Spatial Distribution of Macrophage and Lymphocyte Subtypes within Tumor Microenvironment to Predict Recurrence of Non-Muscle-Invasive Papillary Urothelial Carcinoma after BCG Immunotherapy.

Non-muscle-invasive papillary urothelial carcinoma (NMIPUC) of the urinary bladder is the most common type of bladder cancer. Intravesical Bacille Calmette-Guerin (BCG) immunotherapy is applied in patients with a high risk of recurrence and progression of NMIPUC to muscle-invasive disease. However, the tumor relapses in about 30% of patients despite the treatment, raising the need for better risk stratification. We explored the potential of spatial distributions of immune cell subtypes (CD20, CD11c, CD163, ICOS, and CD8) within the tumor microenvironment to predict NMIPUC recurrence following BCG immunotherapy. Based on analyses of digital whole-slide images, we assessed the densities of the immune cells in the epithelial-stromal interface zone compartments and their distribution, represented by an epithelial-stromal interface density ratio (IDR). While the densities of any cell type did not predict recurrence, a higher IDR of CD11c (HR: 0.0012, p-value = 0.0002), CD8 (HR: 0.0379, p-value = 0.005), and ICOS (HR: 0.0768, p-value = 0.0388) was associated with longer recurrence-free survival (RFS) based on the univariate Cox regression. The history of positive repeated TUR (re-TUR) (HR: 4.93, p-value = 0.0001) and T1 tumor stage (HR: 2.04, p-value = 0.0159) were associated with shorter RFS, while G3 tumor grade according to the 1973 WHO classification showed borderline significance (HR: 1.83, p-value = 0.0522). In a multivariate analysis, the two models with a concordance index exceeding 0.7 included the CD11c IDR in combination with either a history of positive re-TUR or tumor stage. We conclude that the CD11c IDR is the most informative predictor of NMIPUC recurrence after BCG immunotherapy. Our findings highlight the importance of assessment of the spatial distribution of immune cells in the tumor microenvironment.

Management of aggressive variants of papillary thyroid cancer.

PURPOSE OF REVIEW: The aim of this study was to provide a timely and relevant review of the latest findings and explore appropriate management of aggressive variants of papillary thyroid cancer (AVPTC). RECENT FINDINGS: In general, AVPTCs tend to exhibit more invasive characteristics, a lack of responsiveness to radioiodine, increased occurrences of regional spreading, distant metastases and higher mortality rates. Meanwhile, each variant showcases unique clinical and molecular profiles. SUMMARY: Given the elevated risk of recurrence postsurgery, a more aggressive strategy may be necessary when suspected preoperatively, particularly for those presenting with invasive features. Decision on the extent of surgical treatment and adjuvant therapy is individualized and made by experienced clinicians and multidisciplinary teams based on the clinical presentation, presence of aggressive features and molecular profile. Future studies on development of personalized medicine and molecular target therapy may offer tailored treatment options.

Label-free detection of invasive micropapillary carcinoma of the breast using multiphoton microscopy.

Invasive micropapillary carcinoma of the breast (IMPC) is a rare form of breast cancer with unique histological features, and is associated with high axillary lymph node metastasis and poor clinical prognosis. Thus, IMPC should be diagnosed in time to improve the treatment and management of patients. In this study, multiphoton microscopy (MPM) is used to label-free visualize the morphological features of IMPC. Our results demonstrate that MPM images are well in agreement with hematoxylin and eosin staining and epithelial membrane antigen staining, indicating MPM is comparable to traditional histological analysis in identifying the tissue structure and cell morphology. Statistical analysis shows significant differences in the circumference and area of the glandular lumen and cancer nest between the different IMPC cell clusters with complete glandular lumen morphology, and also shows difference in collagen length, width, and orientation, indicating the invasive ability of different morphologies of IMPC may be different.

