Targeted RNA sequencing in the routine clinical detection of fusion genes in salivary gland tumors.

Salivary gland tumors represent a diverse group of neoplasms that occasionally pose a diagnostic challenge for pathologists, particularly with limited sampling. Gene fusions, which may reflect genetic drivers, are increasingly recognized in a subset of these neoplasms, and can be leveraged for diagnostic purposes. We performed a retrospective analysis on a cohort of 80 benign and malignant salivary gland tumors, enriched for subtypes known to harbor recurrent fusion events, to validate the diagnostic use of a targeted RNA sequencing assay to detect fusion transcripts.

Malignant Mesothelioma With Fusion in Two Adolescent Male Patients.

Malignant mesothelioma is a neoplasm of serosal surfaces, most commonly affecting the pleura. The peritoneum, pericardium, and tunica vaginalis are less frequently involved. Malignant mesothelioma with fusion in young adults was recently reported in the literature.

Pediatric fibromyxoid soft tissue tumor with PLAG1 fusion: A novel entity?

The classification of undifferentiated soft tissue tumors continues to evolve with the expanded application of molecular analysis in clinical practice. We report three cases of a unique soft tissue tumor in young children (5 months to 2 years old) displaying a purely fibromyxoid histology, with positive staining for desmin and CD34. In two cases, RNA sequencing detected a YWHAZ-PLAG1 gene fusion, while in the third case, a previously unreported EEF1A1-PLAG1 fusion was identified.

Adult-onset neuroblastoma: Report of seven cases with molecular genetic characterization.

Whereas neuroblastoma is the most common extracranial solid tumor of childhood, less than 5% of cases occur in adults. Pediatric neuroblastoma shows marked heterogeneity of histology and molecular biology. Information about this tumor in adults is limited, especially regarding molecular biology.

Clinical and Economic Value of Routine Pathological Examination of Hernia Sacs and Scheduled Clinic Follow-Ups After Inguinal Hernia and Hydrocele Repair in a Canadian Tertiary Care Children's Hospital.

Background: The clinical and economical value of routine submission of hernia sacs for pathological examination and scheduled clinic follow-ups after inguinal hernia and hydrocele repair has been questioned. Herein, we assessed the institutional variability in these routine practices.

Methods: We retrospectively reviewed patients who underwent unilateral or bilateral inguinal hernia and/or hydrocele repair, open or laparoscopically, at our institution from 2015 to 2018.

Genetic diversity in alveolar soft part sarcoma: A subset contain variant fusion genes, highlighting broader molecular kinship with other MiT family tumors.

Alveolar soft part sarcoma (ASPS) is a rare malignancy that, since its initial description, remains a neoplasm of uncertain histogenesis. The disease-defining molecular event characterizing the diagnosis of ASPS is the ASPSCR1-TFE3 fusion gene. Following identification of an index case of ASPS with a novel TFE3 fusion partner, we performed a retrospective review to determine whether this represents an isolated event.

MYCN Amplified Relapse Following Resolution of MYCN Nonamplified 4S Neuroblastoma With Placental Involvement: A Case Report and Review of the Literature.

Congenital neuroblastoma with placental involvement is exceptionally rare, but mortality is high. Detailed examination of placenta including MYCN amplification and segmental chromosomal aberrations should be performed in all suspected cases, as it is noninvasive and readily available. Maternal dissemination has not been reported.

Fusion of ALK to the melanophilin gene MLPH in pediatric Spitz nevi.

Spitzoid neoplasms typically affect young individuals and include Spitz nevus, atypical Spitz tumor, and Spitzoid melanoma. Spitz tumors can exhibit gene fusions involving the receptor tyrosine kinases NTRK1, NTRK3, ALK, ROS1, RET, or MET, or the serine-threonine kinase BRAF. Because most studies have been based on adult cases, we studied ALK fusions in Spitz nevi occurring in pediatric patients.

Inflammation, Active Fibroplasia, and End-stage Fibrosis in 172 Biliary Atresia Remnants Correlate Poorly With Age at Kasai Portoenterostomy, Visceral Heterotaxy, and Outcome.

Published histologic studies of the hilar plate or entire biliary remnant at the time of Kasai portoenterostomy (KHPE) have not provided deep insight into the pathogenesis of biliary atresia, relation to age at surgery, prognosis or the basis for successful drainage. We report detailed histologic findings in 172 centrally reviewed biliary remnants with an average of 6 sections per subject. Active lesions were classified as either necroinflammatory (rare/clustered in a few subjects) or active concentric fibroplasia with or without inflammation (common).

Hepatoblastoma in a Child With Early-onset Cirrhosis.

Hepatoblastoma is the most common hepatic malignancy of childhood with known genetic predispositions and perinatal risk factors, with rare case reports occurring in the setting of cirrhosis. This case describes a young patient with cirrhosis attributed to early-onset hereditary hemochromatosis who was diagnosed with hepatoblastoma with uncommon histologic findings, evidence of chemotherapy resistance who ultimately succumbed to her disease. It is important to consider diagnoses beyond hepatocellular carcinoma in this scenario and consider early biopsy.

