The study by Hang et al, published in this issue of Cancer Cytopathology, is a timely multi‐insti... more The study by Hang et al, published in this issue of Cancer Cytopathology, is a timely multi‐institutional study that proposes a modified scheme for subcategorizing the diagnostic category of salivary gland neoplasm of uncertain malignant potential (SUMP) of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). This editorial introduces the current study with a brief overview of the MSRSGC and the SUMP category.
A pediatric cytopathology symposium was held at the recent 20th International Congress of Cytolog... more A pediatric cytopathology symposium was held at the recent 20th International Congress of Cytology, which convened in Sydney, Australia, in May 2019. This educational event brought together cytopathologists from different countries and different institutions to discuss some of the practical considerations when applying current diagnostic classification systems to cytopathology specimens from young (pediatric and adolescent) patients. Within the past decade, various classification systems have been developed to create more standardized terminology for cytopathology specimen reporting among institutions, which can lead to improved management guidelines based on evidence‐based medicine. It is well known that a majority of the peer‐reviewed publications in cytopathology discussing the usefulness of these classification schemes predominantly contain case cohorts of adult patients. Although pediatric cases are not excluded from following these diagnostic guidelines, there is less of an em...
ObjectivesWe investigated the clinical significance of thyroid‐stimulating hormone receptor (TSHR... more ObjectivesWe investigated the clinical significance of thyroid‐stimulating hormone receptor (TSHR) mutations detected in thyroid fine needle aspiration (FNA) specimens.MethodsThe pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations.ResultsA total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty‐two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium‐iodide transporter (NIS) mRNA was in the range of 0.01%–62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow‐up was available in five cases (all benign except one). On follow‐up available for 38 cases (mean: 24 months; range: 7–47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size.ConclusionsTSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.
Page 1. 341 OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the d... more Page 1. 341 OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the diagnosis of papillary micro-carcinoma. STUDY DESIGN: Eight cases of papillary microcarci-noma were diagnosed by fine needle aspiration. ...
Introduction: The diagnostic utility of molecular profiling for the evaluation of indeterminate p... more Introduction: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis. Methods: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children’s Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics. Results: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p < 0.01), performance of lymph node dissection (p < 0.01), histological diagnosis (p < 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) Pediatric Guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration. Conclusions: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.
International Journal of Surgical Pathology, Jul 1, 1999
Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular... more Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular lesions with different patterns, a peculiar appearance of the surrounding nonnodular thyroid tissue, and the presence of features suspicious for carcinoma. Such features are caused by a high serum level of TSH (thyroid-stimulating hormone) in response to defects in the production of the thyroid hormone. The pathophysiology of DG is described, with regard to the hyperplastic and oncogenetic mechanisms attributed to TSH. The various histopathological features are reviewed, in particular those that help in differentiating the hypercellular nodules of DG from differentiated thyroid carcinoma. The literature on the histopathology of DG is reviewed and clues to avoid inappropriate overdiagnosis of malignancy are given.
Background In a previous worldwide survey, the authors showed a drastic reduction in the number o... more Background In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 “lockdown” period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow‐up worldwide survey collecting data from the post‐lockdown period (2020). Methods Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post‐lockdown period (2020), which ranged from April 4 to October 31. Differences between the post‐lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions The data showed a persistent reduction in the cytological specimen volume during the post‐lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post‐lockdown is a promising finding of a slow return to normality.
BackgroundTo the authors' knowledge, the impact of the coronavirus disease 2019 (COVID‐19) pa... more BackgroundTo the authors' knowledge, the impact of the coronavirus disease 2019 (COVID‐19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported.MethodsData regarding the activity of each cytopathology laboratory during 4 weeks of COVID‐19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine‐needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta‐analytical approach.ResultsOverall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%‐98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conve...
The study by Hang et al, published in this issue of Cancer Cytopathology, is a timely multi‐insti... more The study by Hang et al, published in this issue of Cancer Cytopathology, is a timely multi‐institutional study that proposes a modified scheme for subcategorizing the diagnostic category of salivary gland neoplasm of uncertain malignant potential (SUMP) of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC). This editorial introduces the current study with a brief overview of the MSRSGC and the SUMP category.
