Noninvasive Papillary Urothelial Carcinoma of the Bladder: An Institutional Experience Focusing on Tumors With Borderline Features.

CONTEXT.­: Noninvasive papillary urothelial carcinomas (PUCs) comprise most urinary bladder tumors. Distinction between low-grade (LG-PUC) and high-grade (HG-PUC) PUCs is pivotal for determining prognosis and subsequent treatment. OBJECTIVE.­: To investigate the histologic characteristics of tumors with borderline features between LG-PUC and HG-PUC, focusing on the risk of recurrence and progression. DESIGN.­: We reviewed the clinicopathologic parameters of noninvasive PUC. Tumors with borderline features were subcategorized as follows: tumors that look like LG-PUC but have occasional pleomorphic nuclei (1-BORD-NUP) or elevated mitotic count (2-BORD-MIT), and tumors with side-by-side distinct LG-PUC and less than 50% HG-PUC (3-BORD-MIXED). Recurrence-free, total progression-free, and specific invasion-free survival curves were derived from the Kaplan-Meier method, and Cox regression analysis was performed. RESULTS.­: A total of 138 patients with noninvasive PUC were included, with the following distribution: LG-PUC (n = 52; 38%), HG-PUC (n = 34; 25%), BORD-NUP (n = 21; 15%), BORD-MIT (n = 14; 10%), and BORD-MIXED (n = 17; 12%). Median (interquartile range) follow-up was 44.2 months (29.9-73.1 months). Invasion-free survival was different between the 5 groups (P = .004), and pairwise comparison showed that HG-PUC had a worse prognosis compared with LG-PUC (P ≤ .001). On univariate Cox analysis, HG-PUC and BORD-NUP were 10.5 times (95% CI, 2.3-48.3; P = .003) and 5.9 times (95% CI, 1.1-31.9; P = .04) more likely to invade, respectively, when compared to LG-PUC. CONCLUSIONS.­: Our findings confirm a continuous spectrum of histologic changes in PUC. Approximately a third of noninvasive PUCs show borderline features between LG-PUC and HG-PUC. Compared with LG-PUC, BORD-NUP and HG-PUC were more likely to invade on follow-up. BORD-MIXED tumors did not statistically behave differently from LG-PUC.

The efficacy of a pilot pediatric cognitive remediation summer program to prepare for transition of care.

This study assessed the efficacy of a time-sensitive cognitive remediation summer program (CRSP) that provided patients and their families with tools to help mitigate neurocognitive deficits and promote independence to foster precursor transition of medical care skills. A total of 38 participants (aged 9-15) were included in one of the CRSPs offered yearly from 2013 to 2016. A longitudinal design was employed and at each evaluation time point, one week before start of the CRSP (pre-testing) and within three weeks after the end of the program (post-testing)), participants were administered measures of executive functioning in addition to parent ratings of behavior, executive functioning, and adaptive skills (Year 1-Year 4). In Year 4, additional measures were collected, including parenting style and parent engagement and involvement in the program. Results from Year 1 to Year 4 (n = 35) demonstrated that participants in the CRSP showed significant improvement on neuropsychological testing in sustained and selective attention, planning, and cognitive flexibility. Robust changes in parent ratings of adaptive functioning from pre- to post-treatment were also found. Specific to Year 4 (n = 13), results revealed that participants showed improvement in levels of independence with at least one of the individualized goals focused on during the program. This study provided a systematic method to gauge the levels of instruction necessary to reach goals, a crucial tool in skill-teaching. Overall, our study provides evidence for the efficacy of the CRSP and validates a feasible intervention that can be integrated into standard of care for pediatric medical populations.

Tracking of neurocognitive outcomes over time in children with perinatal stroke and associated complex medical conditions: a case series.

Neurocognitive outcomes in children with perinatal stroke are complicated by additional neurological/medical factors. The main objective of this study was to retrospectively examine long-term neurocognitive outcomes in five children with perinatal stroke with increasingly complex comorbidities; ages 5-7 at first evaluation. Results revealed that intelligence and academic skills were significantly decreased in cases with combined perinatal stroke and comorbidities. Early language development was particularly vulnerable to disruption over time in children with increasing medical complexity. The delayed emergence of neurocognitive deficits emphasizes the need for serial assessment of neurocognitive development to identify early services and interventions.

