Publications by authors named "Michelle S Hirsch"

Article Synopsis
  • - Oncocytic renal neoplasms pose significant diagnostic challenges, yet are generally nonaggressive, prompting discussion about the necessity of differentiating emerging subtypes like eosinophilic solid and cystic renal cell carcinoma and others.
  • - A survey of 63 urologic pathologists revealed that many encounter complex oncocytic tumors frequently, with 70% agreeing that eosinophilic solid and cystic renal cell carcinoma should be recognized as a distinct category, while opinions were more divided on other types.
  • - Diagnostic approaches varied among pathologists, with 60% hesitant to diagnose oncocytoma through needle biopsies, and a near split on the routine use of immunohistochemistry; common genetic testing was
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Background: Papillary renal neoplasm with reverse polarity is a recently recognized low-grade neoplasm with a favorable prognosis. To date, its cytologic features have not been well documented.

Methods: Two patients with papillary renal neoplasm with reverse polarity sampled by fine needle aspiration and core needle biopsy are described, one of whom is under active surveillance without clinical progression and the other is alive and well 16 years after partial nephrectomy.

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Aims: Recently, SOX17 has emerged as a promising biomarker for non-mucinous Müllerian (ovarian and endometrial) carcinomas, demonstrating increased specificity in comparison to PAX8 while maintaining similar sensitivity. However, expression of SOX17 in mesonephric-like adenocarcinoma (MLA), a carcinoma of the female genital tract with uncertain, but probably Müllerian histogenesis, remains unexplored. This study aims to address this gap.

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  • Spindle cell-rich testicular sex cord-stromal tumors (TSCSTs) include types like myoid gonadal stromal tumor (MGST), adult granulosa cell tumor (AGCT), and unclassified TSCST, showing histopathologic similarities and lacking clear oncogenic drivers.
  • DNA sequencing indicates common chromosomal gains in these tumors, but further validation of these findings has not yet taken place, and the amount of chromosomal alterations varies among individual tumors.
  • This study used fluorescence in-situ hybridization (FISH) to assess chromosomal changes in 10 tumors, revealing consistent increases in specific chromosomes across various cases, while also uncovering partial disagreements between FISH analysis and previous genomic sequencing results,
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Article Synopsis
  • * The survey received an 85% response rate from 98 uropathologists, revealing strong agreement on distinguishing between luminal and basal UC types, but varied opinions on the importance of certain genetic tests like FGFR3 and TERT promoter mutations.
  • * Most uropathologists acknowledged the aggressive nature of tumors with micropapillary features and favored further evaluation and specific molecular testing for aggressive subtypes, indicating a need for improved consensus in UC classification and treatment strategies.
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Ovarian immature teratoma (IT) is a rare neoplasm comprising ∼3% of ovarian cancers, occurring primarily in young females. Management presents several challenges, including those with elevated serum alpha-fetoprotein, potential confusion regarding pathology interpretation, and paucity of data to support decision-making. MaGIC (https://magicconsortium.

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Ovarian-type (ie, Mullerian) epithelial tumors occurring in the testicular and paratesticular regions are exceptionally rare, with only a handful reported worldwide. Serous tumors are the most frequently encountered subtype among these rare tumors. The pathogenesis of these tumors within the testicular and paratesticular regions remains a subject of intrigue and debate, with various hypotheses attempting to explain their presence in the paratestis region, where most tumors occur.

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Aims: The 2022 WHO classification for kidney tumours recently downgraded clear cell tubulopapillary (also known as clear cell papillary) renal cell carcinoma (RCC) to a benign neoplasm (i.e. clear cell tubulopapillary renal cell tumour) based on the overwhelmingly banal nature of this neoplasm.

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Purpose: The 2022 World Health Organization classification of renal neoplasia expanded the spectrum of oncocytic neoplasms to encompass newly established and emerging entities; one of the latter is the low-grade oncocytic tumor (LOT). This study reports the radiologic appearance and clinical behavior of LOT.

Methods: In this IRB-approved, HIPPA-compliant retrospective study, our institution's pathology database was searched for low-grade oncocytic tumors or neoplasms.

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Introduction/background: Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer (PCa). Better biomarkers are needed to predict responses to ICIs. We sought to demonstrate that a panel-based mutational signature identifies mismatch repair (MMR) deficient (MMRd) PCa and is a biomarker of response to pembrolizumab.

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Prepubertal-type teratomas are uncommon, especially in postpubertal male patients. We document a case of a 28-year-old man with a lifelong history of bilateral testicular masses who presented with scrotal fistulas and no clinical evidence of extratesticular disease. Bilateral radical orchiectomies demonstrated large bilateral solid and cystic masses that contained grossly visible hairs.

