Publications by authors named "Jeffrey Gagan"

Sialadenoma papilliferum is a tumor characterized by surface papillary projections and glandular/microcystic proliferation at the lesion base. Cases in which surface involvement is absent have been termed "sialadenoma papilliferum-like intraductal papillary tumor." Similar tumors that are present in the mandible have been termed "tubulopapillary hidradenoma-like tumor of the mandible.

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Astrocytomas that harbor recurrent genomic alterations in MYB or MYBL1 are a group of Pediatric-type diffuse low-grade gliomas that were newly recognized in the 2021 WHO Classification of Tumors of the Central Nervous System. These tumors are described in the WHO classification as harboring fusions in MYB or MYBL1. In this report, we examine 14 consecutive cases in which a MYB or MYBL1 alteration was identified, each with diagnostic confirmation by genome-wide DNA methylation profiling (6 Angiocentric gliomas and 8 Diffuse astrocytomas, MYB- or MYBL1-altered), for their specific genomic alterations in these genes.

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Squamous cell carcinoma (SCC) is one of the most common malignancies involving the parotid gland, but it has been recognized that the vast majority of parotid SCC represents metastases, especially from the ipsilateral facial skin. Bona fide primary SCC of the parotid is so rare that it is unclear whether it truly exists at all. We sought to molecularly characterize cases diagnosed as primary parotid gland SCC to see if they possess a unique genetic makeup.

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Xanthogranulomatous epithelial tumor (XGET) and HMGA2::NCOR2 fusion keratin-positive giant cell-rich tumor (KPGCT) are recently described morphologically overlapping rare neoplastic entities characterized by HMGA2::NCOR2 fusions, low-grade biological behavior, and a strong predilection for young females. To date, 47 cases have been reported with only four occurring in head and neck anatomic locations. In this study, we describe the clinicopathologic, immunohistochemical, and molecular findings of seven XGET/KPGCTs occurring in the head and neck region.

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Background: Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed.

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Odontogenic tumors represent a collection of entities ranging from hamartomas to destructive benign and malignant neoplasms. Occasionally, pathologists encounter gnathic lesions which clearly exhibit an odontogenic origin but do not fit within the confines of established diagnoses. Here, we describe two such odontogenic tumors, both affecting 3-year-old males.

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Translocation renal cell carcinoma (tRCC) most commonly involves an ASPSCR1-TFE3 fusion, but molecular mechanisms remain elusive and animal models are lacking. Here, we show that human ASPSCR1-TFE3 driven by Pax8-Cre (a credentialed clear cell RCC driver) disrupted nephrogenesis and glomerular development, causing neonatal death, while the clear cell RCC failed driver, Sglt2-Cre, induced aggressive tRCC (as well as alveolar soft part sarcoma) with complete penetrance and short latency. However, in both contexts, ASPSCR1-TFE3 led to characteristic morphological cellular changes, loss of epithelial markers, and an epithelial-mesenchymal transition.

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T/myeloid mixed phenotype acute leukaemia (MPAL) is a rare aggressive acute leukaemia with poorly understood pathogenesis. Herein, we report two cases of T/myeloid MPAL harbouring BCL11B-associated structural variants that activate TLX3 (TLX3::BCL11B-TLX3-activation) by genome sequencing and transcriptomic analyses. Both patients were young males with extramedullary involvement.

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Article Synopsis
  • This study highlighted the limitations of fluorescent in situ hybridization (FISH) methods in accurately diagnosing hematologic malignancies, as some signals may not represent true gene fusions due to probe design issues.
  • It compared results from traditional cytogenetic methods and FISH with next-generation sequencing (NGS) and RNA sequencing (RNASeq) in three patient cases.
  • The findings emphasized the importance of using NGS/RNASeq for a more accurate interpretation of FISH results, especially when the signals observed are atypical or unclear.
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Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated.

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B/T mixed phenotype acute leukemia (MPAL) is a rare aggressive leukemia. Three cases of B/T MPAL were identified with comprehensive immunophenotypic, cytogenetic, and molecular studies. T-lineage predominant B/T MPAL shares a genetic signature with T-ALL whereas B/T lineage co-dominant B/T MPAL lacks such a T-ALL signature All three patients were treated with lineage-matched-ALL therapy and alive at the last follow-up.