Microcarcinoma papilar de tiroides: vigilancia activa. Revisión de la bibliografía / Papillary thyroid microcarcinoma: active surveillance. Literature review

El cáncer de tiroides ha aumentado en incidencia, sin embargo, la mortalidad se mantiene estable. Muchas de estas lesiones son a expensas de un microcarcinoma papilar de tiroides definido por la OMS como aquel carcinoma papilar de tiroides que en su diámetro máximo no sobrepasa los 10 mm. El avance de la imagenología sobre todo la ecografía de alta resolución y el hallazgo en pieza de anatomía patológica por lesiones benignas son las principales causas del aumento en el diagnóstico de esta entidad. La vigilancia activa surge entonces como alternativa de manejo para pacientes portadores de microcarcinoma papilar con bajo riesgo de progresión, obteniendo resultados oncológicos comparables. Independiente de su tratamiento el pronóstico de estos pacientes es excelente con sobrevida cercana al 100% en 10 años. A pesar de lo dicho la morbilidad de las distintas opciones terapéuticas es muy distinta. Será fundamental buscar elementos clínicos y paraclínicos que permitan tomar una decisión práctica, con el fin de determinar qué pacientes con microcarcinomas papilares que podrán entrar en un protocolo de vigilancia activa. Esta revisión pretende examinar la bibliografía publicada al respecto como alternativa de manejo, y su eventual aplicación en Uruguay.

Thyroid cancer has increased in incidence; however, mortality remains stable. Many of these lesions are at the expense of papillary thyroid microcarcinoma defined by the WHO as papillary thyroid carcinoma that in its maximum diameter does not exceed 10 mm. The advance of imaging, especially high-resolution ultrasound and the finding of benign lesions in pathological anatomy specimens are the main causes of the increase in the diagnosis of this entity. Active surveillance arises then as a management alternative for patients with papillary microcarcinoma with low risk of progression, obtaining comparable oncologic results. Regardless of their treatment, the prognosis of these patients is excellent with a survival rate close to 100% in 10 years. In spite of what has been said, the morbidity of the different therapeutic options is very different. It will be essential to look for clinical and paraclinical elements that will allow making a practical decision, in order to determine which patients with papillary microcarcinomas will be able to enter an active surveillance protocol. This review aims to examine the literature published on this subject as a management alternative, and its eventual application in Uruguay.

Analysis of Prognostic Factors and Construction of Prognostic Models for Invasive Micropapillary Carcinoma of the Breast.

Objective: To compare and analyze the clinical characteristics of invasive micropapillary carcinoma (IMPC) of the breast (IMPC-B) and invasive ductal carcinoma (IDC) of the breast (IDC-B) and establish a prognostic model of IMPC-B. Methods: We retrospectively analyzed data for patients diagnosed with breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018 and screened 581 patients with IMPC and 1325 patients with IDC. We compared age, race, laterality, tumor site, histological grade, type of surgery, radiation, chemotherapy, whether the first primary tumor, T stage, N stage, M stage, and molecular type between IMPC-B and IDC-B and draw survival curves of IMPC-B and IDC-B. The relationship between clinical factors and prognosis was investigated by univariate analysis using the Log-rank test and multivariate analysis of the Cox proportional hazards regression model. A risk scoring model was constructed based on independent risk factors to distinguish high-risk and low-risk patients; in addition, a nomogram was created to predict patient survival. Results: There were differences between the two groups in the age of onset, race, tumor site, histological grade, type of surgery, N stage, and molecular type (p < 0.05). Overall survival was decreased in IMPC-B compared with IDC-B (p < 0.05). The prognosis of IMPC-B was significantly correlated with histological grade, whether the first primary tumor, type of surgery, radiotherapy, chemotherapy, T stage, and N stage. Based on the relationship between the above factors and overall survival prognosis, the risk score model we constructed can effectively distinguish high-risk and low-risk patients (p < 0.05). The established nomogram had better performance in predicting survival in patients with IMPC-B (C - index = 0.78). Conclusion: IMPC-B has a worse prognosis than IDC-B, with earlier age of onset, higher histological grade, and later N stage, and luminal breast cancer is the main type. The nomogram can well predict the prognosis of patients with IMPC-B, which has a high clinical reference value and provides a scientific basis for clinical treatment.

Bibliometric insights in advances of papillary thyroid microcarcinoma: Research situation, hot points, and global trends.

