity in the practice utilization patterns among the urologic pathologists with regard to diagnosing high-grade neuroendocrine carcinoma and in understanding the clinical significance of focal neuroendocrine cells in an otherwise conventional acinar adenocarcinoma and Paneth cell-like neuroendocrine differentiation. There seems to have a trend towards overutilization of IHC to determine neuroendocrine differentiation in the absence of neuroendocrine features on morphology. The survey results suggest a need for further refinement and development of standardized guidelines for the classification and reporting of neuroendocrine differentiation in the prostate gland.
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Carcinoma de Células Acinares , Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Tumores Neuroendócrinos , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Patologistas , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Acinares/patologia , Carcinoma de Células Grandes/patologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that can arise at various anatomic locations. It is characterized by inv12(q13q13)-derived NAB2::STAT6 fusion, resulting in the nuclear expression of STAT6. Primary SFT of the adrenal gland is rare. We launched a multi-institutional collaboration to comprehend the overarching demographics, clinical and follow-up, macroscopic, microscopic, IHC, and FISH features of 9 patients with SFT of the adrenal gland. METHODS: We added a series of 9 patients to the collection of adrenal SFTs where the clinicopathologic parameters, including clinical presentation, imaging, histopathology, IHC, molecular profiles, and management and follow-up data, were analyzed comprehensively. A modified 4-variable risk stratification model, including age, tumor size, and necrosis, was applied. RESULTS: Our series consisted of 6 male and 3 female patients, ranging in age from 19 to 64 years (mean, 49.3 years). Abdominal pain (4) and fever with abdominal pain (1) were the presenting symptoms in 5 patients. In the remaining 4 patients, the tumors were detected by abdominal imaging for hypertension and diabetes. The size of the tumor ranged from 2 cm to 10.5 cm in maximum dimension. All tumors exhibited the morphology of a spindle cell SFT with a patternless architecture; 3 had a focal storiform arrangement. STAT6 positivity was observed in all tumors, and 7 were positive for CD34. Surgical resection was the primary modality of treatment. No adjuvant therapy was administered. Follow-up ranging from 7 months to 23 months was available for 7 patients. All were alive without disease recurrence or metastasis. Risk stratification placed 8 (88.9%) patients into a low-risk category and 1 into an intermediate-risk category. CONCLUSIONS: This series is the largest of adrenal SFTs to date. These tumors of the adrenal gland are predominantly spindle cell neoplasms with indolent behavior, with a wide age distribution and a slight male preponderance. Combining our cohort with the previously published cases, the majority of tumors fall into the low-risk category for the propensity to develop metastases. Owing to the rarity and age distribution associated with these tumors, the differential diagnosis is wide and requires a systematic approach for ruling out key differential diagnoses aided by STAT6 IHC.
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Neoplasias das Glândulas Suprarrenais , Febre Grave com Síndrome de Trombocitopenia , Tumores Fibrosos Solitários , Dor Abdominal , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT6/genética , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/patologia , Adulto JovemRESUMO
Sambit K. MohantyObjective Repressor of Silencing ( ROS1 ) gene rearrangement in the lung adenocarcinomas is one of the targetable mutually exclusive genomic alteration. Fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next-generation sequencing, and reverse transcriptase polymerase chain reaction assays are generally used to detect ROS1 gene alterations. We evaluated the correlation between ROS1 IHC and FISH analysis considering FISH as the gold standard method to determine the utility of IHC as a screening method for lung adenocarcinoma. Materials and Methods A total of 374 advanced pulmonary adenocarcinoma patients were analyzed for ROS1 IHC on Ventana Benchmark XT platform using D4D6 rabbit monoclonal antibody. FISH assay was performed in parallel in all these cases using the Vysis ROS1 Break Apart FISH probe. Statistical Analysis The sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and accuracy were evaluated. Results A total of 17 tumors were positive either by IHC or FISH analysis or both (true positive). Four tumors were positive by IHC (H-score range: 120-270), while negative on FISH analysis (false positive by IHC). One tumor was IHC negative, but positive by FISH analysis (false negative). The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, negative predictive value, and accuracy were 94.4% (confidence interval [CI]: 72.71-99.86%), 63.6% (CI: 30.79-89.07%), 2.6 (CI: 1.18-5.72), 0.09 (CI: 0.01-0.62), 80.95% (CI: 65.86-90.35%), 87.5% (CI: 49.74-98.02%), and 82.76%, respectively. Conclusion ROS1 IHC has high sensitivity at a cost of lower specificity for the detection of ROS1 gene rearrangement. All IHC positive cases should undergo a confirmatory FISH test as this testing algorithm stands as a reliable and economic tool to screen ROS1 rearrangement in lung adenocarcinomas.
