Developmental arrest of Drosophila larvae elicits presynaptic depression and enables prolonged studies of neurodegeneration.

Synapses exhibit an astonishing degree of adaptive plasticity in healthy and disease states. We have investigated whether synapses also adjust to life stages imposed by novel developmental programs for which they were never molded by evolution. Under conditions in which Drosophila larvae are terminally arrested, we have characterized synaptic growth, structure and function at the neuromuscular junction (NMJ). Although wild-type larvae transition to pupae after 5 days, arrested third instar (ATI) larvae persist for 35 days, during which time NMJs exhibit extensive overgrowth in muscle size, presynaptic release sites and postsynaptic glutamate receptors. Remarkably, despite this exuberant growth, stable neurotransmission is maintained throughout the ATI lifespan through a potent homeostatic reduction in presynaptic neurotransmitter release. Arrest of the larval stage in stathmin mutants also reveals a degree of progressive instability and neurodegeneration that was not apparent during the typical larval period. Hence, an adaptive form of presynaptic depression stabilizes neurotransmission during an extended developmental period of unconstrained synaptic growth. More generally, the ATI manipulation provides a powerful system for studying neurodegeneration and plasticity across prolonged developmental timescales.

Hyperthermic intrathoracic extracorporeal chemotherapy for secondary malignant pleural disease.

OBJECTIVES: Pleural metastasis has extremely poor prognosis. Resection of pleural implants with infusion of intrathoracic hyperthermic chemotherapy may offer a survival advantage in selected patients. We evaluated the safety and efficacy of hyperthermic intrathoracic extracorporeal chemotherapy (HITEC) in patients who underwent pleurectomy/decortication (P/D) for secondary malignant pleural disease (SPD). METHODS: A total of 101 patients were evaluated over 72 months, with 35 patients electing to proceed with P/D and 60 minutes of HITEC with cisplatin at 42°C. Inclusion criteria were adults 18-79 years with unilateral pleural dissemination. Exclusion criteria were patients without control of primary site, extrathoracic metastatic disease, significant comorbidities, and a history of adverse reaction to cisplatin. RESULTS: Median age was 56 years (36-73); 60% were women. SPD was thymoma in 13, breast cancer in 9, lung cancer in 6, colon cancer in 2, renal cell in 2, and esophageal, anal, and thymic cancers in one each. There was no operative mortality. Postoperative complications occurred in 18 patients (51%). No patient developed renal failure. Median follow-up was 24 months (4-60). The overall survival rate was 61%; 17 patients (49%) developed recurrent disease at a median of 12 months (6-36). There were no recurrences after 36 months Eleven patients (31%) died of metastatic disease at a median of 17 months (7-25). CONCLUSIONS: Surgical cytoreduction of SPD followed by HITEC with cisplatin was well tolerated. No patient developed cisplatin-related toxicities. Long-term follow-up is warranted to determine survival advantage and refinement of inclusion criteria.

Protease-activated Receptor-2 (PAR-2)-mediated Nf-κB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma.

Oral cancer is the sixth most common cause of death from cancer with an estimated 400,000 deaths worldwide and a low (50%) 5-year survival rate. The most common form of oral cancer is oral squamous cell carcinoma (OSCC). OSCC is highly inflammatory and invasive, and the degree of inflammation correlates with tumor aggressiveness. The G protein-coupled receptor protease-activated receptor-2 (PAR-2) plays a key role in inflammation. PAR-2 is activated via proteolytic cleavage by trypsin-like serine proteases, including kallikrein-5 (KLK5), or by treatment with activating peptides. PAR-2 activation induces G protein-α-mediated signaling, mobilizing intracellular calcium and Nf-κB signaling, leading to the increased expression of pro-inflammatory mRNAs. Little is known, however, about PAR-2 regulation of inflammation-related microRNAs. Here, we assess PAR-2 expression and function in OSCC cell lines and tissues. Stimulation of PAR-2 activates Nf-κB signaling, resulting in RelA nuclear translocation and enhanced expression of pro-inflammatory mRNAs. Concomitantly, suppression of the anti-inflammatory tumor suppressor microRNAs let-7d, miR-23b, and miR-200c was observed following PAR-2 stimulation. Analysis of orthotopic oral tumors generated by cells with reduced KLK5 expression showed smaller, less aggressive lesions with reduced inflammatory infiltrate relative to tumors generated by KLK5-expressing control cells. Together, these data support a model wherein KLK5-mediated PAR-2 activation regulates the expression of inflammation-associated mRNAs and microRNAs, thereby modulating progression of oral tumors.