A pediatric cytopathology symposium was held at the recent 20th International Congress of Cytolog... more A pediatric cytopathology symposium was held at the recent 20th International Congress of Cytology, which convened in Sydney, Australia, in May 2019. This educational event brought together cytopathologists from different countries and different institutions to discuss some of the practical considerations when applying current diagnostic classification systems to cytopathology specimens from young (pediatric and adolescent) patients. Within the past decade, various classification systems have been developed to create more standardized terminology for cytopathology specimen reporting among institutions, which can lead to improved management guidelines based on evidence‐based medicine. It is well known that a majority of the peer‐reviewed publications in cytopathology discussing the usefulness of these classification schemes predominantly contain case cohorts of adult patients. Although pediatric cases are not excluded from following these diagnostic guidelines, there is less of an em...
ObjectivesWe investigated the clinical significance of thyroid‐stimulating hormone receptor (TSHR... more ObjectivesWe investigated the clinical significance of thyroid‐stimulating hormone receptor (TSHR) mutations detected in thyroid fine needle aspiration (FNA) specimens.MethodsThe pathology archives at our institution were reviewed between 2018 and 2021 for indeterminate (Bethesda category III and IV) specimens with Thyroseq® analysis showing TSHR mutations.ResultsA total of 2184 cases diagnosed as atypia/follicular lesion of undetermined significance (AUS/FLUS), and 2625 diagnosed as follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) were identified. A total of 1735 AUS/FLUS and 2339 SFN/FN underwent Thyroseq® analysis; 69 showed TSHR mutations (1.6%, 59 female, 10 male, average age: 55 years). Ten cases showed oncocytic features. Twelve patients underwent radionuclide scans within 1 year of FNA:11 were hyperfunctioning. Nodule size and TSH levels were weakly correlated. Twenty‐two different TSHR mutations were identified (most common: M453T). A second mutation was found in five cases (EZH1 n = 2, and EIF1AX n = 3). The expression of sodium‐iodide transporter (NIS) mRNA was in the range of 0.01%–62.43% out of all sequencing reads, and was elevated in 49 (71%) cases. Surgical pathology follow‐up was available in five cases (all benign except one). On follow‐up available for 38 cases (mean: 24 months; range: 7–47 months), 34 (89.5%) nodules remained stable and 3 (8%) increased in size.ConclusionsTSHR mutations in thyroid FNA samples classified as indeterminate are rare, generally benign, and commonly associated with autonomy on scan if performed.
Page 1. 341 OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the d... more Page 1. 341 OBJECTIVE: To assess the role of fine needle aspiration (FNA) of the thyroid in the diagnosis of papillary micro-carcinoma. STUDY DESIGN: Eight cases of papillary microcarci-noma were diagnosed by fine needle aspiration. ...
Introduction: The diagnostic utility of molecular profiling for the evaluation of indeterminate p... more Introduction: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis. Methods: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children’s Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics. Results: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p &lt; 0.01), performance of lymph node dissection (p &lt; 0.01), histological diagnosis (p &lt; 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) Pediatric Guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration. Conclusions: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.
International Journal of Surgical Pathology, Jul 1, 1999
Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular... more Dyshormonogenetic goiter (DG) presents a pathological picture characterized by many solid nodular lesions with different patterns, a peculiar appearance of the surrounding nonnodular thyroid tissue, and the presence of features suspicious for carcinoma. Such features are caused by a high serum level of TSH (thyroid-stimulating hormone) in response to defects in the production of the thyroid hormone. The pathophysiology of DG is described, with regard to the hyperplastic and oncogenetic mechanisms attributed to TSH. The various histopathological features are reviewed, in particular those that help in differentiating the hypercellular nodules of DG from differentiated thyroid carcinoma. The literature on the histopathology of DG is reviewed and clues to avoid inappropriate overdiagnosis of malignancy are given.
Background In a previous worldwide survey, the authors showed a drastic reduction in the number o... more Background In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 “lockdown” period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow‐up worldwide survey collecting data from the post‐lockdown period (2020). Methods Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post‐lockdown period (2020), which ranged from April 4 to October 31. Differences between the post‐lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions The data showed a persistent reduction in the cytological specimen volume during the post‐lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post‐lockdown is a promising finding of a slow return to normality.
BackgroundTo the authors' knowledge, the impact of the coronavirus disease 2019 (COVID‐19) pa... more BackgroundTo the authors' knowledge, the impact of the coronavirus disease 2019 (COVID‐19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported.MethodsData regarding the activity of each cytopathology laboratory during 4 weeks of COVID‐19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine‐needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta‐analytical approach.ResultsOverall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%‐98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conve...
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