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BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy. Around 25-30% patients have mismatch repair deficiency (MMRd). Lynch syndrome is caused by germline mutations in MMR genes. Lynch-associated tumours have better prognosis, however implications for prognosis and survival is less known. Microsatellite insufficiency (MSI) is associated with high neoantigen loads and number of tumor infiltrating lymphocytes, which overexpresses PD-1 and PD-L1 and are excellent candidates for PD-1-targeted immunotherapies. In this study, we aim to evaluate the utility of MMR in patients with EC and its clinico-pathological correlation. METHODS: Eighty-two cases of EC which underwent MMR evaluation over a period of five years at our centre were included. Demographics, clinical details including family history, histopathological and immunohistochemical (IHC) parameters were recorded. Tumors with loss-of at least one protein were considered MMR deficient (MMRd) and those with intact expression were MMR proficient (MMRp). RESULTS: Of 82 cases tested, 27 (33%) were MMRd. Frequencies of IHC MMR loss of expression were: MLH1/PMS2: 17 (21%), MSH6 loss only: 3 (4%), MSH2/MSH6 loss: 3 (4%), PMS2 loss: 2 (2%). In MMRd cases, most common histologic tumor type was endometrioid adenocarcinoma (70%). Loss of expression was significantly (p < 0.001) more frequent in lower uterine segment involvement and positive family history. CONCLUSIONS: MSI plays an important role in the progression of endometrial cancer. Lower uterine segment involvement and positive family history are significant predictor of MMR loss. Routine testing of MMR proteins in endometrial cancer can contribute to screening of Lynch syndrome families and make immunotherapy available as a treatment option.
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Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio , Reparo de Erro de Pareamento de DNA/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Feminino , Humanos , Imuno-Histoquímica , Instabilidade de Microssatélites , Proteína 1 Homóloga a MutL/genética , Proteína 1 Homóloga a MutL/metabolismo , Centros de Atenção TerciáriaRESUMO
BACKGROUND: Immunotherapy with checkpoint inhibitor programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies targeting the cellular immune checkpoints is the present area of interest showing promising results in patients with advanced non-small cell lung cancer (NSCLC). As there is paucity of PD-L1 expression data from the Indian perspective, we studied the correlation of clinicopathologic profile and oncogenic driver mutations in these patients. MATERIALS AND METHODS: Samples from 252 advanced NSCLCs patients were studied for PD-L1 expression through immunohistochemistry using rabbit anti-human PD-L1 monoclonal antibody (clone SP263) on Ventana BenchMark ULTRA autostainer. Simultaneously, genetic mutations were studied by next generation sequencing (for EGFR, ALK, ROS, MET, and BRAF). PD-L1 expression was analyzed for association with clinicopathologic features and various mutations. RESULTS: PD-L1 positivity was seen in 134 patients (53.2 %). It was twice more prevalent in males than females. No significant correlation was observed between PD-L1 expression with age, gender, site of testing (primary vs. metastatic tumors), smoking status, tumor laterality, stage, or histologic type; however, there was significant difference among solid and acinar types of adenocarcinoma combined together vs. other adenocarcinoma subtypes (p = 0.013), and well and moderately differentiated vs. poorly differentiated tumors (p = 0.022). When types/extent of PD-L1 positivity (≥25 %) were compared with demographics, clinical, and pathologic variables, significant differences were observed across the tumor grades (high-grade vs. low-grade) (p = 0.009) and stages (p = 0.039). The PD-L1 expression failed to demonstrate any statistical significance with oncogenic drivers. High PD-L1 expression (TPS ≥ 50) was observed in 27.6 % patients, and it was more prevalent in female patients (32.4 %), aged ≥60 years (33.8 %), smokers (27.3 %), poorly differentiated (36.8 %) and stage IV tumors (28.2 %). Exon 19 deletion was more prevalent in PD-L1 negative tumors whereas exon 21 substitution (L858R) was seen more in PD-L1 positive tumors. CONCLUSIONS: This is the largest Indian study demonstrating PD-L1 expression in NSCLC patients comparing with clinicopathologic and genomic parameters. PD-L1 expression was significantly associated with high-grade, solid, and acinar types of adenocarcinoma and advanced tumors. High PD-L1 expression was more prevalent in female patients, aged ≥60 years, smokers, and poorly differentiated and stage IV tumors (28.2 %). Exon 19 deletion was more in PD-L1 negative tumors whereas exon 21 substitution (L858R) was more in PD-L1 positive tumors. PD-L1 is a potential predictive marker stratifying patients who benefit from PD-1 pathway-targeted therapy.