Management of benign middle ear tumors: A series of 7 cases.

Benign middle ear tumors represent a rare group of neoplasms that vary widely in their pathology, anatomy, and clinical findings. These factors have made it difficult to establish guidelines for the resection of such tumors. Here we present 7 unique cases of these rare and diverse tumors and draw from our experience to recommend optimal surgical management. Based on our experience, a postauricular incision is necessary in nearly all cases. Mastoidectomy is required for tumors that extend into the mastoid cavity. Whenever exposure or hemostasis is believed to be inadequate with simple mastoidectomy, canal-wall-down mastoidectomy should be performed. Finally, disarticulation of the ossicular chain greatly facilitates tumor excision and should be performed early in the procedure.

Nonneoplastic lesions of the prostate and bladder.

CONTEXT: Specimens from the prostate and bladder are commonly encountered by the general surgical pathologist. Emphasis is usually placed on neoplasms of the bladder and prostate, particularly if malignant, owing to their therapeutic consequences. A good command of benign lesions occurring in the bladder and prostate, and knowledge of their preneoplastic potential will help pathologists confidently diagnose malignancy versus its benign mimickers and guide the urologists in choosing the appropriate therapy and follow-up for the patient. OBJECTIVE: To present a mixture of benign entities, and discuss their histologic and clinical characteristics, hoping to provide a practical review for the general surgical pathologist. DATA SOURCES: An extensive review of the literature on the entities discussed was performed. CONCLUSIONS: A wide variety of benign entities are present in the prostate and bladder. Benign lesions in the prostate can be age related, such as prostatic atrophy and benign prostatic hyperplasia; transition zone associated, such as basal cell hyperplasia, adenosis, and sclerosing adenosis; or prostatic urethra associated. Benign lesions of the bladder encompass a wide variety of reactive changes that can occur in the urothelium, as well as hyperplastic lesions or reactive proliferations that could be misdiagnosed as malignant. The bladder responds to chronic irritation through several reactive/metaplastic lesions such as cystitis cystica/glandularis, keratinizing squamous metaplasia, or nephrogenic metaplasia. The urothelium can also give rise to hyperplastic/proliferative lesions, in particular von Brunn nest hyperplasia, papillary polypoid cystitis, and pseudocarcinomatous proliferation, which should be distinguished from malignant processes. Ectopic tissue, such as prostatic or mullerian, can also be seen.

Parental distress, parenting practices, and child adaptive outcomes following traumatic brain injury.

Moderate and severe pediatric traumatic brain injuries (TBI) are associated with significant familial distress and child adaptive sequelae. Our aim was to examine the relationship between parental psychological distress, parenting practices (authoritarian, permissive, authoritative), and child adaptive functioning 12-36 months following TBI or orthopedic injury (OI). Injury type was hypothesized to moderate the relationship between parental distress and child adaptive functioning, demonstrating a significantly stronger relationship in the TBI relative to OI group. Authoritarian parenting practices were hypothesized to mediate relationship between parental distress and child adaptive functioning across groups. Groups (TBI n = 21, OI n = 23) did not differ significantly on age at injury, time since injury, sex, race, or SES. Parents completed the Brief Symptom Inventory, Parenting Practices Questionnaire, and Vineland-II. Moderation and mediation hypotheses were tested using hierarchical multiple regression and a bootstrapping approach, respectively. Results supported moderation and revealed that higher parental psychological distress was associated with lower child adaptive functioning in the TBI group only. Mediation results indicated that higher parental distress was associated with authoritarian parenting practices and lower adaptive functioning across groups. Results suggest that parenting practices are an important area of focus for studies attempting to elucidate the relationship between parent and child functioning following TBI.

Establishing a pediatric cognitive rehabilitation program: insurance issues and clinical rationale.

