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TSC2-mutant uterine sarcomas with JAZF1-SUZ12 fusions demonstrate hybrid features of endometrial stromal sarcoma and PEComa and are responsive to mTOR inhibition

Chiang, Sarah; Vasudevaraja, Varshini; Serrano, Jonathan; Stewart, Colin J R; Oliva, Esther; Momeni-Boroujeni, Amir; Jungbluth, Achim A; Da Cruz Paula, Arnaud; da Silva, Edaise M; Weigelt, Britta; Park, Kay J; Soslow, Robert A; Murali, Rajmohan; Ellenson, Lora H; Benayed, Ryma; Ladanyi, Marc; Abu-Rustum, Nadeem R; Dickson, Mark A; Cohen, Seth; Aghajanian, Carol; Hensley, Martee L; Lee, Cheng-Han; Snuderl, Matija; Konner, Jason A
Uterine perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm that occasionally shares morphologic and immunohistochemical overlap with low- and high-grade endometrial stromal sarcoma (LGESS and HGESS). In this study, we sought to characterize the clinical, morphologic, genetic, and epigenetic features of five uterine sarcomas that display histologic features of LGESS, HGESS, and PEComa. All tumors demonstrated epithelioid cells often associated with a low-grade spindled component resembling LGESS, with both regions expressing CD10, ER, PR, variable HMB45, and Melan-A immunoreactivity, and strong cathepsin K and pS6 expression. Targeted massively parallel sequencing analysis revealed the presence of somatic TSC2 mutations in all five cases, of which four harbored concurrent or consecutive JAZF1-SUZ12 gene fusions. Unsupervised hierarchical clustering analysis of methylation profiles of TSC2-mutant uterine sarcomas (n = 4), LGESS (n = 10), and HGESS (n = 12) demonstrated two clusters consisting of (1) all LGESS and TSC2-mutant uterine sarcomas and (2) all HGESS. KEGG pathway analysis detected methylation differences in genes involved in PI3K/AKT, calcium, and Rap1 signaling. TSC2-mutant uterine sarcomas were responsive to hormone suppression, and mTOR inhibition demonstrated clinical benefit in four patients with these neoplasms. Our results suggest that these tumors represent histologically distinctive LGESS with TSC2 mutations. TSC2 mutations and JAZF1-SUZ12 fusion may help diagnose these tumors and possibly direct effective treatment.
PMID: 34561551
ISSN: 1530-0285
CID: 5067362

COVID-19 outcomes of patients with gynecologic cancer in New York City: An updated analysis from the initial surge of the pandemic

Lara, Olivia D; Smith, Maria; Wang, Yuyan; O'Cearbhaill, Roisin E; Blank, Stephanie V; Kolev, Valentin; Carr, Caitlin; Knisely, Anne; McEachron, Jennifer; Gabor, Lisa; Chapman-Davis, Eloise; Cohen, Seth; Fehniger, Julia; Lee, Yi-Chun; Isani, Sara; Liu, Mengling; Wright, Jason D; Pothuri, Bhavana
BACKGROUND:Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS:Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS:Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS:The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.
PMCID:8648583
PMID: 34922769
ISSN: 1095-6859
CID: 5087132

Diagnosis and Treatment of Peyronie Disease With Both Dorsal and Ventral Plaques Using Doppler Ultrasound: NYU Case of the Month, July 2019

Cohen, Seth D
PMCID:6864913
PMID: 31768141
ISSN: 1523-6161
CID: 4215772

Diagnosis and Treatment of Persistent Genital Arousal Disorder

Cohen, Seth D
PMCID:5811885
PMID: 29472831
ISSN: 1523-6161
CID: 3061512

The Challenge of Erectile Dysfunction Management in the Young Man

Cohen, Seth D
Erectile dysfunction (ED) in a young man is an important health problem that significantly impacts the patient's quality of life and can have a detrimental effect on his well-being and relationship with his partner. Erectile dysfunction or impotence is one of the few disorders that will bring a young man into the doctor's office. This review article focuses on the epidemiology, etiology, presentation, work-up, and treatment of young men (age ~20-40 years old) presenting with complaints of ED. It is important to identify the precise etiology of the ED before proceeding with further evaluation and treatment because the work-up can be invasive and costly. ED is estimated to affect 20 % of men above 40 years of age, with the incidence increasing with increasing age. Erectile dysfunction has traditionally been seen as an age-dependent problem; however, approximately 2 % of men are affected at 40 years of age but this may be a gross underestimation secondary to reporting bias. Because ED is traditionally seen in the aging male population, studies regarding ED tend to be more frequently carried out among middle-aged and elderly men rather than in young men. These studies underline how comorbidities such as diabetes mellitus, cardiovascular or neurological pathologies, and medication use are strongly linked with ED. In addition, ED has been described to be associated with obesity or physical inactivity. This review article summarizes the important information that all sexual medicine providers should be familiar with when diagnosing, counseling, and treating young men with erectile dysfunction.
PMID: 26563194
ISSN: 1534-6285
CID: 1934692

PERSISTENT GENITAL AROUSAL DISORDER (PGAD): EXPERIENCE WITH MANAGEMENT IN 35 CONSECUTIVE CASES [Meeting Abstract]

Cohen, SD; Gonzalez, JR; Gagnon, C; Minton, JN; Espenschied, C; Goldstein, I
ISI:000352789100119
ISSN: 1743-6109
CID: 2509912

OBSERVATION OF LOCAL CLINICAL PENILE PROSTHESES INFECTIONS INSTEAD OF IMMEDIATE SALVAGE RESCUE/REMOVAL: TEN CENTER STUDY WITH SURPRISING RESULTS [Meeting Abstract]

Henry, G; Price, G; Pryor, M; Greenfield, J; Jones, L; Perito, P; Morey, A; Goldstein, I; Bella, A; Kohler, T; Land, S; Berger, A; Cohen, S
ISI:000352789100093
ISSN: 1743-6109
CID: 2509892

SYMPTOMATIC AND ASYMPTOMATIC BARTHOLIN CYST FORMATION AFTER COMPLETE VESTIBULECTOMY FOR CONGENITAL OR ACQUIRED NEUROPROLIFERATIVE VESTIBULODYNIA [Meeting Abstract]

Cohen, SD; Gonzalez, JR; Gagnon, C; Minton, JN; Espenschied, C; Goldstein, I
ISI:000352789100114
ISSN: 1743-6109
CID: 2509902

5 ALPHA REDUCTASE ENZYME DEFICIENCY: A NEW PATHOPHYSIOLOGY OF FEMALE SEXUAL DYSFUNCTION [Meeting Abstract]

Cohen, SD; Gonzalez, JR; Gagnon, C; Minton, JN; Espenschied, C; Goldstein, I
ISI:000352789100003
ISSN: 1743-6109
CID: 2509882

5 ALPHA-REDUCTASE ENZYME DEFICIENCY: A NEW PATHOPHYSIOLOGY OF FEMALE HYPOACTIVE SEXUAL DESIRE DISORDER [Meeting Abstract]

Cohen, S; Gagnon, C; Minton, J; Goldstein, I
ISI:000348731500163
ISSN: 1743-6109
CID: 2509872