Pediatric thyroid FNA biopsy: Outcomes and impact on management over 24 years at a tertiary care center.

Background: Thyroid malignancy is rare in young children, although the incidence increases sharply during adolescence. Nodular thyroid disease and thyroid cancer in children differ substantially from those in adults, because the rates of malignancy among children are roughly 5-fold higher, and local and distant metastases as well as recurrences are more common. Even with the recent introduction of pediatric guidelines, there remains a paucity of pediatric data on which to base clinical decision making.

Recurrent NTRK1 Gene Fusions Define a Novel Subset of Locally Aggressive Lipofibromatosis-like Neural Tumors.

The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia, and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation.

Recurrent BCOR Internal Tandem Duplication and YWHAE-NUTM2B Fusions in Soft Tissue Undifferentiated Round Cell Sarcoma of Infancy: Overlapping Genetic Features With Clear Cell Sarcoma of Kidney.

Soft tissue undifferentiated round cell sarcoma (URCS) occurring in infants is a heterogenous group of tumors, often lacking known genetic abnormalities. On the basis of a t(10;17;14) karyotype in a pelvic URCS of a 4-month-old boy showing similar breakpoints with clear cell sarcoma of kidney (CCSK), we have investigated the possibility of shared genetic abnormalities in CCSK and soft tissue URCS. Most CCSKs are characterized by BCOR exon 16 internal tandem duplications (ITDs), whereas a smaller subset shows YWHAE-NUTM2B/E fusions.

A screening algorithm for the efficient exclusion of biliary atresia in infants with cholestatic jaundice.

Background: Neonates with cholestasis may undergo many tests before biliary atresia (BA) or an alternative diagnosis is reached, and delayed intervention may worsen outcomes. An optimal diagnostic approach to reduce risk, cost, and delay has yet to be defined. The purpose of this study was to develop an algorithm that rapidly and accurately excludes BA for infants with cholestatic jaundice.

Current morphologic criteria perform poorly in identifying hereditary leiomyomatosis and renal cell carcinoma syndrome-associated uterine leiomyomas.

The contemporary oncologic pathology report conveys diagnostic, prognostic, predictive, and hereditary predisposition information. Each component may be premised on a morphologic feature or a biomarker. Clinical validity and reproducibility are paramount as is standardization of reporting and clinical response to ensure individualization of patient care.

Inflammatory myofibroblastic tumors harbor multiple potentially actionable kinase fusions.

Unlabelled: Inflammatory myofibroblastic tumor (IMT) is a neoplasm that typically occurs in children. The genetic landscape of this tumor is incompletely understood and therapeutic options are limited. Although 50% of IMTs harbor anaplastic lymphoma kinase (ALK) rearrangements, no therapeutic targets have been identified in ALK-negative tumors.

Histopathological and immunohistochemical features associated with clinical response to neoadjuvant gefitinib therapy in early stage non-small cell lung cancer.

To define the pathological features associated with response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC, we have evaluated tumor histopathological features and immunohistochemical markers of proliferation (Ki-67) and epithelial mesenchymal transition (EMT) in 36 resected early stage NSCLC from patients treated preoperatively with gefitinib for 28 days. Tumors studied included 7 squamous cell carcinoma, 27 adenocarcinoma (ADC), one adenosquamous carcinoma, and one large cell carcinoma. Six of the ADC harboured an EGFR tyrosine kinase domain (TKD) mutation; five were the sensitizing type.

FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma.

Aims: To develop a fluorescence in-situ hybridisation (FISH) assay for detecting p16/CDKN2A deletion on paraffin tissue sections for use as an ancillary test to distinguish reactive from malignant mesothelial proliferations.

Method: Dual-colour FISH for p16/CDKN2A and chromosome 9 (CEP-9) was performed on 11 benign mesothelial proliferations and 54 malignant pleural mesothelioma (MPM) cases to establish cut-off values for p16/CDKN2A deletion. A third MYC probe was used to verify cases showing homozygous deletion.

Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer.

Purpose: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven efficacy in advanced non-small-cell lung cancer (NSCLC). Their role in early-stage NSCLC has not been established. Our purpose was to explore the use of preoperative gefitinib in clinical stage I NSCLC to assess tumor response, toxicity, and clinical and molecular predictors of response.

Precursor lymphoblastic lymphoma reoccurring as a donor-derived neoplasm: a case report and review of the literature.

Precursor lymphoblastic lymphoma is an uncommon neoplasm. We report the case of a man who presented with precursor T lymphoblastic lymphoma and ultimately received an allogeneic bone marrow transplant from his human leukocyte antigen-identical sister. Four years later he developed recurrent disease.

Systemic Erdheim-Chester disease.

Erdheim-Chester disease is a rare xanthomatosis that may present with characteristic radiologic and histologic features. There have been conflicting reports regarding the nature of this process, including whether it represents a reactive or neoplastic lesion. We present the clinical histories, pathologic findings, and an analysis of clonality using the HUMARA assay in two patients diagnosed with Erdheim-Chester disease.