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Antígeno B7-H1/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Feminino , Humanos , Índia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
OBJECTIVES: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene of non-small cell lung carcinomas (NSCLC) can be targeted by the tyrosine kinase inhibitors. A number of molecular diagnostic platforms are used to detect actionable targets in the exon(s) 18, 19, 20, and 21 of the EGFR gene. The Idylla™ system (Biocartis, Mechelen, Belgium) is a relatively novel technique and is unique in integrating both sample processing and real-time polymerase chain reaction (RT-PCR) in a single cartridge. We sought to conduct this study to compare the turnaround time (TAT) and concordance of Idylla™ system with the conventional RT-PCR and next-generation sequencing (NGS) for EGFR mutation detection. METHODS: In this retrospective analysis, 38 formalin-fixed, paraffin-embedded NSCLC tissue blocks with known NGS results by Ion Torrent™ S5 NGS platform were retested by the RT-PCR and Idylla™ platforms. RESULTS: A total of 15 of 38 (39.4 %) tumors that showed various EGFR mutations by NGS and conventional RT-PCR techniques were subjected to the Idylla™testing. These cases satisfied the specimen adequacy criteria of at least 10 % tumor cells for the testing. The mutations detected by the NGS were also detected by the Idylla™ testing. However, NGS identified additional 3 mutations in 3 cases, involving T709 V (exon 18, n = 1) and V774 M (exon 20, n = 2). The tumors with wild type EGFR on NGS did not have any actionable mutation detected by the Idylla™. Average EGFR testing TAT by Idylla™ was only 7.2 h (4-12 hours), as compared to conventional RT-PCR taking 54 h (31-79 hours) and NGS requiring 10.7 days (7.1-14 days). The actual procedure time by conventional RT-PCR was 24 h, NGS was 6.5 days, and Idylla™ was only 3 h. CONCLUSIONS: In summary, the Idylla™EGFR testing is an efficient, rapid, and fairly simple tool that can be used in the routine molecular laboratory with limited expertise and infrastructure and using the lowest amount of tissue material.
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Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Éxons , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Fluxo de TrabalhoRESUMO
Primary mucinous cystadenocarcinoma (MCA) of the breast is a rare variant of breast carcinoma known to have a favorable prognosis despite showing a basal-like phenotype. We describe a case of MCA breast in a 45-year-old female with a palpable mass in the breast. On the basis of the histopathological and immunohistochemical evaluation of a lumpectomy specimen with the absence of mass anywhere else on whole-body imaging, a diagnosis of primary MCA was rendered. Mismatch repair protein evaluation showed this tumor to be microsatellite stable. Molecular testing revealed the absence of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. To date only 27 cases of MCA breast have been reported. To the best of our knowledge, ours is the first case documenting diffuse Cytokeratin 20 (CK20) positivity, microsatellite stability, and the absence of KRAS, NRAS, and BRAF mutations in these tumors. The rarity of this tumor further evokes an interest in this case. A better understanding of the disease warrants a review of more cases with longer follow-ups.
