Background
Thyroid nodules have a low prevalence of malignancy and most proven cancers do not behave aggressively. Thus, risk‐stratification of nodules is a critical step to avoid surgical ...overtreatment. We hypothesized that a risk management system superior to those currently in use could be created to reduce the number of clinically indeterminate nodules (i.e., the “gray zone”) by concurrently considering the malignancy risks conferred by clinical, ultrasonographic, and cytologic variables.
Methods
Thyroidectomy cases were reviewed from three institutions. Their benign versus malignant outcome was used to evaluate the variables for correlation. A binary logistic regression model was trained and, using indeterminate nodules with Bethesda III and IV results, validated. A scoring nomogram was designed to demonstrate the application of the model in clinical practice.
Results
One hundred thirty thyroidectomies (28% malignant) met inclusion criteria. The final logistic regression model included difficulty in swallowing, hypothyroidism, echogenicity, hypervascularity, margins, calcification, and cytology diagnosis as input parameters. The model was highly successful in determining the outcome (p value: 0.001) with a R2(Nagelkerke) score of 0.93. The area under the curve as determined by receiver operating characteristics was 0.91. The accuracy of the model on the training dataset was 93% (sensitivity and specificity 92% and 96%, respectively) and, on the validation dataset, 80% (sensitivity and specificity 91% and 67%, respectively).
Conclusions
We report a model for risk assessment of thyroid nodules that has the potential to significantly reduce indeterminates and surgical overtreatment. We illustrate its application via a straightforward nomogram, which integrates clinical, ultrasonographic, and cytologic data, and can be used to create clear, evidence‐based management plans for patients.
A nomogram based on clinical, radiological, and cytological variables provides individualized malignancy risk assessments and management plans for patients with thyroid nodules. This approach may translate into a reduction of indeterminate cytology results and decrease unnecessary surgical intervention.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
Thyroid malignancy is one of the most common types of cancer in developed nations. Currently, fine‐needle aspiration cytology (FNAC) is the most practical screening test for thyroid ...nodules. However, cytologically indeterminate samples comprise approximately 15%–30% of cases. These include cases classified as atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM). Indeterminate cases can be sent for molecular testing for more definitive classification to help guide management and prevent overtreatment of benign thyroid nodules. We conducted a retrospective review on molecular testing of indeterminate thyroid FNAC and reviewed subsequent histologic diagnoses in resection specimens to assess how molecular testing supported a diagnosis and its effect on clinical management of patients at our institution.
Methods
A retrospective chart review was performed on all thyroid FNAC specimens, corresponding molecular testing, and subsequent surgical resection specimens over a 6‐year period.
Results
A total of 10,253 thyroid FNAC were performed in our hospital system during our study period, of which 10% (n = 1102/10,253) had indeterminate FNAC results. Molecular testing was performed in 16% (n = 178/1102) of indeterminate cytology cases. Genetic alterations were identified in 39% (n = 69/178) of the cases sent for molecular testing. The majority of cytologically indeterminate cases sent for molecular testing were follicular‐patterned lesions and their corresponding resection specimens revealed mostly low grade follicular derived neoplasms (i.e., follicular adenoma, non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features, and follicular variant of papillary thyroid carcinoma). Of the cases with identified genetic alterations, 75% (n = 52/69) were treated surgically. In cases with no genetic alterations identified, only 18% (n = 20/109) were treated surgically.
Discussion/Conclusion
Molecular testing on cytologically indeterminate thyroid nodules can help provide a more accurate risk of malignancy assessment in patients with lesions that are difficult to diagnosis based solely on FNAC morphology. The types of genetic alterations identified in the resected thyroid lesions were consistent with what has been previously described in the literature. Additionally, we found that in the patients with indeterminate thyroid FNAC with adjunct molecular testing, more than half did not undergo surgical resection. This finding emphasizes the value of adding molecular testing in patients, particularly when attempting to reduce unnecessary surgical intervention.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Many institutions have cytopathology case archives for education. Unfortunately, these slides deteriorate over time and have limited accessibility. Whole slide imaging (WSI) can overcome these ...limitations. However, suboptimal image quality and scanning effort are barriers.
