Publications by authors named "Jesse Hart"

12 Publications

  • Page 1 of 1

Primary Fallopian Tube Mullerian Adenosarcoma With Sarcomatous Overgrowth and a Previously Unreported MEIS1-NCOA2 Gene Fusion.

Int J Gynecol Pathol 2021 Mar 24. Epub 2021 Mar 24.

Women & Infants Hospital (R.R.e.R., E.R.L., M.R.Q., K.H.) Department of Pathology and Laboratory Medicine, Brown University (R.R.e.R., E.R.L., J.L.H., M.R.Q., K.H.) Rhode Island Hospital (J.L.H.), Providence, Rhode Island Laboratório Cicap-Hospital Alemão Oswaldo Cruz, São Paulo, SP, Brazil (R.R.eR.).

Extrauterine Mullerian adenosarcomas (MA) are rare and often associated with endometriosis. We report a 55-yr-old patient seen in consultation for abdominal pain and bloating. Imaging was suggestive of a left adnexal mass and "peritoneal carcinomatosis". Pathological examination of the specimen revealed a MA arising in the left fallopian tube, with sarcomatous overgrowth, diffuse peritoneal involvement and omental "caking". Next-generation sequencing identified a MEIS1-NCOA2 gene fusion, previously unreported in MA.
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http://dx.doi.org/10.1097/PGP.0000000000000777DOI Listing
March 2021

The Great Imposter: A Confusing Case of a Rare Renal Cell Carcinoma.

R I Med J (2013) 2020 Dec 1;103(10):35-37. Epub 2020 Dec 1.

Associate Professor of Medicine, Clinician Educator, Warren Alpert Medical School of Brown University; Associate Program Director, Brown Internal Medicine Residencies.

We report a 61-year-old male with sarcomatoid renal cell carcinoma (sRCC) in the context of multiple paraneoplastic syndromes, including thrombocytosis, leukemoid reaction, and paraneoplastic hepatopathy (Stauffer syndrome). The patient's clinical course was complicated by multiple medical challenges, extensive metastases, and persistent infection. This confusing presentation of a rare subtype of renal cell carcinoma (RCC) highlights the diverse and often misleading manifestations of this aggressive malignancy. Clinicians should be aware of the association between RCC, multiple paraneoplastic syndromes, and its propensity to present with systemic, non-renal symptoms.
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December 2020

PAX8 Expression in Breast Cancer.

Appl Immunohistochem Mol Morphol 2021 Apr;29(4):293-298

Department of Pathology and Laboratory Medicine, Lifespan Medical Center and Brown University Alpert School of Medicine, Providence, RI.

PAX8 expression is frequently detected in renal, thyroidal, and Müllerian carcinomas, and PAX8 immunohistochemistry is often used to confirm the origin of these tumors. Tumors metastatic to the breast may masquerade as primary breast lesions. PAX8 is strongly expressed in tumors of Müllerian origin and largely negative in breast primaries, but an immunohistochemical expression of PAX8 in breast cancer has not been systematically evaluated in a large series. We analyzed 266 cases of invasive carcinoma of the breast on tissue microarrays and whole tissue sections with a PAX8 monoclonal antibody. Both the extent (focal or diffuse) and intensity (weak, moderate, or strong) of nuclear staining were assessed in the tumor cells. In total, 16 cases (6.02%) were positive for PAX8 (12 with weak and 4 with moderate staining). Expression was diffuse in 7 cases and focal in 9 cases. All 16 PAX8-positive tumors were histologic grade III invasive ductal carcinomas, 13 of these were triple-negative, 2 were HER2-positive, only and 1 was progesterone receptor-positive only. Strong PAX8 nuclear expression was not seen in any of the cases. PAX8 was negative in breast tumors with neuroendocrine features. Our study demonstrated a low rate of PAX8 expression in breast cancer. When present, PAX8 expression was only seen in high-grade invasive ductal carcinomas, mostly triple-negative. The presence of PAX8 immunoreactivity alone cannot exclude mammary origin, especially when only weak to moderate staining is observed, so the correlation with available clinical and pathologic data helps to ensure an accurate diagnosis.
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http://dx.doi.org/10.1097/PAI.0000000000000883DOI Listing
April 2021

Genomics of MPNST (GeM) Consortium: Rationale and Study Design for Multi-Omic Characterization of NF1-Associated and Sporadic MPNSTs.