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Mama/patologia , Cistadenocarcinoma Mucinoso/diagnóstico , Neoplasias de Mama Triplo Negativas/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Mama/cirurgia , Quimioterapia Adjuvante , Cistadenocarcinoma Mucinoso/genética , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Mucinoso/terapia , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Mutação , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
BACKGROUND AND AIMS: Sarcoidosis is a multisystem granulomatous disease of unknown etiology and cutaneous involvement is the second most frequent manifestation in systemic sarcoidosis.The aim of the present study is to evaluate the clinical and pathological spectrum of cutaneous sarcoidosis and compare the same with literature available. METHODS: The present retrospective study was conducted from January 2010-March 2015 and fifteen cases diagnosed as cutaneous sarcoidosis on biopsy were reviewed. The histological spectrum of cutaneous sarcoidosis was evaluated. RESULTS: The mean age at diagnosis was 46 years. Nine (60%) cases out of 15 were females. Most common cutaneous lesions were nodules (46.6%) followed by papules (40%). Classically, lymphocyte-poor, non-caseating epithelioid cell granulomas, was the most common histologic finding. Inclusion bodies were seen in 20% cases with occasional presence of fibrinoid necrosis (13.3%). Peri-adnexal granuloma, seen in one case, raised the possibility of tuberculoid leprosy. Foreign body was seen in one case supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. Epidermal changes including atrophy, loss of rete pegs, acanthosis, papillomatosis, hyperkeratosis, parakeratosis and basal cell vacuolation were seen in 46.6% cases. Reticulin was positive in all the cases while special stains for acid fast bacilli and fungi were negative. CONCLUSION: The clinical presentation of cutaneous sarcoidosis may be variable. Presence of naked, reticulin-rich granulomas is the most characteristic histopathological finding. Correlation of clinical history with histologic examination is essential to exclude other granulomatous diseases including leprosy, syphilis, other infectious granulomatous diseases and foreign body reaction.
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Hidradenoma Papilliferum (HP) is a rare, benign, cutaneous adnexal tumor of middle-aged females arising mainly in the apocrine sweat glands of perianal and genital region. Initially, HP was considered to be an apocrine sweat gland tumor however recent research showed that it descends from the anogenital mammary-like glands, HP can be regarded theoretically as the cutaneous complement of mammary intraductal papilloma. Nongenital HP is an infrequent manifestation, ectopic forms of this entity have been defined with bulk of them occurring on the head and neck region (60%) and 85% of cases being 1.5 cm in the greatest diameter or lesser. Average age of patients with ectopic HP is 1-2 decades older than the age range of onset in patients with anogenital HP. Here, we present a 15-year-old adolescent female with an unusually large, ectopic occurrence of nodular HP on right cheek since 2 years.
RESUMO
Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare soft tissue neoplasm most commonly occurring in the distal extremities of adult patients. It is a low-grade neoplasm with high rate of local recurrence but low rate of metastasis. We describe a case of MIFS of eyeball in an infant. An enucleation surgery was performed, and on the basis of histopathological and immunohistochemical evaluation, a diagnosis of MIFS was rendered. Till date more than 400 cases of MIFS have been reported with only a single case report of MIFS in an adult in iris. To the best of our knowledge, ours is the first case of MIFS in the eye in a child. Considering its rarity in children and especially in an infant (this seems to be the youngest patient in the literature), close follow-up is essential as the biology of these lesions cannot be predicted.
Assuntos
Neoplasias Oculares/patologia , Fibrossarcoma/patologia , Humanos , LactenteRESUMO
The clinical and pathological heterogeneity of breast cancer has instigated efforts to stratify breast cancer sub-types according to molecular profiles. These profiling efforts are now being augmented by large-scale functional screening of breast tumour cell lines, using approaches such as RNA interference. We have developed ROCK ( rock.icr.ac.uk ) to provide a unique, publicly accessible resource for the integration of breast cancer functional and molecular profiling datasets. ROCK provides a simple online interface for the navigation and cross-correlation of gene expression, aCGH and RNAi screen data. It enables the interrogation of gene lists in the context of statistically analysed functional genomic datasets, interaction networks, pathways, GO terms, mutations and drug targets. The interface also provides interactive visualisations of datasets and interaction networks. ROCK collates data from a wealth of breast cancer molecular profiling and functional screening studies into a single portal, where analysed and annotated results can be accessed at the level of a gene, sample or study. We believe that portals such as ROCK will not only afford researchers rapid access to profiling data, but also aid the integration of different data types, thus enhancing the discovery of novel targets and biomarkers for breast cancer.