We selected 123 slides from cytopathology study sets for WSI scanning at 400x magnification without z-stacking. The Ventana DP 200 scanner and Virtuoso software were used. Slides were scanned in 2 rounds: the first round of slides was prepared for scanning with light cleaning, and the second round was performed only on slides that had unacceptable WSI quality after thorough cleaning. Slides were assessed with a 4-tier grading system created by the authors. Time to scan each slide was recorded.
Within the first round, 96 of 123 (78%) slides scanned were determined to be of acceptable quality. After the second round of scanning, in total, 118 of 123 (95.9%) slides were determined to be of acceptable quality. The average time needed to scan each slide was 213 seconds.
The majority of slides scanned were of acceptable quality in the first round of scanning. After cleaning and rescanning, nearly every slide investigated was of acceptable quality. The primary objective is to provide other institutions that may be considering a similar project a benchmark so that they know what to expect in terms of slide scan success rate and the amount of time needed to digitize slides for educational archiving. This pilot study demonstrates the feasibility of using WSI for cytology education cases.
•Cytopathology slides can be scanned in a timely manner to create whole slide imaging (WSI) of acceptable quality for educational purposes.•Acceptable quality WSI can be obtained even without Z-stacking.•WSI would be a viable method for institutions to archive their cytopathology glass slides.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Objectives
To investigate the pre‐analytics of the molecular testing of cytology specimens, we studied the effects of time in refrigerator storage (4°C) of malignant effusions on RNA ...sequencing (RNAseq) results.
Methods
Ten effusion specimens were stored in a refrigerator (4°C) for different durations (day 0, 1, 4, and 7). All specimens were prepared as cytospins fixed in either Carnoy's solution or 95% ethanol (EtOH) and in an RNA preservative for a fresh frozen (FF) high‐quality reference. Whole transcriptome (wt) and targeted (t)RNAseq of two multigene expression signatures were performed. We then compared transcript expression levels (including mutant allele fraction) according to pre‐analytical variables using a concordance correlation coefficient (CCC) and a mixed effect model.
Results
Sequencing results were mostly stable over increasing time in storage. Cytospins fixed in Carnoy's solution were more concordant with FF samples than cytospins fixed in 95% EtOH at all timepoints. This finding was consistent for both wtRNAseq (averages: day 0 CCC = 0.98 vs 0.91; day 7 CCC = 0.88 vs 0.78) and tRNAseq methods (averages: day 0 CCC = 0.98 vs 0.81; day 7 CCC = 0.98 vs 0.90). Cytospins fixed in Carnoy's solution did not show significant changes in expression over timepoints or between expression signatures, whereas 95% EtOH did.
Conclusion
RNAseq can be accurately performed on effusion specimens after prolonged refrigerator storage. RNA extracted from scraped cytospin slides fixed in Carnoy's solution was marginally superior to 95% EtOH fixation, but either method had comparable analytic performance to high‐quality FF RNA samples.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
RNA sequencing (RNAseq) analysis is emerging as a clinical research or diagnostic approach for cytologic samples, but there is need for formal comparison of different sample preparation methods in ...the cytology laboratory to identify which pre-analytic methods could provide alternatives to formalin-fixed paraffin-embedded (FFPE) sections.
We prepared 13 malignant effusions (metastatic estrogen receptor-positive breast cancer) in the cytology laboratory using 6 routine cytologic methods: FFPE cell block, Carnoy’s solution, 95% ethanol (EtOH), air-dried and Diff-Quik, ThinPrep, and SurePath preparations. Measurements of RNA quality, expression of 2 multigene expression signatures, molecular subtype, and 4 common activating mutation sites in each preparation were compared with fresh frozen (FF) cell pellet in RNA preservative using distribution of fragment length and concordance correlation coefficient (CCC).