Identification of a human papillomavirus-associated oncogenic miRNA panel in human oropharyngeal squamous cell carcinoma validated by bioinformatics analysis of the Cancer Genome Atlas.

High-risk human papillomavirus (HPV) is a causative agent for an increasing subset of oropharyngeal squamous cell carcinomas (OPSCCs), and current evidence supports these tumors as having identifiable risk factors and improved response to therapy. However, the biochemical and molecular alterations underlying the pathobiology of HPV-associated OPSCC (designated HPV(+) OPSCC) remain unclear. Herein, we profile miRNA expression patterns in HPV(+) OPSCC to provide a more detailed understanding of pathologic molecular events and to identify biomarkers that may have applicability for early diagnosis, improved staging, and prognostic stratification. Differentially expressed miRNAs were identified in RNA isolated from an initial clinical cohort of HPV(+/-) OPSCC tumors by quantitative PCR-based miRNA profiling. This oncogenic miRNA panel was validated using miRNA sequencing and clinical data from The Cancer Genome Atlas and miRNA in situ hybridization. The HPV-associated oncogenic miRNA panel has potential utility in diagnosis and disease stratification and in mechanistic elucidation of molecular factors that contribute to OPSCC development, progression, and differential response to therapy.

Rotator Cuff Tears Are Related to the Side Sleeping Position.

Purpose: To determine whether there was a relationship between sleep position and symptomatic partial- and full-thickness rotator cuff tears. Methods: A consecutive series of patients that met the inclusion/exclusion criteria (n = 58) were in seen in clinic between July 2019 and December 2019. All of these individuals had a significant partial-thickness (> 50%) or full-thickness rotator cuff tear determined by either ultrasound, magnetic resonance imaging, or both. All patients in this series either had an insidious onset of shoulder pain or their symptoms were related to the basic wear and tear of daily activities. Traumatic rotator cuff tears (those associated with a significant traumatic event such as shoulder instability, motor vehicle accidents, sports related injuries, etc.) were excluded. Previous shoulder surgery, recurrent rotator cuff tears, and worker's compensation cases also were excluded from this series. As part of the history-taking process, the patients were asked what was their preferred sleeping position-side sleeper, back sleeper, or stomach sleeper. A χ2 test was conducted to determine the relationship between rotator cuff pathology and sleep position. Results: Of the 58 subjects, 52 of the patients were side sleepers, 4 were stomach sleepers, 1 was a back sleeper, and 1 preferred all 3 positions. Statistical analysis, using the χ2 test (P < .0001), demonstrated that rotator cuff tears were most often seen in side sleepers. Conclusions: In our study, there appeared to be a relationship between the preference of being a side sleeper and the presence of a rotator cuff tear. Level of Evidence: Level IV, prognostic case series.

Analysis of synaptic growth and function in Drosophila with an extended larval stage.

The Drosophila larval neuromuscular junction (NMJ) is a powerful system for the genetic and molecular analysis of neuronal excitability, synaptic transmission, and synaptic development. However, its use for studying age-dependent processes, such as maintenance of neuronal viability and synaptic stability, are temporally limited by the onset of pupariation and metamorphosis. Here we characterize larval NMJ growth, growth regulation, structure, and function in a developmental variant with an extended third instar (ETI). RNAi-knockdown of the prothoracicotropic hormone receptor, torso, in the ring gland of developing larvae leaves the timing of first and second instar molts largely unchanged, but triples duration of the third instar from 3 to 9.5 d (McBrayer et al., 2007; Rewitz et al., 2009). During this ETI period, NMJs undergo additional growth (adding >50 boutons/NMJ), and this growth remains under the control of the canonical regulators Highwire and the TGFß/BMP pathway. NMJ growth during the ETI period occurs via addition of new branches, satellite boutons, and interstitial boutons, and continues even after muscle growth levels off. Throughout the ETI, organization of synapses and active zones remains normal, and synaptic transmission is unchanged. These results establish the ETI larval system as a viable model for studying motor neuron diseases and for investigating time-dependent effects of perturbations that impair mechanisms of neuroprotection, synaptic maintenance, and response to neural injury.

Virology and molecular pathogenesis of HPV (human papillomavirus)-associated oropharyngeal squamous cell carcinoma.