Technological and medical advances have greatly improved survival rates for many disorders; therefore, more attention is being given to functional outcomes in individuals who have been diagnosed with neurological diseases or disorders. One example of such an endeavor consists of a cognitive rehabilitation program to improve attentional abilities. The current study uses a modification of the original Cognitive Remediation Program to address attentional deficits in children with a variety of neurological disorders. The abbreviated program is designed as a focused, time-limited program that can be easily implemented in inpatient, partial day, or outpatient medical settings using third party payment to fund the program. This article seeks to inform psychologists about how to establish a cognitive rehabilitation program with emphasis placed on providing information about insurance reimbursement and billing procedures. Information is presented regarding billing codes, materials required for reimbursement, the denial/approval process, and percent of the Usual Customary Reasonable charge that was covered. Recommendations to improve the timeliness and efficiency of the reimbursement process, as well as to increase the amount of reimbursement, are highlighted. Directions for future research, including continued documentation of the effectiveness of cognitive rehabilitation programs to establish credibility for procurement of third party payment, are also offered.

Nonischemic laparoscopic partial nephrectomy using a novel wet monopolar device in a porcine model.

BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) is the minimally invasive standard of care for the management of a cT(1a) renal mass. We evaluated a novel saline enhanced electrosurgical resection (SEER) device for performance of a nonischemic LPN. MATERIALS AND METHODS: Six pigs were used in a nonsurvival pilot study. Energy penetration was characterized by applying the SEER to the lower pole of each kidney for 30 seconds, 1 minute, and 3 minutes using pure cutting energy at 100W and a drip rate of 1 drip per second. Energy testing was performed with the hilum clamped in six kidneys and without clamping in six kidneys. Subsequently, a nonischemic upper pole LPN was performed with the SEER device, and the kidneys were harvested. The areas of necrosis were sectioned and stained with hematoxylin and eosin. Depth of necrosis was visualized grossly and microscopically for each time point. We also recorded time to perform LPN, estimated blood loss (EBL), and subjective severity of bleeding. RESULTS: The average operative time was 15.4 minutes. The mean EBL was 44.2 mL with nine (75%) cases classified as minimal, 2 (17%) moderate, and 1 (8%) severe bleeding. The mean depth of necrosis on the kidney remnants was 2.97 mm. The mean depth of necrosis for unclamped kidneys at 30 seconds, 1 minute, and 3 minutes was 0.38 mm, 0.88 mm, and 1.27 mm, respectively. The mean depths for the clamped kidneys were 2.73 mm, 3.23 mm, and 8.68 mm respectively. Depth of necrosis was significantly higher in the clamped kidneys at 3 minutes (P=0.0035). CONCLUSIONS: In the porcine model, the SEER transected parenchyma and collecting system with low resection times and minimal blood loss. Use of coagulation during resection is the main advantage of a monopolar resection compared with cold scissors. Testing performed for 3 minutes during hilar clamping demonstrated a significantly deeper level of necrosis.

Inhibition of cyclo-oxygenase 2 reduces tumor metastasis and inflammatory signaling during blockade of vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) blockade is an effective therapy for human cancer, yet virtually all neoplasms resume primary tumor growth or metastasize during therapy. Mechanisms of progression have been proposed to include genes that control vascular remodeling and are elicited by hypoperfusion, such as the inducible enzyme cyclooxygenase-2 (COX-2). We have previously shown that COX-2 inhibition by the celecoxib analog SC236 attenuates perivascular stromal cell recruitment and tumor growth. We therefore examined the effect of combined SC236 and VEGF blockade, using the metastasizing orthotopic SKNEP1 model of pediatric cancer. Combined treatment perturbed tumor vessel remodeling and macrophage recruitment, but did not further limit primary tumor growth as compared to VEGF blockade alone. However, combining SC236 and VEGF inhibition significantly reduced the incidence of lung metastasis, suggesting a distinct effect on prometastatic mechanisms. We found that SC236 limited tumor cell viability and migration in vitro, with effects enhanced by hypoxia, but did not change tumor proliferation or matrix metalloproteinase expression in vivo. Gene set expression analysis (GSEA) indicated that the addition of SC236 to VEGF inhibition significantly reduced expression of gene sets linked to macrophage mobilization. Perivascular recruitment of macrophages induced by VEGF blockade was disrupted in tumors treated with combined VEGF- and COX-2-inhibition. Collectively, these findings suggest that during VEGF blockade COX-2 may restrict metastasis by limiting both prometastatic behaviors in individual tumor cells and mobilization of macrophages to the tumor vasculature.

