Grading of Medullary Thyroid Carcinoma: an Interobserver Reproducibility Study

Williams, Jessica F; Zhao, Melissa; Najdawi, Fedaa; Ahmadi, Sara; Hornick, Jason L.; Wong, Kristine; Barletta, Justine A.

doi:10.1007/s12022-022-09718-0

Cited by 16 publications

(6 citation statements)

References 31 publications

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“…3 and Table 2) [53]. The IMTCGS system has been validated in other series [54] and appears well reproducible [55]. In conclusion, recent findings have demonstrated that Ki67 labelling index plays a prognostic role in MTC, although the better prognostic stratification of patients is obtained combining Ki67 index with necrosis (IMTCGS system).…”

Section: Medullary Thyroid Carcinomamentioning

confidence: 64%

Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Rosa

2023

Endocr Pathol

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The introduction of Ki67 immunohistochemistry in the work-up of neuroendocrine neoplasms (NENs) has opened a new approach for their diagnosis and prognostic evaluation. Since the first demonstration of the prognostic role of Ki67 proliferative index in pancreatic NENs in 1996, several studies have been performed to explore its prognostic, diagnostic, and predictive role in other neuroendocrine and endocrine neoplasms. A large amount of information is now available and published results globally indicate that Ki67 proliferative index is useful to this scope, although some differences exist in relation to tumor site and type. In gut and pancreatic NENs, the Ki67 proliferative index has a well-documented and accepted diagnostic and prognostic role and its evaluation is mandatory in their diagnostic work-up. In the lung, the Ki67 index is recommended for the diagnosis of NENs on biopsy specimens, but its diagnostic role in surgical specimens still remains to be officially accepted, although its prognostic role is now well documented. In other organs, such as the pituitary, parathyroid, thyroid (follicular cell-derived neoplasms), and adrenal medulla, the Ki67 index does not play a diagnostic role and its prognostic value still remains a controversial issue. In medullary thyroid carcinoma, the Ki67 labelling index is used to define the tumor grade together with other morphological parameters, while in the adrenal cortical carcinoma, it is useful to select patients to treated with mitotane therapy. In the present review, the most important information on the diagnostic, prognostic, and predictive role of Ki67 proliferative index is presented discussing the current knowledge. In addition, technical issues related to the evaluation of Ki67 proliferative index and the future perspectives of the application of Ki67 immunostaining in endocrine and neuroendocrine neoplasms is discussed.

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Section: Medullary Thyroid Carcinomamentioning

confidence: 64%

Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Rosa

2023

Endocr Pathol

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“…A reproducible and reliable grading system is necessary to correlate histologic findings with prognosis in both human medicine [12][13][14][15][16][17] and veterinary medicine. [18][19][20][21] The reproducibility of the human meningioma grading system applied to canine meningioma was previously investigated to lay the groundwork for studies on the prognostic significance of histologic grade in canine meningiomas.…”

Section: Introductionmentioning

confidence: 99%

Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria

Belluco,

Marano,

Lurier

et al. 2023

Vet Comparative Oncology

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Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter‐observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter‐observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine‐specific guidelines increased the inter‐observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter‐observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

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“…Williams et al . recently demonstrated excellent intraobserver agreement of manual assessment of the Ki67 proliferation index with a kappa value of 0.86 in a cohort of 44 MTC 4 . However, manual Ki67 count is known to be tedious and time‐consuming.…”

Section: Introductionmentioning

confidence: 98%

“…Williams et al recently demonstrated excellent intraobserver agreement of manual assessment of the Ki67 proliferation index with a kappa value of 0.86 in a cohort of 44 MTC. 4 However, manual Ki67 count is known to be tedious and time-consuming. Various digital image analysis platforms and machine learning (ML)-based algorithms have shown to be highly sensitive and specific to obtain an automatic reading of the Ki67 index in pancreatic neuroendocrine neoplasms and breast carcinomas.…”

Section: Introductionmentioning

confidence: 99%

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

Nadeem,

Hanna,

Viswanathan

et al. 2023

Histopathology

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AimsThe International Medullary Thyroid Carcinoma Grading System, introduced in 2022, mandates evaluation of the Ki67 proliferation index to assign a histological grade for medullary thyroid carcinoma. However, manual counting remains a tedious and time‐consuming task.Methods and resultsWe aimed to evaluate the performance of three other counting techniques for the Ki67 index, eyeballing by a trained experienced investigator, a machine learning‐based deep learning algorithm (DeepLIIF) and an image analysis software with internal thresholding compared to the gold standard manual counting in a large cohort of 260 primarily resected medullary thyroid carcinoma. The Ki67 proliferation index generated by all three methods correlate near‐perfectly with the manual Ki67 index, with kappa values ranging from 0.884 to 0.979 and interclass correlation coefficients ranging from 0.969 to 0.983. Discrepant Ki67 results were only observed in cases with borderline manual Ki67 readings, ranging from 3 to 7%. Medullary thyroid carcinomas with a high Ki67 index (≥ 5%) determined using any of the four methods were associated with significantly decreased disease‐specific survival and distant metastasis‐free survival.ConclusionsWe herein validate a machine learning‐based deep‐learning platform and an image analysis software with internal thresholding to generate accurate automatic Ki67 proliferation indices in medullary thyroid carcinoma. Manual Ki67 count remains useful when facing a tumour with a borderline Ki67 proliferation index of 3–7%. In daily practice, validation of alternative evaluation methods for the Ki67 index in MTC is required prior to implementation.

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Grading of Medullary Thyroid Carcinoma: an Interobserver Reproducibility Study

Cited by 16 publications

References 31 publications

Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future

Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria

Ki67 proliferation index in medullary thyroid carcinoma: a comparative study of multiple counting methods and validation of image analysis and deep learning platforms

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