The current literature fully supports HPV (human papillomavirus)-associated OPSCC (oropharyngeal squamous cell carcinoma) as a unique clinical entity. It affects an unambiguous patient population with defined risk factors, has a genetic expression pattern more similar to cervical squamous cell carcinoma than non-HPV-associated HNSCC (head and neck squamous cell carcinoma), and may warrant divergent clinical management compared with HNSCC associated with traditional risk factors. However, a detailed understanding of the molecular mechanisms driving these differences and the ability to exploit this knowledge to improve clinical management of OPSCC has not yet come to fruition. The present review summarizes the aetiology of HPV-positive (HPV+) OPSCC and provides a detailed overview of HPV virology and molecular pathogenesis relevant to infection of oropharyngeal tissues. Methods of detection and differential gene expression analyses are also summarized. Future research into mechanisms that mediate tropism of HPV to oropharyngeal tissues, improved detection strategies and the pathophysiological significance of altered gene and microRNA expression profiles is warranted.

Chest Wall Reconstruction Utilizing Ovine-derived Reinforced Tissue Matrix.

BACKGROUND: Chest wall reconstruction can be a challenge. The perfect material does not exist to restore chest wall stability. Synthetic materials have been the mainstay for reconstruction. Biological material use has increased. Recently, we initiated the use of a biosynthetic material for chest wall reconstruction that is composed of ovine-derived extracellular tissue matrix and monofilament polypropylene suture. METHODS: We respectively reviewed all patients who underwent chest wall reconstruction with a biosynthetic material from January 2020 to June 2021. RESULTS: Twenty-five patients underwent chest wall reconstruction. Median age was 35 years (range, 18 to 68); 64% were men. Indication for reconstruction was tumor resection in 10, chest wall defect after pectus repair in 7, radiation necrosis in 5, chest wall infection in 2, and lung herniation in 1. Infection was present in 28%. Median chest wall defect was 7 × 10 cm (range, 3.5 to 22.5 cm). Bioabsorbable bars were used in combination with the biosynthetic material patch in 15 patients (60%) and biosynthetic material alone in 10; 5 patients underwent myocutaneous advancement flaps. There were no operative deaths. Postoperative complications occurred in 6 patients (24%). Median hospital stay was 5 days (range, 3 to 14). Late complications occurred in 4 patients (16%). No patient had paradoxical motion, chest wall instability, or required biosynthetic material removal at a median follow-up of 12 months (range, 1 to 18). CONCLUSIONS: This novel biosynthetic material combines the benefits of biologic material and polymer reinforcement to provide a more natural chest wall reconstruction compared with mesh products made of synthetic material alone. Early results are promising in this first series in the literature.

Dehydrated Human Amnion-Chorion Membrane (Placenta) Reinforcement of Esophagectomy Anastomosis.

An anastomotic leak is a potentially fatal complication after esophagectomy. This report describes the use of a dehydrated human amnion-chorion membrane (dHACM) placenta allograft patch for reinforcement of an esophageal anastomosis. The anastomotic technique was a modified Orringer procedure through a right thoracotomy (Ivor Lewis procedure). The anastomosis was reinforced with dHACM placenta allograft. Use of the allograft prevented anastomotic leaks and loss of gastrointestinal integrity. Early results are promising.

Unclassified Neuroendocrine Tumor with a Novel CHD4::AFF2 Fusion: Expanding the Family of AFF2-Rearranged Head and Neck Malignancies.

The past decade has seen a dramatic increase in the number of new head and neck tumor entities, most of which are genetically defined. DEK::AFF2 carcinoma is one of the most recently defined neoplasms; it shows a non-keratinizing squamous morphology and occurs in the sinonasal region. We present an unusual neoplasm that was found to harbor a novel fusion involving AFF2. The case was encountered in our clinical practice. Immunohistochemistry was performed along with targeted next generation sequencing (NGS). The case presented as a metastasis to a cervical lymph node from an unknown primary, in a 49-year-old man. The tumor consisted of sheets of primitive round cells which were strongly positive for synaptophysin and chromogranin but negative for cytokeratins, S-100 protein, WT-1, desmin, and many other markers. NGS uncovered CHD4::AFF2. We found a CHD4::AFF2 fusion in a high-grade neuroendocrine tumor. Although it is just a single case, the presence of a novel fusion in a neoplasm that is otherwise not classifiable suggests that it could be a distinct entity within a possible family of AFF2-rearranged tumors. Molecular analysis should be considered for any unclassified round cell tumor in the head and neck, as additional cases will be needed to further elucidate this area.