PAX8 and PAX2 immunostaining facilitates the diagnosis of primary epithelial neoplasms of the male genital tract.

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.

A pilot study evaluating an abbreviated version of the cognitive remediation programme for youth with neurocognitive deficits.

PRIMARY OBJECTIVE: To determine the effectiveness of an abbreviated version of an established cognitive remediation programme for children with neurological disorders and attention problems in an outpatient setting. METHODS AND PROCEDURES: Eighteen 6-15-year-old children diagnosed with neurological and attention difficulties completed a six-module training programme aimed at improving attention. This programme was a shorter version of the Cognitive Remediation Programme (CRP), which has been successfully implemented with children with neurocognitive deficits. Parents completed measures of their children's attention and children completed neuropsychological measures of attention. MAIN OUTCOMES AND RESULTS: The programme was associated with improvement in several aspects of parent-reported attention and children's performance on tasks measuring attention. CONCLUSIONS: The shortened version of the CRP shows promise as a brief treatment for attention problems in outpatient neurological populations. Future research should assess programme effectiveness using a control group, longer-term follow-up and teacher reports.

Comparison of two core biopsy techniques before and after laparoscopic cryoablation of small renal cortical neoplasms.

INTRODUCTION: Cryoablation is an acceptable treatment option for small renal cortical neoplasms (RCN). Unlike extirpative interventions, intraoperative needle biopsy is the only pathologic data for ablated tumors. It is imperative that sampled tissue accurately captures pathology. We studied the optimal intraoperative needle core biopsy protocol for small RCN during laparoscopic renal cryoablation (LCA). METHODS: Patients with RCN<4cm underwent intraoperative biopsy during LCA. Four biopsy cores were taken per tumor, 2 before and 2 after LCA by using both a standard and modified technique. Standard technique: needle biopsy device was deployed after insertion into the renal tissue at a depth of 5mm. Modified technique: needle biopsy device was deployed 1mm outside of the renal tissue. Biopsies were examined and compared with reference standard pathology. Percentage agreement was calculated across biopsy types (standard vs. modified) and time points (pre- vs. postcryoablation). Logistic regression was used to identify factors impacting biopsy accuracy. RESULTS: Thirty patients with 33 RCNs underwent LCA. The mean patient age was 69.1±8.0yrs, and mean tumor size was 2.3±0.7cm. No significant bleeding resulted from biopsies. A definitive diagnosis was made in 31/33 RCNs (94.0%). Ten tumors (30.3%) were benign, 21 (63.7%) were malignant, and 2 (6.0%) were nondiagnostic. Biopsy length was significantly longer using the standard vs. modified technique with mean lengths of 9.3mm vs. 7.0mm, respectively (P=.02). Highest agreement was seen in preablation biopsies (90.3%). A significant association with agreement was seen for younger age (P=.05) and larger tumor size (P=.02). CONCLUSIONS: Younger age and larger tumor size were associated with improved accuracy. Preoperative sampling resulted in superior accuracy and the standard technique resulted in significantly longer cores. Use of preablation standard biopsy technique may result in the most accurate pathologic diagnosis for patients undergoing cryoablation for small RCNs.

Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study.

