Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Importance: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. Objective: To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). Design, Setting, and Participants: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Main Outcomes and Measures: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Results: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). Conclusions and Relevance: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

Circulating trophoblast cell clusters for early detection of placenta accreta spectrum disorders.

Placenta accreta spectrum (PAS) is a high-risk obstetrical condition associated with significant morbidity and mortality. Current clinical screening modalities for PAS are not always conclusive. Here, we report a nanostructure-embedded microchip that efficiently enriches both single and clustered circulating trophoblasts (cTBs) from maternal blood for detecting PAS. We discover a uniquely high prevalence of cTB-clusters in PAS and subsequently optimize the device to preserve the intactness of these clusters. Our feasibility study on the enumeration of cTBs and cTB-clusters from 168 pregnant women demonstrates excellent diagnostic performance for distinguishing PAS from non-PAS. A logistic regression model is constructed using a training cohort and then cross-validated and tested using an independent cohort. The combined cTB assay achieves an Area Under ROC Curve of 0.942 (throughout gestation) and 0.924 (early gestation) for distinguishing PAS from non-PAS. Our assay holds the potential to improve current diagnostic modalities for the early detection of PAS.

Benefits of Continuous Positive Airway Pressure (CPAP) During Radiation Therapy: A Prospective Trial.

PURPOSE: This study aimed to study the impact of continuous positive airway pressure (CPAP) on chest anatomy and tumor motion in patients receiving radiation therapy. METHODS AND MATERIALS: Patients with primary or secondary lung tumors, left-sided breast cancer, or liver metastases referred for radiation therapy were trained to breathe with a CPAP device using a face mask to a maximal pressure of 15 cm H2O. Three- and 4-dimensional computed tomography simulation was performed twice for each patient: once with free breathing (FB) and again using CPAP. Volumetric and dosimetric parameters of treatment plans were compared. RESULTS: Forty-nine patients were enrolled, of whom 6 withdrew consent before simulation and 3 withdrew because of discomfort. Thus, a total of 40 patients were analyzed. Twenty-seven patients (67.5%) were treated with CPAP based on confirmation of the volumetric or dosimetric benefit of CPAP. Mean lung volume increased by 37% (P < .001). The mean augmentation was 1283 ± 1128 cm3 (CPAP vs FB; P = .0006) in patients with normal lung function tests and 719 ± 341 cm3 (P = .003) in patients with a restrictive pattern. Increased lung volume was independent of age, body mass index, sex, chronic obstructive pulmonary disease, smoking status, and heart disease. Tumor motion in the lung was decreased as reflected in a mean reduction of planning target volume by 19% (P < .001). The greatest reduction of tumor trajectory and planning target volume occurred in tumors in the lower lung, particularly in the range of up to 6 cm above the dome of the diaphragm. The mean lung dose was reduced by 15%, lung V20 by 20%, lung V5 by 11%, and heart V5 by 16% (P < .01). CONCLUSIONS: In this prospective trial, the use of CPAP was associated with significant volumetric and dosimetric benefits compared with FB. CPAP was safe, simple to implement, and well tolerated by most patients, and it should be studied further as a method to reduce the risk of lung and heart toxicity.

A History of Board Certification in Pediatric Pathology on Its 30th Anniversary.

In 1983 under the leadership of Dr. Daria Haust, the Pediatric Pathology Club (PPC; forerunner of the Society for Pediatric Pathology [SPP]), promulgated bylaws that included recognition of the special expertise required in pediatric pathology. This standard followed formal discussion that began as early as 1970, suggesting that special certification should be pursued, and the idea was vetted by the PPC in 1980 following a special report by Dr. Benjamin Landing and a letter to PPC members. Under the leadership of Dr. William Donnelly in 1984, a relationship between the SPP and the American Board of Pathology (ABPath) began in order to receive recognition of pediatric pathology as a special discipline. As a result, a test committee chaired by Dr. Jerald Schenken began preparing question categories and examples for ABPath examination. These efforts culminated in the first pediatric pathology subspecialty examination, held in Atlanta, Georgia on November 20, 1990. With this article we wish to detail the history of ABPath pediatric pathology board certification from its beginnings to the current time.

Massive infantile myofibromatosis of the upper lip causing airway distress in a newborn.

Infantile myofibromatosis is a rare condition characterized by benign spindle cell tumors most commonly involving the head, neck, and chest. An infant female with a prenatal diagnosis of a large facial mass was delivered via Cesarean at 34 weeks. Sparse prenatal care was received. Following delivery, the neonate was found to have an 8 cm ulcerative mass involving the upper lip and philtrum. Respiratory distress developed, and mask ventilation was difficult secondary to the size of the mass. The patient was successfully intubated after numerous attempts and then transferred to the children's hospital. Additional imaging demonstrated similar masses within bilateral iliopsoas and gluteal muscles, and her right gastrocnemius. A biopsy confirmed infantile myofibromatosis. At two weeks of life, she underwent resection with bilateral myocutaneous advancement flaps and successful extubation. She received adjuvant vinblastine and methotrexate for her pelvic and extremity disease with excellent response. We present the first case of airway distress secondary to myocutaneous myofibromatosis.

Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

Intraosseous mucoepidermoid carcinoma: Outcome review.