Background: Thyroid cancer has been on the rise over the last decade. Papillary thyroid microcarcinoma (PTMC) accounts for more than half of all thyroid cancers. Micropapillary carcinoma of the thyroid is a common but non-fatal form of thyroid cancer. To better comprehend, nearly two decades of scientific outputs were analyzed and summarized using bibliometric methods in this study. Methods: Approximately 1098 publications from 2000 and 2021 were included in WoS database through systematic retrieval. The general information was characterized, and developmental skeleton and research frontiers were explored. CiteSpace, VOSviewer, and R, Tableau were used to evaluate and visualize the results. Results: A total of 1098 publications from across 75 countries were identified. The annual number of publications showed an increasing trend in the past 21 years. China, Korea, the United States of America (USA), Italy, and Japan made remarkable contributions to the research of PTMC. Thyroid was the most productive journal. Miyauchi Akira published maximum articles. The utmost productive institution was the University of Ulsan. Risk stratification, active surveillance, and thermal ablation garnered the attention of researchers leading to novel approaches in the clinical diagnosis and treatment of micropapillary thyroid carcinoma. Conclusions: This bibliometric study provides a comprehensive analysis of global productivity, collaboration, and research hotspots within PTMC field, which will aid in directing research toward PTMC in the coming years.

Clinical-Pathological Features and Treatment Outcome of Patients With Hobnail Variant Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) with hobnail areas above 30% is classified as hobnail variant (HVPTC). Although it is widely accepted that HVPTC has a worse outcome than classical PTC, it is unclear whether PTC with hobnail features below 30% is as aggressive as HVPTC. We gathered the largest mono-institutional series of PTC with hobnail areas and HVPTC to evaluate differences in terms of pathological features of aggressiveness, molecular profile, and treatment outcome. A total of 99 PTC with hobnail features above 5% were retrospectively selected; 34 of them met the criteria for HVPTC (0.4% of all PTC diagnosed at our institution). All tumors showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery. Structural persistence was significantly more common in patients with HVPTC (37.5% vs. 8.7%), while no differences were observed considering structural and biochemical persistence together. The presence of hobnail features identifies locally aggressive tumors, and, consequently, it should be always acknowledged in the pathological report. However, tumors with more than 30% hobnail areas frequently present TERT promoter mutations, advanced disease stage, and structural persistence after radioiodine ablation.

Can Active Surveillance Management be Developed for Patients With Low-Risk Papillary Thyroid Microcarcinoma? A Preliminary Investigation in a Chinese Population.

OBJECTIVE: Active surveillance (AS) has been shown to be a safe approach that can effectively block transition from overdiagnosis to overtreatment in patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to determine whether the AS approach can be implemented in China and investigate the population characteristics of Chinese patients who underwent AS. METHODS: The epidemiologic and clinical characteristics as well as patient adherence were evaluated in 115 patients who underwent AS management as an alternative to immediate surgery for low-risk (or highly suspected) PTMC. RESULTS: The mean patient age was 41.8 ± 10.3 years, with 41.7% and 4.4% of the patients aged <40 and ≥60 years, respectively. The median baseline diameter of index tumors was 4 (range, 3-6) mm, with 73.0% of the tumors being ≤5 mm. A total of 84.4% of the patients had a junior college, college, or graduate degree, and 83.5% were employed by the government, public institutions, companies, or technical posts. After a median 25-month follow-up, a tumor growth of ≥3 mm occurred in 3 patients (2.6%), and no new lymph node metastasis occurred. Surgery was performed in 4 patients because of patient preferences rather than because of disease progression. There was satisfactory adherence in 109 patients (94.8%) in a simulated ideal medical environment. CONCLUSION: The AS approach can be used as an alternative to low-risk PTMC management in China. Given the difference in epidemiologic and clinical characteristics, Chinese institutions should fully consider the features of the Chinese population while developing candidate criteria, surveillance intervals, and follow-up strategies for AS.

Forty-eight-year-old female MUTYH carrier presenting with five concurrent primary cancers.