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Keratocystoma is a rare salivary gland lesion that has been reported primarily in children and young adults. Because of a scarcity of reported cases, very little is known about it, including its molecular underpinnings, biological potential, and histologic spectrum. Purported to be a benign neoplasm, keratocystoma bears a striking histologic resemblance to benign lesions like metaplastic Warthin tumor on one end of the spectrum and squamous cell carcinoma on the other end.

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Article Synopsis
  • * Certain fusion partners, like MED15, alter the tumor's appearance, causing it to resemble less harmful cystic tumors.
  • * This text discusses a specific case of MED15::TFE3 RCC in an older adult and offers insights into diagnosing similar low-grade renal tumors effectively.
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A group of gene mutations has been identified to be strongly associated with secondary acute myeloid leukemias (AML) arising from prior myeloid neoplasms. The International Consensus Classification (ICC) and proposed 5th edition of the World Health Organization (WHO) classification differ by inclusion of . A recent study suggested that having two or more secondary mutations is associated with a particularly poor prognosis.

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Article Synopsis
  • * This study involved analyzing 54 PAC cases using next-generation sequencing (NGS), focusing on the cribriform subtype to uncover gene fusions that could provide more insights into the cancer's molecular profile.
  • * The results revealed 28 cases with significant fusions, including 13 novel gene partners, showing a complex genetic makeup that suggests the need for extensive sequencing in difficult cases.
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The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes.

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Adamantinoma-like Ewing sarcoma (ALES) is a rare malignancy currently considered a variant of Ewing sarcoma with most known cases harboring EWSR1 rearrangements. Herein we present a series of 6 cases of EWSR1 -negative ALES. The tumors arose in the sinonasal tract (n=3), major salivary glands (submandibular gland=1; parotid=1), and anterior mediastinum (n=1) in patients ranging from 25 to 79 years of age.

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Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) germ cell tumor (GCT) pre-orchiectomy; however, its ability to detect occult disease is understudied. To refine the serum miR-371a-3p assay in the minimal residual disease setting we compared performance of raw (Cq) and normalized (∆Cq, RQ) values from prior assays, and validated interlaboratory concordance by aliquot swapping. Revised assay performance was determined in a cohort of 32 patients suspected of occult retroperitoneal disease.

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Article Synopsis
  • Adenocarcinoma, NOS is a complex group of salivary gland tumors that includes tumors not yet well-defined, with some cases being reclassed into new categories like secretory carcinoma and microsecretory adenocarcinoma.
  • A study identified nine cases of a new salivary gland tumor type, predominantly affecting older women, particularly arising in the sublingual gland.
  • The tumors exhibited a unique biphasic structure with specific cell characteristics and immunohistochemical profiles, but no significant genetic mutations were found, and all were surgically removed.
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While molecular testing of hematologic malignancies is now standard of care, there is variability in practice and testing capabilities between different academic laboratories, with common questions arising on how to best meet clinical expectations. A survey was sent to hematopathology subgroup members of the Genomics Organization for Academic Laboratories consortium to assess current and future practice and potentially establish a reference for peer institutions. Responses were received from 18 academic tertiary-care laboratories regarding next-generation sequencing (NGS) panel design, sequencing protocols and metrics, assay characteristics, laboratory operations, case reimbursement, and development plans.

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Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) GCT pre-orchiectomy; however, its ability to detect occult disease is understudied. To refine the serum miR-371a-3p assay in the minimal residual disease setting we compared performance of raw (Cq) and normalized (∆Cq, RQ) values from prior assays, and validated interlaboratory concordance by aliquot swapping. Revised assay performance was determined in a cohort of 32 patients suspected of occult retroperitoneal disease.

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TEMPI syndrome is a new and poorly understood disease that is currently considered a type of plasma cell neoplasm with paraneoplastic manifestations. The TEMPI acronym defines the hallmarks of the syndrome: T for telangiectasia; E for erythrocytosis with elevated erythropoietin; M, monoclonal gammopathy; P, perinephric collections; and I, intrapulmonary shunting. Due to the marked erythrocytosis as the most common presenting feature, TEMPI is often misdiagnosed as polycythemia vera.

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Striated duct adenoma (SDA) is a rare salivary gland neoplasm defined by histologic similarity to normal striated ducts. However, doubt persists about whether SDA represents a genuine entity distinct from canalicular adenoma and if a malignant counterpart exists. This study aims to evaluate the molecular underpinnings of SDA to clarify its pathogenesis and classification.

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