Genes (Basel) 2020 04 2;11(4). Epub 2020 Apr 2.

Department of Pathology, University College London Cancer Institute, Bloomsbury, London WC1E 6BT, UK.

The Genomics of Malignant Peripheral Nerve Sheath Tumor (GeM) Consortium is an international collaboration focusing on multi-omic analysis of malignant peripheral nerve sheath tumors (MPNSTs), the most aggressive tumor associated with neurofibromatosis type 1 (NF1). Here we present a summary of current knowledge gaps, a description of our consortium and the cohort we have assembled, and an overview of our plans for multi-omic analysis of these tumors. We propose that our analysis will lead to a better understanding of the order and timing of genetic events related to MPNST initiation and progression. Our ten institutions have assembled 96 fresh frozen NF1-related (63%) and sporadic MPNST specimens from 86 subjects with corresponding clinical and pathological data. Clinical data have been collected as part of the International MPNST Registry. We will characterize these tumors with bulk whole genome sequencing, RNAseq, and DNA methylation profiling. In addition, we will perform multiregional analysis and temporal sampling, with the same methodologies, on a subset of nine subjects with NF1-related MPNSTs to assess tumor heterogeneity and cancer evolution. Subsequent multi-omic analyses of additional archival specimens will include deep exome sequencing (500×) and high density copy number arrays for both validation of results based on fresh frozen tumors, and to assess further tumor heterogeneity and evolution. Digital pathology images are being collected in a cloud-based platform for consensus review. The result of these efforts will be the largest MPNST multi-omic dataset with correlated clinical and pathological information ever assembled.
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http://dx.doi.org/10.3390/genes11040387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231181PMC
April 2020

Anti-miRNA Oligonucleotide Therapy for Chondrosarcoma.

Mol Cancer Ther 2019 11 24;18(11):2021-2029. Epub 2019 Jul 24.

Department of Orthopaedics, Warren Alpert Medical School of Brown University and Rhode Island Hospital, Providence, Rhode Island.

Chondrosarcoma is a highly aggressive primary malignant bone tumor mostly occurring in adults. There are no effective systemic treatments, and patients with this disease have poor survival. miR-181a is an oncomiR that is overexpressed in high-grade chondrosarcoma and promotes tumor progression. Regulator of G-protein signaling 16 (RGS16) is a target of miR-181a. Inhibition of RGS16 expression by miR-181a enhances CXC chemokine receptor 4 signaling, which in turn increases MMP1 and VEGF expression, angiogenesis, and metastasis. Here, we report the results of systemic treatment with anti-miRNA oligonucleotides (AMO) directed against miR-181a utilizing a nanopiece delivery platform (NPs). NPs were combined with a molecular beacon or anti-miR-181a oligonucleotides and are shown to transfect chondrosarcoma cells and Intratumoral injection and systemic delivery had similar effects on miR-181a expression in nude mice bearing chondrosarcoma xenografts. Systemic delivery of NPs carrying anti-miR-181a also restored expression, decreased expression of VEGF and MMP1, MMP activity, and tumor volume by 32% at day 38, and prolonged survival from 23% to 45%. In conclusion, these data support that systemic delivery of AMO shows promise for chondrosarcoma treatment.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-1020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825546PMC
November 2019

A case of recurrent desmoplastic malignant melanoma presenting as empyema with underlying lung mass.

J Surg Case Rep 2016 Apr 22;2016(4). Epub 2016 Apr 22.

The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA Department of Surgery, Rhode Island Hospital, Brown University, Providence, RI 02903, USA.