BACKGROUND: MUTYH-associated polyposis is a rare disorder resulting from mutations involved in DNA mismatch repair. This results in an increased susceptibility to colonic adenomatosis and other cancers. Studies have examined the resulting frequency of extracolonic manifestations; however, these typically occur alone, concurrently, or temporally separate from an already diagnosed colorectal cancer in individuals with a biallelic mutation. CASE: Reported here is a case of five distinct primary neoplasms presenting simultaneously in a patient monoallelic for an MYH mutation. These neoplasms included squamous cell carcinoma of the vulva, rectal adenocarcinoma, synchronous anal adenocarcinoma, papillary thyroid carcinoma, and ovarian serous psammocarcinoma. Throughout her course, she underwent multiple surgical procedures, neoadjuvant chemoradiation, with further adjuvant therapy, and treatment ongoing. Due to her unique presentation, she underwent genetic testing that demonstrated she was monoallelic for an MYH mutation. CONCLUSION: The patient had a positive response to her treatment and surgical procedures with ongoing adjuvant therapy. She will continue to undergo further genetic testing, and testing for her children is being considered. This case demonstrates a unique presentation associated with a monoallelic MYH mutation that is not described in the current literature and warrants further investigation.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

Optimization of follow-up in patients with papillary thyroid cancer who show no evidence of disease 9-12 months after treatment.

BACKGROUND: Papillary thyroid cancer (PTC) has an excellent prognosis, and recurrence is rare in patients with no evidence of disease (NED) after initial treatment. Despite this, several guidelines recommend long and costly follow-up, with limited evidence of improved patient outcomes. This study aims to examine the value of follow-up in patients with NED after treatment for PTC, by determining the rate of recurrence, recurrence-associated morbidity, and death, and whether any recurrence was diagnosed through the follow-up programme. METHODS: Patients operated for PTC at Lund University Hospital between January 2004 and December 2016 were eligible. Patients with T1a N0/NX were excluded as well as patients with any other thyroid malignancy. Data were collected retrospectively by searching the patients' medical records. NED was defined as thyroglobulin less than 1 ng/ml, thyroglobulin antibodies less than 20 kIU/l, and negative imaging. Biochemical recurrence was defined as thyroglobulin greater than 1 ng/ml, and/or thyroglobulin antibodies greater than 20 kIU/l. Structural recurrence was defined as a strong suspicion of recurrence on imaging and/or histological proof of recurrence. RESULTS: Out of a cohort of 187 patients, there were 90 patients with NED who were followed for a median of 6.3 years. Three patients had biochemical recurrence; none of them had symptoms, nor were they treated for their recurrence. Three had structural recurrence; all were above 75 years old and only one was diagnosed through the follow-up programme. No patient died of PTC; five patients died during the follow-up. CONCLUSION: Follow-up as it is designed today cannot identify recurrences accurately and seems to be of questionable benefit in younger patients with NED after treatment for PTC.

Pregnancy exacerbated lymph node metastasis of well differentiated thyroid carcinoma: A case report.

INTRODUCTION: Differentiated thyroid carcinoma is the second most frequently diagnosed cancer during pregnancy, second to breast cancer. Pregnancy can cause an increase in the size of existing thyroid nodules due to the similar structure of placental human chorionic gonadotropin and thyroid stimulating hormone. However, the impact of pregnancy on malignant thyroid tumors is still unclear. PATIENT CONCERNS: We report a 27-year-old woman with initial thyroid follicular carcinoma was managed with total thyroidectomy and radioiodine therapy. Tumor recurrences with right neck lymph node enlargement were noted during the first and third trimester of pregnancy two years after initial diagnosis. DIAGNOSIS: Right neck lymph node dissection was performed for two episodes of recurrence and the pathology revealed both metastatic papillary thyroid carcinoma, follicular variant but with different pathologic features. And next-generation DNA sequencing of 275 cancer-related genes, which was a commercial set, including common mutations in thyroid cancer revealed only point mutations with unknown clinical correlation. INTERVENTION: For the first recurrence during pregnancy, right neck lymph node dissection was performed at the second trimester of pregnancy. As for the second recurrence in the third trimester of pregnancy, the patient received right neck lymph node dissection with radioiodine therapy one month after uncomplicated delivery. OUTCOMES: After complete treatment with surgery and radioiodine therapy, the serum thyroglobulin level was 10 ng/ml. During two-year regular follow-ups with serum thyroglobulin and ultrasound, no more recurrence was noted. CONCLUSION: Pregnancy in differentiated thyroid cancer survivors should be managed and monitored with caution, especially when cancer recurrence is noticed. Further studies are recommended to investigate these previously unreported gene mutations associated with thyroid cancer.

Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma.

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) has been accepted worldwide as safe and effective. Despite the growing acceptance of AS in the management of low-risk PTMCs, there are barriers to AS in real clinical settings, and it is important to understand and establish appropriate AS protocol from initial evaluation to follow-up. PTMC management strategies should be decided upon after careful consideration of patient and tumor characteristics by a multidisciplinary team of thyroid cancer specialists. Patients should understand the risks and benefits of AS, participate in decision-making and follow structured monitoring strategies. In this review, we discuss clinical outcomes of AS from previous studies, optimal indications and follow-up strategies for AS, and unresolved questions about AS.

Clinical Relevance and Management of Recurrent Laryngeal Nerve Inlet Zone Lymph Nodes Metastasis in Papillary Thyroid Cancer.

Background: Recurrent nodal disease often occurs in recurrent laryngeal nerve inlet zone (RLNIZ), leading to difficult surgical management. Methods: Medical records of 947 patients with PTC and 33 patients with recurrent PTC were retrospectively reviewed. Totally 169 sides of RLNIZ dissection in 152 patients (17 cases were bilateral and 135 cases were unilateral) with primary surgery and 4 patients with structural recurrent disease were included for the analysis. Results: The rate of lymph node metastasis in RLNIZ was 31.3% (47/150). The incidence of transient hypoparathyroidism was 5.9% and no RLN injury and permanent hypoparathyroidism occurred. RLNIZ lymph nodes metastasis (LNM) was significantly associated with age <45 years, larger tumor size, number of CNLNM, and lateral node metastasis. CNLNM and lateral node metastasis were independent risk factors for RLNIZ LNM. Recurrent nodal disease in RLNIZ was identified in four of 33 patients and permanent recurrent laryngeal nerve (RLN) injury was observed in one of four patients. Conclusion: Lymph nodes in RLNIZ are usually involved in patients with heavy tumor burden and can be removed safely at initial surgery. Once central or lateral LNM was confirmed preoperatively or intraoperatively, RLNIZ lymph node dissection should be carefully performed to reduce the rate of structural recurrence in the central compartment.

Urothelial carcinoma of the graft kidney with molecular analyses: a rare case report.

BACKGROUND: Malignancy after transplantation is a leading cause of death among kidney transplant recipients. However, donor-derived malignancies are rare. We report a case of a high grade papillary urothelial carcinoma arising in a transplanted kidney. CASE PRESENTATION: A 62-year-old female who received a kidney transplantation more than 30 years ago presented with urinary tract infection, acute renal failure, and hydronephrosis of the transplant kidney. Anterograde nephrostogram showed a large filling defect in the lower pole of the transplant kidney and in the proximal 3-4 cm of the ureter. A biopsy from the renal pelvic mass showed a high grade urothelial carcinoma. She underwent an anterior exenteration, resection of both transplant and native kidneys and bilateral pelvic lymph node dissection. Pathologic examination showed a high grade papillary urothelial carcinoma which appeared to arise in the pelvis of the graft kidney, involve the graft ureter and native urinary bladder. The tumor had metastasized to one left obturator lymph node but spared the two native kidneys and ureters. Short tandem repeat (STR) analysis confirmed the tumor to be of donor origin. Next-generation sequencing identified amplification of TERT and loss of CDKN2A/CDKN2B in the primary tumor. CONCLUSION: While it is known that transplant recipients have an increased risk of urothelial carcinoma compared to the general population, the lack of the well-documented risk factors, such as older age at transplantation, BK polyomavirus infection, and prolonged post-transplantation history and dissemination of the tumor in this case shed light on the de novo tumorigenesis of the graft kidney within the host microenvironment. Amplification of Telomerase reverse transcriptase (TERT) and loss of cyclin dependent kinase inhibitor 2A/2B (CDKN2A/CDKN2B) detected in the tumor by next gene sequencing suggests that they may play an important role in this case.