Cell-lineage-specific transcription factors are a group of regulatory proteins expressed in embryonic, differentiated, or neoplastic cells of the same lineage and represent a valuable repertoire of tissue-specific markers for the diagnosis of human tumors. Together with PAX2, PAX8 is a nephric-lineage transcription factor and is required for the establishment of renal-lineage cells and the formation of the kidney. In contrast to PAX2, little is known about the expression of PAX8 in adult kidney and renal tumors. In this study, we used immunohistochemistry to investigate the expression of PAX8 in adult human kidney and renal epithelial tumors. We report here that PAX8 was detected in renal epithelial cells in all segments of renal tubules from the proximal tubules to the renal papillae and in the parietal cells of Bowman's capsule in the adult kidney. PAX8 was also present in 98% of clear cell renal cell carcinomas (RCCs), 90% of papillary RCCs, and 95% of oncocytomas, similar to PAX2. In addition, PAX8 was found in 82% of chromophobe RCCs, 71% of sarcomatoid components of RCCs, and 100% (2/2) of renal medullary carcinomas. Overall, PAX8 was detected in 85% of metastatic renal tumors. Interestingly, expression of PAX8 was noted in some urothelial cells in the renal pelvis and ureters and approximately 23% of urothelial carcinomas of the renal pelvis, but not in the urothelium or urothelial carcinomas of the urinary bladder; this probably underlines the different embryonic origins of urothelial cells in the upper and lower urinary tracts. As shown in this study, PAX8 is widely expressed in normal and neoplastic renal tissues. PAX8 may be a useful additional marker for renal epithelial tumors; however, its specificity and sensitivity await further investigation.

Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis?

Recent evidence has showed that nephrogenic adenoma is a true "nephrogenic" lesion derived from the proliferation of exfoliated and implanted renal tubular cells in the urinary tract, a process that closely resembles the formation of endometriosis. This new concept has led to the identification of renal transcription factor PAX2 as a diagnostic marker for nephrogenic adenoma. PAX8 is another transcription factor structurally and functionally related to PAX2. Both are cell lineage restricted transcription factors expressed in normal and neoplastic tissues of related origin, including renal tubular cells in both fetal and adult kidneys. In this study, we investigated the expression of PAX8 in nephrogenic adenoma and its mimics. We report here that PAX8 was detected in all nephrogenic adenomas (N=35) and clear cell adenocarcinoma of the lower urinary tract (N=7), but not in prostate adenocarcinoma (N=100), adenocarcinoma (N=9), squamous cell carcinoma (N=5), or urothelial carcinoma (N=48) of the urinary bladder and its variants. PAX8 was neither detected in normal urothelium of the urinary bladder nor in prostate glands and stroma. PAX2 was also detected in 2 of the 7 clear cell adenocarcinomas of the lower urinary tract. We suggest that PAX8 is an additional marker for identifying nephrogenic adenoma. Expression of PAX8 or PAX2 in both nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract may indicate a possible related tissue origin for these 2 lesions; both may be derived from proliferating renal tubular cells in the urinary tract. In addition, detection of PAX8 or PAX2 in clear cell adenocarcinoma of the lower urinary tract is helpful in differentiating it from urothelial carcinoma and its variants and adenocarcinomas of the urinary bladder or of the prostate.

Understanding the neuropsychologic outcome of pediatric AVM within a neurodevelopmental framework.

OBJECTIVE: This case series describes the long-term neuropsychologic functioning of 5 children with repaired arteriovenous malformations (AVMs). Results are presented within the context of a neurodevelopmental model to facilitate conceptualization and generate appropriate rehabilitation strategies for children with AVMs. BACKGROUND: The current case series expands upon previous research examining the long-term psychosocial functioning of these children with AVMs in which it was found that overall emotional functioning appeared adequate, although there were suggestions of defensiveness and areas of worry. In addition, global adaptive functioning was below average for most children with parental concerns about their child's socialization. METHOD: Five children with repaired AVMs in the cerebellum and frontal, temporal, and parietal lobes participated in a neuropsychologic evaluation assessing intellectual, language, memory, motor, visual-perceptual and visual-motor, and executive functions. RESULTS: These children demonstrated both localized and remote findings. More specifically, mild to moderate weaknesses in executive functions were suggested regardless of AVM location. CONCLUSIONS: The finding that children exhibited executive function difficulties regardless of AVM location is in keeping with the understanding of multiple cortical and subcortical pathways to and from the frontal lobes. In addition, it is possible that the processes of diaschisis and plasticity may play a role in the functional outcome of AVMs.