Risk Assessment of Human Papillomavirus-Positive Cytology-Negative Cervical Cancer Screening in Black and White Women.

OBJECTIVES: As we move toward human papillomavirus (HPV) only as the preferred cervical cancer screening method, we performed a retrospective analysis of Black and White women with negative cytology (Papanicolaou negative [PAPneg]) and positive high-risk HPV (hrHPV) (HPVpos) results and determined follow-up. METHODS: We searched our pathology data system for patients with PAPneg/HPVpos results (2017-2019). Follow-up data were reviewed (39 months), and a comparison among race was performed. RESULTS: In total, 1,728 patients were identified (Black, 53%; White, 47%). Twenty-nine percent of the patients had no follow-up with no difference among the races. HPV 16 was more common among Whites (P < .01), while non-16/18 hrHPV was more common among Black patients (P = .01). A total of 30 (3.3%) Black and 26 (3.2%) White patients were diagnosed with cervical intraepithelial neoplasia grade 2/3 (CIN 2/3). More White women were diagnosed on biopsy alone (negative endocervical curettage) compared with Black women (20 vs 9, P < .01). Meanwhile, there were 21 Black and 6 White women with CIN 2/3 on endocervical curettage (P = .01). CONCLUSIONS: Follow-up of women with PAPneg/HPVpos remains a challenge. There was no disparity in follow-up when cohorts were compared. However, Black women had higher numbers of high-grade intraepithelial lesions on endocervical curettage.

Conversion to Thoracotomy During Thoracoscopic vs Robotic Lobectomy: Predictors and Outcomes.

BACKGROUND: Conversion to thoracotomy during minimally invasive lobectomy for lung cancer is occasionally necessary. Differences between video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS) lobectomy conversion have not been described. METHODS: We queried The Society of Thoracic Surgeons General Thoracic Surgery Database from January 1, 2015 to December 31, 2018. Patients with prior thoracic operations and metastatic disease were excluded. Univariable comparisons with χ2 and Kruskal-Wallis tests and multivariable logistic regression modeling were performed. RESULTS: There were 27,695 minimally invasive lobectomies from 269 centers. Conversion to thoracotomy occurred in 11.0% of VATS and 6.0% of RATS (P < .001). Conversion was associated with increased mortality (P < .001), major complications (P < .001), and intraoperative (P < .001) and postoperative (P < .001) blood transfusions. Conversion from RATS occurred emergently (P < .001) and for vascular injury (P < .001) more frequently than from VATS, but there was no difference in overall major complications or mortality. Mortality after conversion was 3.1% for RATS and 2.2% for VATS (P = .24). Clinical cancer stage II or III (P < .001), preoperative chemotherapy (P = .003), forced expiratory volume in 1 second (P = .006), body mass index (P < .001), and left-sided resection (P = .0002) independently predicted VATS conversion. For RATS clinical stage III (P = .037), left-sided resection (P = .041), and forced expiratory volume in 1 second (P = .002) predicted conversion. Lower volume centers had increased rates of conversion (P < .001) in both groups. CONCLUSIONS: Conversion from minimally invasive to open lobectomy is associated with increased morbidity and mortality. Conversion occurs more frequently during VATS compared with RATS, albeit less often emergently, and with similar rates of overall mortality and major complications. Predictors, urgency, and reasons for conversion differ between RATS and VATS lobectomy and may assist in patient selection.

Technical evaluation of a prototype ratio 29:1 grid for adult patient cardiovascular angiography imaging conditions.

The purpose of this work was to assess technical performance of a prototype high-ratio (r29), 80 line cm-1grid for imaging conditions which mimic those for adult cardiovascular angiography. The standard equipment r15, 80 line cm-1grid was used as a reference. Plastic Water®LR phantoms with thickness in the range 20-44 cm were used to simulate adult patient attenuation and scatter. Grids were tested using x-ray field of view 20 and 25 cm and x-ray source to detector distance (SID) 107 and 120 cm. The primary transmission fraction (TP) was measured using both narrow beam geometry and a lead beam stop (BS) technique. Scatter transmission (TS) was measured with the lead BS technique. The quantum signal to noise ratio improvement factor (KSNR) was used to describe relative grid performance. The experimental conditions required revised theory to assess grid performance. Theory to account for the detector glare and underestimation of scatter intensity by the lead BS method was developed. Also, novelKSNRtheory was developed to allow direct comparison of two grids operated at different SID. MeanTPwas modestly lower for the r29 versus r15 grid (0.69 versus 0.75). When tested under equivalent scatter condition, TSof the r29 grid was approximately ½ that of the r15 grid (0.18 versus 0.34).KSNRof the r29 grid at SID 120 cm compared to the r15 grid at SID 107 cm increased linearly with phantom thickness (range 1.0 to ∼1.16). Findings of this work indicate that the r29 grid used at SID 120 cm is expected to provide improved image quality (or reduced patient radiation dose) when compared to the r15 grid used at SID 107 cm for adult cardiovascular patients and that the potential benefit of the r29 grid increases with patient thickness >20 cm.