Presence of TERT ± BRAF V600E mutation is not a risk factor for the clinical management of patients with papillary thyroid microcarcinoma.

BACKGROUND: The management of papillary thyroid microcarcinomas with TERT ± BRAF V600E mutations remains controversial owing to their potential associations with tumor aggressiveness. This study evaluated the clinical implications of these mutations in management of patients with papillary thyroid microcarcinomas. METHODS: Between June 2019 and October 2020, surgical specimens from 504 consecutive patients with papillary thyroid microcarcinomas were obtained at a tertiary hospital. The mutation statuses of TERT promoter and BRAF V600E were assessed by polymerase chain reaction. The prevalence and relationships of TERT ± BRAF V600E mutations with clinical, radiological, and pathological characteristics were evaluated. RESULTS: Of 504 patients with papillary thyroid microcarcinomas, TERT ± BRAF V600E mutations were found in 3.2% (16/504). Of these 16 patients, 93.8% (15/16) of papillary thyroid microcarcinomas with TERT promoter mutations also harbored BRAF V600E mutations. Correlation analysis showed that TERT ± BRAF V600E mutations were not associated with aggressive clinical, radiological, or pathological features (P > .05). The presence of lymph node metastasis was not associated with mutation status (P = .834). CONCLUSION: TERT ± BRAF V600E mutations in patients with papillary thyroid microcarcinomas are not associated with any unfavorable clinicopathological features, including lymph node metastasis status.

Papillary thyroid microcarcinomas: does subtyping predict aggressive clinical behavior?

The most common malignant neoplasm affecting the thyroid gland is papillary thyroid carcinoma (PTC). PTC can demonstrate a number of morphologic variants including, but not limited to, classic, follicular, and tall cell. Each of these morphologic subtypes carry distinct clinical characteristics such that certain variants, like tall cell, behave more aggressively than others. PTCs measuring less than or equal to 1.0 cm are classified as microcarcinomas. Although these lesions are thought to be clinically indolent, we hypothesized that, like their larger counterparts, certain histologic variants may lead to worse patient outcomes. To test our hypothesis, we analyzed our pathology archives between the years 2009 and 2020 for papillary thyroid microcarcinomas and assessed whether different morphologic features correlated with more aggressive clinical behavior. Our findings suggest that certain variants exhibit features that portend a more worrisome clinical course and thus papillary thyroid microcarcinomas should be subtyped to help predict patient outcome.

Psychological Distress and Sleep Disturbance Throughout Thyroid Nodule Screening, Diagnosis, and Treatment.

CONTEXT: Many controversies exist regarding screening and treatment of thyroid cancer (TC), especially papillary thyroid microcarcinoma (PTMC). OBJECTIVE: The aim of this study was to evaluate patients' psychological distress and sleep disturbance throughout thyroid nodule (TN) screening, diagnosis, and treatment. METHODS: A total of 2834 participants (1153 participants with TNs) were enrolled during the screening phase, and 1105 individuals with TNs (87 individuals with TC) were enrolled during the diagnosis phase. Of the 87 TC patients, 66 underwent immediate operation (OP), and 21 patients with PTMC opted for active surveillance (AS). Four validated scales were applied to quantify the outcome indicators at prescreening, postscreening, postdiagnosis, and posttreatment. RESULTS: Higher psychological distress and sleep disturbance were found postscreening than prescreening in subjects with TNs, but no differences in those without nodules. Compared with postscreening, higher scores of psychological distress and sleep disturbance were identified in patients with suspicious TC treated with fine needle aspiration (FNA) or with AS. Lower psychological distress and sleep disturbance were noted for patients with benign nodules than for TC patients. OP for TC, especially PTMC, did not alleviate psychological distress or sleep disturbance compared with the same parameters in patients who underwent AS. CONCLUSION: Based on the findings of impaired psychological health and sleep quality, screening for TNs in adults who show no symptoms should be performed with caution. Psychological distress and sleep disturbance should also be taken into consideration when FNA is performed for suspected TC or OP for papillary thyroid cancer, especially PTMC.