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Article Synopsis
  • * In a study analyzing paired conventional and sarcomatoid components from 8 chRCC samples, researchers found that nearly all tumors had TP53 gene variants, with different patterns of variance between components.
  • * The results indicate that the transformation may be driven by the presence of TP53 mutations followed by whole-genome duplication, highlighting distinct genomic alterations in the sarcomatoid form compared to the conventional component.
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  • Spermatocytic tumors (ST) are rare, mostly benign germ cell tumors found in older men, but some can behave aggressively, especially when they transform into a sarcomatoid form.
  • In a study of 27 samples from 25 patients, researchers identified two genomic subgroups of STs: one with stable genomes and specific RAS/RAF mutations, and another with altered ploidy but no recurrent mutations.
  • Aggressive cases of ST were linked to mutations in the TP53 gene and an increase in chromosome 12p, indicating distinct biologic progression patterns within the tumor types.
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Article Synopsis
  • The differential diagnosis for oncocytic renal tumors includes both benign and aggressive forms, with a focus on distinguishing the low-grade oncocytic tumor (LOT) from other similar tumors such as oncocytoma and chromophobe RCC.
  • Recent research established that LOT has a specific immunoprofile and a high incidence of mTOR pathway mutations, with 80-100% of these tumors showing alterations.
  • In a study of 30 tumors, thorough examination techniques confirmed LOT diagnosis in 70% of cases, demonstrating strong correlation in determinate tumors (93% concordance) while categorizing others as oncytic neoplasms without specific classification.
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Rationale And Objectives: The study aims to propose an optimal workflow in patients with a PI-RADS 3 (PR-3) assessment category (AC) through determining the timing and type of pathology interrogation used for the detection of clinically significant prostate cancer (csPCa) in these men based upon a 5-year retrospective review in a large academic medical center.

Materials And Methods: This United States Health Insurance Probability and Accountability Act (HIPAA)-compliant, institutional review board-approved retrospective study included men without prior csPCa diagnosis who received PR-3 AC on magnetic resonance (MR) imaging (MRI). Subsequent incidence and time to csPCa diagnosis and number/type of prostate interventions was recorded.

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Aims: Extramammary Paget disease (EMPD) is an epithelial neoplasm that can occur at many sites, including the vulva and scrotum. EMPD is characterised by the presence of neoplastic cells, in single cells and clusters, that infiltrate all layers of non-neoplastic squamous epithelium. The differential diagnosis for EMPD includes melanoma in situ and secondary involvement of tumours from other sites, such as urothelial or cervical; pagetoid spread of tumor cells can also been seen at other sites, such as anorectal mucosa.

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Sertoli cell tumor (SCT) is the second most common type of sex cord-stromal tumor in men, and ∼10% exhibit malignant behavior. Although CTNNB1 variants have been described in SCTs, only a limited number of metastatic cases have been analyzed, and the molecular alterations associated with aggressive behavior remain largely unexplored. This study evaluated a series of nonmetastasizing and metastasizing SCTs using next-generation DNA sequencing to further characterize their genomic landscape.

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Perivascular epithelioid cell tumors (PEComas) are a distinctive group of mesenchymal neoplasms that demonstrate features of smooth muscle and melanocytic differentiation. Here, we present the clinicopathologic, immunohistochemical, and molecular features of 15 uterine sarcomas diagnosed as malignant PEComa. The median patient age was 56 years (range: 27 to 86 y).

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Long interspersed element 1 (LINE-1) open reading frame 1 protein (ORF1p) expression is a common feature of many cancer types, including high-grade serous ovarian carcinoma (HGSOC). Here, we report that ORF1p is not only expressed but also released by ovarian cancer and primary tumor cells. Immuno-multiple reaction monitoring-mass spectrometry assays showed that released ORF1p is confidently detectable in conditioned media, ascites, and patients' plasma, implicating ORF1p as a potential biomarker.

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Background There is uncertainty in the management of renal masses diagnosed as oncocytomas with image-guided percutaneous biopsy. Purpose To assess the reliability of a diagnosis of oncocytoma based on image-guided percutaneous renal mass biopsy and evaluate patient outcomes following different management strategies. Materials and Methods In this retrospective study, image-guided percutaneous biopsy pathology reports from April 2004 to April 2019 were searched for keywords "oncocytoma" and "oncocytic neoplasm" and compared with surgical pathology or repeat biopsy results.

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While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC.

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A small subset of male germ cell tumors (GCT) demonstrates overgrowth of histologic components that resemble somatic malignancies (e.g., sarcoma, carcinoma).

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Aims: Biphasic hyalinizing psammomatous (BHP) renal cell carcinoma (RCC) is a newly described emerging entity within the spectrum of papillary RCC in the WHO 2022 classification. Molecular analyses have discovered that BHP RCC consistently harbour somatic mutations in the neurofibromin 2 (NF2) gene. The NF2 gene product, merlin, is known to primarily function as a tumour suppressor.

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