Renal medullary carcinoma involving serous cavity fluids: a cytomorphologic study of 12 cases.

INTRODUCTION: Renal medullary carcinoma (RMC) is a highly lethal adenocarcinoma with a propensity for widespread metastatic disease in young patients. It is strongly associated with sickle cell trait and shows the loss of SMARCB1 (also known as INI1 or BAF47) protein expression. In the present study, we reviewed a series of 12 patients for whom the cytology specimens played a significant role in patient treatment. MATERIALS AND METHODS: We performed a retrospective case review of patients with a history of RMC from 3 large tertiary care pathology practices. RESULTS: A total of 12 patients were identified with histologically confirmed RMC who had had pleural, pericardial, or urine specimens involved by their disease or had undergone initial kidney fine needle aspiration. Patient age ranged from 13 to 37 years (median, 21.5 years). All 12 patients were black or of African descent, and 10 had a confirmed history of sickle cell trait. Of the 12 patients, 11 (92%) had fluid specimens involved by metastatic tumor at some point in their clinical course, and 4 (33%) had initially presented with pericardial and/or pleural effusions or urine specimens that were positive for malignancy. Cytologic examination predominantly showed fragments of 3-dimensional "tumor balls" with smooth borders, fine pale cytoplasm with vacuolization, and highly pleomorphic nuclei with irregular nuclear membranes and coarse to vesicular chromatin and single prominent nucleoli. CONCLUSIONS: The cytomorphology of RMC involving serous fluids is nonspecific and in keeping with metastatic high-grade adenocarcinoma. In a young patient presenting with no history of malignancy and a pleural or pericardial effusion, triaging the material for ancillary studies and a nuanced assessment of patient history and radiologic findings will be critical.

The adenoviral E1B 55-kilodalton protein controls expression of immune response genes but not p53-dependent transcription.

The human adenovirus type 5 (Ad5) E1B 55-kDa protein modulates several cellular processes, including activation of the tumor suppressor p53. Binding of the E1B protein to the activation domain of p53 inhibits p53-dependent transcription. This activity has been correlated with the transforming activity of the E1B protein, but its contribution to viral replication is not well understood. To address this issue, we used microarray hybridization methods to examine cellular gene expression in normal human fibroblasts (HFFs) infected by Ad5, the E1B 55-kDa-protein-null mutant Hr6, or a mutant carrying substitutions that impair repression of p53-dependent transcription. Comparison of the changes in cellular gene expression observed in these and our previous experiments (D. L. Miller et al., Genome Biol. 8:R58, 2007) by significance analysis of microarrays indicated excellent reproducibility. Furthermore, we again observed that Ad5 infection led to efficient reversal of the p53-dependent transcriptional program. As this same response was also induced in cells infected by the two mutants, we conclude that the E1B 55-kDa protein is not necessary to block activation of p53 in Ad5-infected cells. However, groups of cellular genes that were altered in expression specifically in the absence of the E1B protein were identified by consensus k-means clustering of the hybridization data. Statistical analysis of the enrichment of genes associated with specific functions in these clusters established that the E1B 55-kDa protein is necessary for repression of genes encoding proteins that mediate antiviral and immune defenses.

Reoperative Pectus Repair Using Biomaterials.

