Base of tongue neuroendocrine carcinoma: A case report.

Neuroendocrine tumors are rare entities in the head and neck and an even more rare entity in the tongue. In this case report, we describe a calcified neuroendocrine tumor of the base of tongue that was presumed to be benign and was electively excised with pathology demonstrating low-grade carcinoma with focal neuroendocrine features and extensive ossification. We then discuss the histopathology and management.

Blastocyst development after fertilization with in vitro spermatids derived from nonhuman primate embryonic stem cells.

OBJECTIVE: To demonstrate that functional spermatids can be derived in vitro from nonhuman primate pluripotent stem cells. DESIGN: Green fluorescent protein-labeled, rhesus macaque nonhuman primate embryonic stem cells (nhpESCs) were differentiated into advanced male germ cell lineages using a modified serum-free spermatogonial stem cell culture medium. In vitro-derived round spermatid-like cells (rSLCs) from differentiated nhpESCs were assessed for their ability to fertilize rhesus oocytes by intracytoplasmic sperm(atid) injection. SETTING: Multiple academic laboratory settings. PATIENTS: Not applicable. INTERVENTIONS: Intracytoplasmic sperm(atid) injection of in vitro-derived spermatids from nhpESCs into rhesus macaque oocytes. MAIN OUTCOME MEASURES: Differentiation into spermatogenic cell lineages was measured through multiple assessments including ribonucleic acid sequencing and immunocytochemistry for various spermatogenic markers. In vitro spermatids were assessed for their ability to fertilize oocytes by intracytoplasmic sperm(atid) injection by assessing early fertilization events such as spermatid deoxyribonucleic acid decondensation and pronucleus formation/apposition. Preimplantation embryo development from the one-cell zygote stage to the blastocyst stage was also assessed. RESULTS: Nonhuman primate embryonic stem cells can be differentiated into advanced germ cell lineages, including haploid rSLCs. These rSLCs undergo deoxyribonucleic acid decondensation and pronucleus formation/apposition when microinjected into rhesus macaque mature oocytes, which, after artificial activation and coinjection of ten-eleven translocation 3 protein, undergo embryonic divisions with approximately 12% developing successfully into expanded blastocysts. CONCLUSIONS: This work demonstrates that rSLCs, generated in vitro from primate pluripotent stem cells, mimic many of the capabilities of in vivo round spermatids and perform events essential for preimplantation development. To our knowledge, this work represents, for the first time, that functional spermatid-like cells can be derived in vitro from primate pluripotent stem cells.

Subjective and Objective Measurements of Sinonasal Manifestations in Patients With Autoimmune Disorders.

OBJECTIVES/HYPOTHESIS: A number of autoimmune disorders (ADs) are associated with a spectrum of sinonasal manifestations comparable to chronic rhinosinusitis (CRS). Our objective was to study the subjective and objective measurements of sinonasal manifestations of ADs. STUDY DESIGN: Retrospective cohort study. METHODS: All patients with ADs referred to our tertiary care rhinology clinic from 2008 to 2019 with sinonasal symptoms were compared to randomly selected cohorts of noneosinophilic CRS without nasal polyps (neCRSsNP) and eosinophilic CRSsNP (eCRSsNP). Demographic data, along with the 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Kennedy (LK) endoscopy score, Lund-Mackay (LM) computed tomography (CT) score, nasal crusting, and epistaxis were reviewed at presentation. RESULTS: Fifty-three patients with an AD (26 with sarcoidosis, 14 with systemic lupus erythematosus, 10 with granulomatosis with polyangiitis [GPA], and three with pemphigoid vulgaris) were identified, and compared to 75 randomly selected neCRSsNP patients and 75 eCRSsNP patients. Patients with an AD had an average SNOT-22 score of 44.4 (confidence interval [CI]: 34.6-51.2) compared to 25 (CI: 24.4-25.1) and 29.7 (CI: 20.3-29.7) for neCRSsNP and eCRSsNP patients, respectively (P < .0001), and an average LK endoscopy score of 5.3 (CI: 4.3-6.3), compared to 3.4 (P = .005, CI: 2.7-4) in neCRSsNP and 4.4 in eCRSsNP (P = .2, CI: 3.7-5). There was no significant difference in the CT score compared to both groups. Patients with an AD also scored significantly worse on all four SNOT-33 subdomains, nasal obstruction, nasal crusting, and epistaxis. Additionally, patients with GPA had the worst symptomatic and endoscopy scores. CONCLUSIONS: Patients with ADs presenting with sinonasal symptoms have a more severe subjective and objective presentation than patients with CRS without nasal polyps. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:255-259, 2021.

Sinonasal Anatomic Variants in Allergic Fungal Rhinosinusitis.