Desmoplastic malignant melanoma (DMM) is an extremely rare subtype of cutaneous melanoma that has diverse clinical presentations. We describe the unique case of a 57-year-old man presenting with empyema secondary to vascular occlusion from metastatic DMM. Only two other cases of DMM presenting as a lung mass have been previously reported in the literature. This report highlights potential insidious pathology of DMM, which requires a high clinical suspicion to properly diagnose and manage.
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http://dx.doi.org/10.1093/jscr/rjw029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841566PMC
April 2016

Epithelioid Schwannomas: An Analysis of 58 Cases Including Atypical Variants.

Am J Surg Pathol 2016 May;40(5):704-13

*Department of Pathology, Rhode Island Hospital, Brown University, Providence, RI †Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR ‡Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.

The histologic features and outcome of 58 cases of epithelioid schwannoma were studied to determine the significance of atypical histologic features. Cases were retrieved from personal consultation files from 1999 to 2013. Patients (31 male and 26 female patients) ranged in age from 14 to 80 years (median, 38 y). Two patients had schwannomatosis 1. Tumors developed in the dermis/subcutis (n=56) or muscle (n=2) of the upper extremity (34.5%), lower extremity (34.5%), thorax/abdomen/back (18%), and less common anatomic locations including the scalp, neck, lip, and breast. They ranged in size from 0.25 to 4.5 cm (median, 2.0 cm). Typically circumscribed and surrounded by a perineurium, they comprised single or small groups of epithelioid schwann cells with a moderate amphophilic cytoplasm and occasional nuclear pseudoinclusions. Stroma varied from myxoid to hyalinized, often with thick-walled vessels (55 cases). Mitotic rate ranged from 0 to 9 mitoses/10 high-power field (HPF) (2.37 mm) in the most active areas (mean, 2 to 3 mitoses/10 HPFs). Thirteen cases (22%) were "atypical," defined by a high mitotic rate (≥3 mitoses per 10 HPFs) and nuclear size variation (≥3:1). All (56/56) expressed S100 protein; type IV collagen invested groups or individual cells (16/17). Melanoma markers were negative, except for melan A (1 case). Follow-up in 39 patients (median, 78 mo; range, 6 to 174 mo) indicated that 31 (79%) were alive without disease (including 9/13 atypical cases; median, 78 mo), 7 (18%) were alive with unknown status, and 1 patient had died of unrelated causes. One tumor recurred, but none metastasized. Epithelioid schwannomas, even those with atypical features, are benign and do not constitute a histologic continuum with epithelioid malignant peripheral nerve sheath tumors, which typically occur in deep soft tissues and have more anaplastic features.
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http://dx.doi.org/10.1097/PAS.0000000000000589DOI Listing
May 2016

PET/CT Helps Downgrade an Aggressive-Appearing Rib Mass to a Probable Benign Lesion in a 9-Year-Old Girl.

Clin Nucl Med 2016 Mar;41(3):221-3

From the *The Warren Alpert Medical School of Brown University; and Departments of †Diagnostic Imaging, and ‡Pathology and Laboratory Medicine, The Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.

We present a case of a 9-year-old girl with no significant medical history who developed acute onset of shortness of breath and upper chest pain during cheerleading practice. Laboratory results and physical examination were unremarkable. Chest radiograph and chest CT showed an expansile lytic aggressive-appearing mass within the left sixth rib. Subsequent F-FDG PET/CT showed a left sixth rib lesion that was not hypermetabolic and appeared benign. Biopsy yielded a diagnosis of enchondroma, a benign intramedullary tumor that accounts for 24% of all bone tumors in children as well as adolescents.
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http://dx.doi.org/10.1097/RLU.0000000000001028DOI Listing
March 2016

Vascular tumors of bone.

Semin Diagn Pathol 2014 Jan 7;31(1):30-8. Epub 2014 Jan 7.

