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IntroductionHuman papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC.Methods and analysisWomen aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre.Ethics and disseminationThe study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings.Trial registration numberNCT01881659.

Glioblastoma, IDH-wildtype (GBM) is a high-grade astrocytic glioma that accounts for the majority of malignant brain tumors in adults. Within this entity, epithelioid GBM represents a histological subtype characterized by a loosely cohesive aggregate of large cells with abundant cytoplasm, and vesicular nuclei that usually harbors the BRAF V600E mutation. Molecular alterations in GBMs are frequent and play an important role in the diagnosis of this entity. Among the many genetic alterations reported, NTRK fusions are rare and account for <2% of gliomas. Furthermore, NTRK2 fusions are most seen in pediatric populations. Recent approval of the TRK inhibitor larotrectinib by the Food and Drug Administration (FDA) has brought interest in the study and recognition of NTRK fusions in multiple types of tumors. Trials that assess the response to this drug in cancers carrying NTRK fusions have yielded favorable results. We discuss a rare presentation of an adult-type GBM with epithelioid morphology and a BCR::NTRK2 gene fusion. [ABSTRACT FROM AUTHOR]

We present a case report of a 54-year-old male with a metastatic testicular sex cord tumor harboring a EWSR1::ATF1 gene fusion. The tumor displayed a solid and nested architecture with sclerotic stroma and variable inflammatory infiltrate, and was positive for SF-1, inhibin, EMA, CD30, and WT1 expression. Further genetic analysis identified a EWSR1::ATF1 gene fusion. Overall findings were consistent with an "inflammatory and nested testicular sex cord tumor," a recently described testicular neoplasm characterized by EWSR1::ATF1 gene fusion and aggressive clinical behavior. Due to the aggressive nature of this entity and the limited response to current treatment options available, identification of potential biomarkers for early diagnosis and targeted therapies are critical. This case report provides important insights into the genomic landscape of testicular sex cord-stromal tumors, especially within the CTNNB1 -negative subset of patients with an aggressive clinical course, and further supports the distinction of "inflammatory and nested testicular sex cord tumor" as a separate entity from Sertoli cell tumors due to its characteristic morphological, immunohistochemical and molecular, features and clinical behavior. [ABSTRACT FROM AUTHOR]

Urinary bladder cancer is the fourth most common site of new cancer diagnosis in men after prostate, pulmonary, and colorectal cancers. It represents approximately 7% of new diagnoses and is [...], Context.--Urinary bladder flat carcinoma in situ (CIS) is a worrisome lesion, requiring aggressive surveillance and treatment. Cytokeratin 20 (CK20) and p53 are common immunohistochemical antibodies used to supplement CIS diagnosis in biopsy samples. However, existing data come primarily from unequivocally benign and malignant specimens.Objective.--To correlate these markers in specimens with borderline histology with outcomes.Design.--CK20 and p53 immunohistochemistry was analyzed for staining pattern, classified as CIS pattern (both stains yielding strong labeling of the area of concern), discordant (only 1 stain yielding CIS pattern), indeterminate (1 or both stains yielding partial or equivocal labeling), or benign (both stains yielding a benign pattern).Results.--Specimens with equivocal atypia (n = 69) from 65 patients were studied. There were 9 specimens (13%) that had a CIS staining pattern, 18 (26%) were discordant, 31 (45%) were indeterminate, and 11 (16%) were benign. Of the discordant specimens, 13 labeled for CK20 but not p53, whereas 5 showed the opposite. Most specimens (n = 47; 68%) were obtained from patients with a known history of bladder cancer, of which recurrence developed in 27, with an average interval of 37 months (range, 2-216 months). A subset (n = 22; 34%) had no prior history of bladder cancer, from which only 1 patient with CK20-positive/p53-equivocal staining later developed diagnostic carcinoma.Conclusions.--In our cohort of specimens with equivocal urothelial atypia, very few patients without a prior diagnosis of bladder cancer progressed to diagnostic cancer (1 of 22), suggesting that staining results should be interpreted with caution in de novo atypia. Patients with a known history of bladder cancer had a substantial rate of recurrence, independent of staining pattern.(Arch Pathol Lab Med. 2018;142:64-69; doi: 10.5858/arpa.2016-0411-OA)

Key Clinical Message A 24-year-old male presented with abdominal pain, fever, and palpable splenomegaly. His differential count revealed myelocytes, metamyelocytes, and nucleated red cells. A bone marrow biopsy confirmed a diagnosis of hepatosplenic gamma delta T-cell leukemia/lymphoma. We describe here our center's diagnostic and treatment approach for this rare leukemia. [ABSTRACT FROM AUTHOR]

Recurrent fusions drive the pathogenesis of many hematological malignancies. Compared to routine cytogenetic/fluorescence in situ hybridization (FISH) studies, the RNA-based next-generation sequencing (NGS) fusion assay enables the identification of both known and novel fusions. In many cases, these recurrent fusions are crucial for diagnosis and are associated with prognosis, relapse prediction, and therapeutic options. The aim of this study is to investigate the application of the RNA-based NGS fusion assay in hematological malignancies. Our study included 3101 cases with available fusion results, and a fusion event was identified in 17.6% of cases. The discordant rate between the RNA-based NGS fusion assay and cytogenetic/FISH studies was 36.3%. Further analysis of discordant cases indicated that, compared to cytogenetic/FISH studies, the RNA-based NGS fusion assay significantly improved the identification of cryptic fusion genes, such as NUP98::NSD1 , P2RY8::CRLF2 , and KMT2A fusions involving different partners. Additionally, our study identified 24 novel fusions and 16 cases with the simultaneous presence of two fusions. These additional findings from the RNA-based NGS fusion assay resulted in improved risk stratification, disease targeting and monitoring. In conclusion, our study demonstrates the feasibility and utility of an RNA-based NGS fusion assay for patients with hematological malignancies, suggesting that it may be essential for the routine clinical workup of these patients.

Erdheim-Chester disease (ECD) is a rare, xanthogranulomatous, non-Langerhans cell histiocytosis with frequent systemic involvement. Although the diagnosis is based on characteristic histological and radiological findings, its identification can be challenging because of its heterogeneous presentation. Osteosclerosis of long bones, often associated with bone pain, is the most common initial manifestation, followed by extraskeletal manifestations in approximately 50% of cases. There is no standard treatment for ECD, although recommendations have been made on the basis of small studies. A systematic approach to the diagnosis of ECD is important, because its manifestations may be life-threatening and may require specific management. We report an atypical presentation of ECD, with early cardiac, renal, and central nervous system involvement, and only late skeletal manifestations., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.