OBJECTIVE: Identify the effect of patient characteristics, disease traits, and treatment modality on patient outcomes in the rare disease process of intraosseous mucoepidermoid carcinoma. STUDY DESIGN: Retrospective review of institutional case records and literature. METHODS: This study includes one case report, a literature review of the MEDLINE database from 1950 through June 2017 using keywords "intraosseous" and "mucoepidermoid," and a query of the University of California, Los Angeles, Department of Pathology database for all documented cases of intraosseous mucoepidermoid carcinoma of the head and neck. RESULTS: Indicators of poorer prognosis were male gender (P = 0.0071) and higher histological grade (P = 0.0095). Lesion site, size, association with odontogenic cyst, and treatment type did not have a statistically significant correlation with patient outcomes. There also was no statistically significant correlation observed between treatment modality and recurrent or progressive disease when stratified by histological grade of the cancer. CONCLUSION: This study identified male gender and high histological tumor grade as poor prognostic indicators; however, it did not reveal a statistically significant relationship between treatment modality and patient outcomes. Data regarding patient outcomes following treatment was limited due to loss to follow-up, suggesting that further investigation is required. Based on this review, decisions regarding treatment should be clinically guided and individually tailored to the patient's baseline health, disease severity, and the patient's treatment goals. A multi-disciplinary conference, as was utilized in the presented case report, may be the best approach to treatment planning for these patients at this time. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1083-1092, 2018.

Continuous Positive Airway Pressure for Motion Management in Stereotactic Body Radiation Therapy to the Lung: A Controlled Pilot Study.

OBJECTIVE: To determine the effect of continuous positive airway pressure (CPAP) on tumor motion, lung volume, and dose to critical organs in patients receiving stereotactic body radiation therapy (SBRT) for lung tumors. METHODS AND MATERIALS: After institutional review board approval in December 2013, patients with primary or secondary lung tumors referred for SBRT underwent 4-dimensional computed tomographic simulation twice: with free breathing and with CPAP. Tumor excursion was calculated by subtracting the vector of the greatest dimension of the gross tumor volume (GTV) from the internal target volume (ITV). Volumetric and dosimetric determinations were compared with the Wilcoxon signed-rank test. CPAP was used during treatment if judged beneficial. RESULTS: CPAP was tolerated well in 10 of the 11 patients enrolled. Ten patients with 18 lesions were evaluated. The use of CPAP decreased tumor excursion by 0.5 ± 0.8 cm, 0.4 ± 0.7 cm, and 0.6 ± 0.8 cm in the superior-inferior, right-left, and anterior-posterior planes, respectively (P ≤ .02). Relative to free breathing, the mean ITV reduction was 27% (95% confidence interval [CI] 16%-39%, P<.001). CPAP significantly augmented lung volume, with a mean absolute increase of 915 ± 432 cm(3) and a relative increase of 32% (95% CI 21%-42%, P=.003), contributing to a 22% relative reduction (95% CI 13%-32%, P=.001) in mean lung dose. The use of CPAP was also associated with a relative reduction in mean heart dose by 29% (95% CI 23%-36%, P=.001). CONCLUSION: In this pilot study, CPAP significantly reduced lung tumor motion compared with free breathing. The smaller ITV, the planning target volume (PTV), and the increase in total lung volume associated with CPAP contributed to a reduction in lung and heart dose. CPAP was well tolerated, reproducible, and simple to implement in the treatment room and should be evaluated further as a novel strategy for motion management in radiation therapy.

Juvenile xanthogranuloma presenting as a testicular mass in infancy: a clinical and pathologic study of three cases.

Juvenile xanthogranulomas (JXG) is a histiocytic disorder whose most common clinical presentation is a solitary cutaneous nodule in a child under 5 years of age, but it has come to be recognized that solitary extracutaneous lesions may present in a number of sites, including the soft tissues and various organs. Involvement of the genitourinary tract has been documented in children with multifocal or systemic JXG. The current report describes our experience with 3 cases of JXG presenting as a solitary mass in the testicle of infants between 2.5 and 13 months without manifestations of JXG elsewhere. The masses were intratesticular and had an infiltrative pattern of interstitial growth by mononuclear, histiocyte-like cells with replacement of seminiferous tubules and involvement of the epididymis whose pattern resembled leukemic and lymphomatous involvement of the testis. Because extracutaneous lesions of JXG may have few or no Touton giant cells, immunohistochemistry is an important adjunct to the histopathologic diagnosis. One of the previous 2 cases in the literature of JXG of the testis recurred after partial resection without an orchiectomy. Neither of the 2 youngest patients has experienced a local recurrence of JXG elsewhere in excess of 1 year since the original orchiectomy. The oldest patient, who was treated with partial orchiectomy, remains free of recurrence after 3 months of follow-up. Though uncommon, JXG joins several other distinctive neoplasms presenting in the infantile testis.

Orbital melanotic neuroectodermal tumor of infancy successfully treated with chemotherapy and subtotal excision.

Melanotic neuroectodermal tumor of infancy is a rare condition that typically presents within the first 6 months of life. It rarely metastasizes but is locally aggressive. Melanotic neuroectodermal tumor of infancy has been reported under several other names including retinal anlage tumor and melanotic progonoma. Most commonly, melanotic neuroectodermal tumor of infancy originates in the maxilla. Tumors in previously reported orbital cases have arisen from adjacent structures or from orbital bone. Recommended treatment of melanotic neuroectodermal tumor of infancy has consisted of complete excision with wide tissue margins, although success has been reported after incomplete resection. For those patients in whom surgical resection is not possible, various chemotherapy approaches have been reported with mixed results ranging from failure to sustained tumor regression. We report a case of orbital melanotic neuroectodermal tumor of infancy adherent to sclera and successfully treated with chemotherapy and subtotal excision.