BACKGROUND: The pathophysiology of allergic fungal rhinosinusitis (AFRS) is not well understood. OBJECTIVES: To study the incidence of sinonasal anatomic variants (AVs) in AFRS. METHODS: Retrospective cohort study. Patients with AFRS presenting to our clinic from 2008 to 2018 were reviewed for laterality of the disease. Patients with unilateral involvement were further studied for AV presence by reviewing their preoperative sinus CT scan at original presentation. Each patient's uninvolved side served as its own control. AVs studied include agger nasi (AN), Haller's cells (HC), concha bullosa (CB) and supraorbital ethmoid cells (SOEC). RESULTS: A total of 155 patients with AFRS were identified. 30 patients (19.3%) had unilateral disease involvement. Of these, 16 patients had left sided and 14 patients had right sided disease. AV were present in 26 of the 30 AFRS sides (86.7%) and in 21 of the 30 healthy sides (70%), (chi squared = 2.45, p = 0.117). CB were present in 12 of 30 AFRS sides (40%) and only in 1 of 30 healthy sides (3%), (chi squared = 11.88, p = 0.0006). The presence of HC was more common in the AFRS vs healthy sides (7 of 30, 23.3% vs 2 of 30, 6.7%, respectively, p = 0.071). AN and SOEC presence was similar in both AFRS and healthy sides (p = 0.598 and p = 0.718 respectively). CONCLUSION: AV are more common on the sides with AFRS compared to healthy sides, with the presence of CB reaching unquestionable statistical significance. Further study is needed to determine the possible association of AV, especially concha bullosa, with the pathophysiology of AFRS.

Per- and polyfluoroalkyl substances impact human spermatogenesis in a stem-cell-derived model.

Per- and polyfluoroalkyl substances (PFASs) represent a highly ubiquitous group of synthetic chemicals used in products ranging from water and oil repellents and lubricants to firefighting foam. These substances can enter and accumulate in multiple tissue matrices in up to 100% of people assessed. Though animal models strongly identify these compounds as male reproductive toxicants, with exposed rodents experiencing declines in sperm count, alterations in hormones, and DNA damage in spermatids, among other adverse outcomes, human studies report conflicting conclusions as to the reproductive toxicity of these chemicals. Using an innovative, human stem-cell-based model of spermatogenesis, we assessed the effects of the PFASs perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and a mixture of PFOS, PFOA, and PFNA for their impacts on human spermatogenesis in vitro under conditions relevant to the general and occupationally exposed populations. Here, we show that PFOS, PFOA, PFNA, and a mixture of PFOS, PFOA, and PFNA do not decrease in vitro germ cell viability, consistent with reports from human studies. These compounds do not affect mitochondrial membrane potential or increase reactive oxygen species generation, and they do not decrease cell viability of spermatogonia, primary spermatocytes, secondary spermatocytes, or spermatids in vitro under the conditions examined. However, exposure to PFOS, PFOA, and PFNA reduces expression of markers for spermatogonia and primary spermatocytes. While not having direct effects on germ cell viability, these effects suggest the potential for long-term impacts on male fertility through the exhaustion of the spermatogonial stem cell pool and abnormalities in primary spermatocytes. ABBREVIATIONS: CDC: Centers for Disease Control; DMSO: dimethyl sulfoxide; GHR: growth hormone receptor; hESCs: human embryonic stem cells; PFASs: per- and polyfluoroalkyl substances; PFCs: perfluorinated compounds; PFNA: perfluorononanoic acid; PFOS: perfluorooctanesulfonic acid; PFOA: perfluorooctanoic acid; PLZF: promyelocytic leukemia zinc finger; ROS: reactive oxygen species; HILI: RNA-mediated gene silencing 2; SSC: spermatogonial stem cell.

Ubiquitous Flame-Retardant Toxicants Impair Spermatogenesis in a Human Stem Cell Model.

Sperm counts have rapidly declined in Western males over the past four decades. This rapid decline remains largely unexplained, but exposure to environmental toxicants provides one potential explanation for this decline. Flame retardants are highly prevalent and persistent in the environment, but many have not been assessed for their effects on human spermatogenesis. Using a human stem cell-based model of spermatogenesis, we evaluated two major flame retardants, hexabromocyclododecane (HBCDD) and tetrabromobisphenol A (TBBPA), under acute conditions simulating occupational-level exposures. Here we show that HBCDD and TBBPA are human male reproductive toxicants in vitro. Although these toxicants do not specifically affect the survival of haploid spermatids, they affect spermatogonia and primary spermatocytes through mitochondrial membrane potential perturbation and reactive oxygen species generation, ultimately causing apoptosis. Taken together, these results show that HBCDD and TBBPA affect human spermatogenesis in vitro and potentially implicate this highly prevalent class of toxicants in the decline of Western males' sperm counts.