The fraction of RNA fragments measuring 200 bases or more (DV200) were 24% higher from cytospins fixed in Carnoy’s solution or 95% EtOH than DV200 from FFPE cell blocks. SurePath samples failed RNAseq quality control. There was high concordance of gene expression measurements with FF samples using cytospins fixed in Carnoy's solution, 95% EtOH, Diff-Quik (CCC = 0.829, 0.812, 0.760, respectively), or ThinPrep (CCC = 0.736), but lower using FFPE cell block (CCC = 0.564). The proportion of mutant transcripts was concordant between FF and any cytologic preparation methods.
Cytospin preparations fixed with Carnoy’s or 95% ETOH then Papanicolaou stained produced RNAseq results that were equivalent to FF samples and superior to FFPE cell block sections.
•Routine cytologic slide preparations can produce RNA sequencing results that are superior to formalin-fixed paraffin-embedded cell block preparations.•Cytology effusion specimens can be a source of high quantity and quality material for RNA sequencing analysis.•This information is critically important as cancer treatments are trending towards personalized, targeted therapies.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•High CD4 count does not necessarily protect against aggressive AIDS-defining diseases, particularly, HIV-associated Kaposi sarcoma.•Extremely elevated HHV-8, HIV, and EBV viral loads could predict ...aggressive HIV-associated KS disease course.•Anemia and thrombocytopenia in HIV/AIDS could be autoimmune like ITP and AIHA or bone marrow infiltration-related, by Kaposi sarcoma, for instance, or both.
Bone marrow infiltration by Kaposi sarcoma (KS) in human immunodeficiency virus (HIV) patients is rare, with only a few cases reported in patients with a CD4 count greater than 200 cells/ml. To the best of our knowledge, this is the first reported case of bone marrow involvement in HIV-associated KS in which the CD4 count is greater than 400 cells/ml. In this article, we present a patient with HIV-associated KS with skin, lymph node, bone, pulmonary, gastrointestinal, and bone marrow involvement despite a high CD4 count. This is the highest CD4 count associated with bone marrow invasion in the medical literature. A high CD4 count does not protect untreated HIV patients against aggressive, diffuse KS-related lesions, including bone marrow infiltration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Heterotopic ossification is a rare, reactive condition, sometimes classified as a “pseudotumor,” involving the formation of bone within the soft tissues (
Int J Surg Case Rep
...2014;5:476–479), This process can occur as an undesirable pathologic sequela of trauma and surgery (
J Am Acad Orthop Surg
2004;12:116–125). The few cases reported in the literature are almost exclusively in men with a predominance in people of African ancestry (
J Am Acad Orthop Surg
2004;12:116–125;
Bone Joint J
2016;98-B:761–766;
Case Rep Surg
2019;2019:4036716). Reports of heterotopic ossification have been described in medical literature since 1692 as myositis ossificans progressiva (
JBJS
1938;20:661–674). It was not until 1999 that the term “heterotopic mesenteric ossification” was formally used by Wilson et al to describe a complication found in post–abdominal surgical patients (
Am J Surg Pathol
1999;23:1464–1470). Although the exact pathologic mechanism of heterotopic mesenteric ossification has not been elucidated, some hypotheses include differentiation of mesenchymal progenitor cells toward an osteogenic lineage, as well as proliferation of dislocated fragments of bone from other regions of the body (
J Gastrointest Surg
2015;19:579–580). Since the late 1900s, fewer than 40 cases of mesenteric ossification have been reported. Limited gross and histologic description is available for pathologists and surgeons to identify this phenomenon; however, further data can be acquired at autopsy. Awareness of this condition on the part of clinicians, and early review and recognition by pathologists, may alter surgical management decisions and improve upon morbidity and mortality in these patients. We present gross and histologic examination of an advanced case of heterotopic ossification at autopsy, with a review of current management recommendations.
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