Intermediate-risk localized prostate cancer in the PSA era: radiotherapeutic alternatives.

OBJECTIVES: To retrospectively compare the biochemical disease-free survival (BDFS) of patients treated with standard dose external beam radiotherapy (SD-EBRT), SD-EBRT plus androgen deprivation (AD), and brachytherapy-based treatment (brachytherapy with or without EBRT with or without AD). METHODS: All 297 patients with intermediate-risk prostate cancer treated with these radiation-based treatments at our institution from August 1989 to June 2001 were included. Biochemical relapse was defined according to the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, a prostate-specific antigen level of 1.5 ng/mL or greater and rising on two consecutive occasions (the "Bolla" definition), and the current prostate-specific antigen nadir plus 2 ng/mL with failure dated "at call" (the "Houston/Phoenix" definition). The number of patients treated with SD-EBRT, SD-EBRT plus AD, and brachytherapy-based treatment was 141, 84, and 72, respectively. The year of treatment was analyzed as a prognostic factor. The median follow-up was 32.3, 34.7, and 41.5 months for the ASTRO, Bolla, and Houston/Phoenix definitions, respectively. RESULTS: The brachytherapy-based treatment resulted in improved BDFS compared with SD-EBRT (ASTRO definition, 5-year BDFS rate 88% +/- 5% versus 49% +/- 5%, P <0.01; Bolla definition, 88% +/- 8% versus 49% +/- 5%, P <0.01; Houston/Phoenix definition, 81% +/- 10% versus 64% +/- 5%, P = 0.01). SD-EBRT plus AD was superior to SD-EBRT alone using the Bolla definition (5-year BDFS 76% +/- 7% versus 49% +/- 5%, P <0.01) and the Houston/Phoenix definition (85% +/- 6% versus 64% +/- 5%, P = 0.01), but not using the ASTRO definition (P = 0.17). Multivariate analysis, including prostate-specific antigen, clinical stage, Gleason score, and year of treatment, demonstrated improved biochemical outcomes for brachytherapy-based treatment versus SD-EBRT (ASTRO, P <0.01; Bolla, P <0.01; and a trend toward significance with Houston/Phoenix, P = 0.07) and for the addition of AD to SD-EBRT (Bolla, P <0.01 and Houston/Phoenix, P = 0.03). The year of treatment trended toward significance (P = 0.077) on multivariate analysis using the ASTRO definition. CONCLUSIONS: For patients with intermediate-risk prostate cancer, brachytherapy-based treatment and the addition of AD to SD-EBRT resulted in improved biochemical outcomes compared with the outcomes with SD-EBRT alone; however, these findings were dependent on the definition of biochemical failure used. The year of treatment may be an important prognostic factor in intermediate-risk prostate cancer.

Fine-needle aspiration biopsy of monophasic variant of spindle epithelial tumor with thymus-like differentiation of the thyroid: report of one case and review of the literature.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare biphasic tumor of the thyroid with approximately 20 well-documented cases reported in the English literature. Although a monophasic variant of SETTLE is conceivable, the majority of the reported cases were truly biphasic tumors. A minimal amount of epithelial component was present in the reported cases of so-called spindle-cell predominant SETTLE. Here, we report an apparently monophasic case of SETTLE in a 16-yr-old girl, in which no epithelial cells were identified in either fine-needle aspiration biopsy (FNAB) or the subsequent hemithyroidectomy specimen. The FNAB smears were moderately cellular and composed of single and loosely grouped spindle cells with homogenous metachromatic material, which could be mistaken as amyloid, erroneously suggesting medullary thyroid carcinoma. The compact nodules of uniform spindle cells in histology sections raised the possibility of monophasic synovial sarcoma. The spindle cells stained positive for both cytokeratin and vimentin, but were negative for thyroglobulin and calcitonin as well as neuroendocrine markers, confirming the diagnosis of SETTLE.