BACKGROUND: Reoperation after failed pectus repair, Open or Nuss, is complex. In the majority of patients, metal bars or plates are used. Recently, an absorbable bar (poly-L-lactide [PLA]) was introduced for rib fixation. This series is my experience of using this biomaterial for reoperative pectus surgery. METHODS: We respectively reviewed the medical records of all patients who were referred to our institution for pectus abnormalities; 180 patients were evaluated, 62 patients (34%) underwent reoperation. RESULTS: Sixty-two patients underwent reoperative Open repair. Median age was 38 years (range 18-, 72 years); 39 (63%) were men. Thirty-two patients had Open repair for recurrent pectus using posterior sternal support with PLA bars, and 30 patients with acquired restrictive thoracic dystrophy had expansion surgery with multiple PLA bars. Median hospital stay was 7 days (4-21 days). Postoperative complications occurred in 22 patients (35%); late complications in 10 patients (16%); all required reoperation for incisional or soft tissue issues. No patient required reoperation for a pectus or acquired restrictive thoracic dystrophy recurrence. Patient satisfaction was excellent in 85%, good in 8%, fair in 4%, and poor in 3%. CONCLUSIONS: Reoperative pectus surgery is complex and requires a detailed preoperative evaluation and individualized plan for correction. Use of PLA absorbable bars for sternal support and chest cavity expansion provides a safe alternative. Soft tissue complications are common and reversible; early results are promising in these challenging patients.

WITHDRAWN: Dehydrated Human Amnion/Chorion Membrane (Placenta) Reduces Anastomotic Leaks after Esophagectomy.

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Primary pancreatic Ewing sarcoma: a cytomorphologic and histopathologic study of 13 cases.

INTRODUCTION: Ewing sarcoma (ES) is a small, round cell sarcoma that rarely occurs in solid organs, including the pancreas. A diagnostic overlap exists with other primary pancreatic neoplasms, especially for specimens from small biopsies and fine needle aspiration (FNA). To improve the diagnosis of this rare pancreatic tumor, we have reported a series of 13 cases of primary pancreatic ES and reviewed the cytopathologic, surgical pathology, clinical, and radiologic features of these neoplasms. MATERIALS AND METHODS: We performed a retrospective case review of 13 patients with a diagnosis of pancreatic ES from 2 tertiary academic medical centers. A combination of cytology and histopathologic slides were reviewed, and the patient demographics, clinical information, somatic genetics, and radiologic findings were obtained from the electronic medical records. RESULTS: Five FNA specimens from 5 patients and 8 surgical biopsy or resection specimens were identified and reviewed. The patients included 9 males and 4 females, with a median age of 27 years (range, 15-78 years). The cytology smears were highly cellular and showed a combination of complex tissue fragments and singly dispersed small round blue cells. The final diagnosis was ES for all 5 FNA specimens in accordance with the characteristic cytomorphology, diffuse and/or strong membranous immunolabeling for CD99, membranous ß-catenin, and molecular confirmation of EWSR1 using fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction. CONCLUSIONS: The cytologic diagnosis of ES is challenging, especially in unusual locations such as the pancreas. However, the correct cytologic diagnosis is important because these patients will require neoadjuvant therapy before surgery. Confirmatory molecular studies should be required to render the diagnosis of pancreatic ES.

Malignant teratomas of the thyroid gland: clinico-radiologic and cytomorphologic features of a rare entity.

INTRODUCTION: Primary thyroid gland malignant teratomas are extremely rare and can pose diagnostic challenges on fine needle aspiration (FNA) due to their cytomorphologic heterogeneity. Recent next generation sequencing studies have identified recurrent DICER1 hotspot mutations in these tumors, suggesting that malignant teratomas of the thyroid should be considered a distinct pathological entity. Herein, we review the clinico-radiologic and FNA findings in a series of DICER1 mutated malignant teratomas. METHODS: We performed a retrospective case review of 9 FNAs from 5 patients with a histologically confirmed malignant teratoma of the thyroid gland from 2 large tertiary care pathology practices. RESULTS: The patients included 4 females and 1 male, with an average age of 43 years (22-65 years). The nodules were centered within the thyroid gland and ranged from 1.7 to 10 cm in diameter. FNAs of primary thyroid teratomas demonstrate marked cellularity, epithelial proliferations, an absence of colloid, and a predominance of immature spindled cells, representing the mesenchymal and neural ectodermal components of these tumors. The FNA interpretations ranged from atypia of undetermined significance to overtly malignant. Three patients died of their disease and 2 are alive with no evidence of disease. CONCLUSIONS: Malignant thyroid teratoma is a rare entity with cytomorphologic overlap with other high-grade neoplasms of the thyroid. Recent molecular studies have defined recurrent DICER1 mutations in malignant thyroid teratomas and propose these as a distinct clinicopathological entity. The features described here may be helpful in providing a correct prospective interpretation.