Department of Pathology, University of Arkansas for Medical Sciences, 4301 W. Markham St, #517 Little Rock, Arkansas 72205. Electronic address:

Vascular tumors of the bone represent a variety of neoplasms, ranging from benign hemangiomas and epithelioid hemangiomas to intermediate grade hemangioendotheliomas to frankly malignant angiosarcomas. Over the years, there has been considerable debate concerning the aggressivity, nomenclature, and mere existence of various nosologic entities, due to morphologic similarities and uncertainty regarding biologic behavior. Such debate has led to confusion among pathologists and clinicians, thus diminishing the prognostic implications in the diagnosis of these lesions. Here we review the current knowledge concerning the primary vascular neoplasms of the bone and correlate clinicopathologic features with tumor behavior.
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http://dx.doi.org/10.1053/j.semdp.2014.01.003DOI Listing
January 2014

Breast cancer: assessing response to neoadjuvant chemotherapy by using US-guided near-infrared tomography.

Radiology 2013 Feb 21;266(2):433-42. Epub 2012 Dec 21.

Biomedical Engineering Program, Electrical and Computer Engineering Department, University of Connecticut, 371 Fairfield Rd, U2157, Storrs, CT 06269, USA.

Purpose: To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response.

Materials And Methods: The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons.

Results: There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively).

Discussion: These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.
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http://dx.doi.org/10.1148/radiol.12112415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558877PMC
February 2013

IMP3 immunocytochemical staining increases sensitivity in the routine cytologic evaluation of biliary brush specimens.

Diagn Cytopathol 2012 Apr 22;40(4):321-6. Epub 2010 Nov 22.

Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT 06102-8000, USA.

Biliary brush cytology is an important diagnostic tool in the evaluation of biliary strictures. Here, we evaluated 64 patients with biliary strictures who underwent endoscopic retrograde cholangiopancreatography with bile duct brushings. We assessed the utility of combining routine Papanicolaou-stained cytologic evaluation with immunocytochemical expression of insulin-like growth factor mRNA-binding protein-3 (IMP3). Definitive diagnoses were obtained via tissue resection/autopsy, biopsy, fine needle aspiration, or clinical progression of disease. Thirty-nine of the 64 patients were ultimately diagnosed with malignancy. The sensitivity of routine cytology for the detection of malignancy was 33.3%, immunocytochemical-IMP3 expression was 64.1%, and the combined sensitivity was 71.8%. The specificity of each method was 100%. The sensitivity of IMP3 immunocytochemical staining in the detection of malignancy in biliary brushings was superior to routine PAP-stained cytologic evaluation. Moreover, the combined use of biliary brushing cytology and IMP3 immunohistochemistry proved superior to the use of either method alone.
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http://dx.doi.org/10.1002/dc.21571DOI Listing
April 2012

Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis.

Arch Pathol Lab Med 2011 Feb;135(2):268-72

Department of Pathology and Laboratory Medicine, Hartford Hospital, Connecticut 06102-8000, USA.

Epithelioid angiosarcoma is a highly aggressive endothelial cell malignancy, most commonly arising in the deep soft tissues, but a variety of primary sites, including the adrenals, thyroid, skin, and bone, are encountered. On hematoxylin-eosin-stained sections, the pathologist encounters sheets of large, mildly to moderately pleomorphic epithelioid cells, with abundant eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. Obvious vasoformative foci may not be present, creating confusion with metastatic carcinomas, malignant mesothelioma, melanoma, anaplastic lymphoma, epithelioid peripheral nerve sheath malignancies, and epithelioid sarcoma. Moreover, malignancies with apparent vascular differentiation must be distinguished from less aggressive vascular neoplasms, including epithelioid hemangioendothelioma. Given the range of clinical presentation, the diversity of primary sites, and the nonspecific initial histopathologic appearance, here we review the histologic findings and immunohistochemical profiles of epithelioid angiosarcoma and neoplasms in its differential diagnosis.
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http://dx.doi.org/10.1043/1543-2165-135.2.268DOI Listing
February 2011