Negative Parafibromin Staining Predicts Malignant Behavior in Atypical Parathyroid Adenomas

Kruijff, Schelto; Sidhu, Stan; Sywak, Mark; Gill, Anthony J.; Delbridge, Leigh

doi:10.1245/s10434-013-3288-8

Cited by 84 publications

(83 citation statements)

References 22 publications

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“…However, with recent developments in molecular pathology and ancillary tools, the classification of these borderline tumours has been greatly refined 153. When used in the appropriate clinical and pathological setting, ancillary biomarkers serve a crucial role in the distinction of malignancy in these borderline tumours, thereby enhancing the accuracy of the pathological examination 38 42 43 45 46 98 99 155 156 158–161…”

Section: Pathological Manifestations Of Hyperparathyroidismmentioning

confidence: 99%

“…Based on the currently available evidence and our own experiences , loss-of-expression of retinoblastoma protein (Rb), Bcl-2a, p27, parafibromin, mdm2 and APC, as well as increased MIB-1 (Ki67) proliferative index >5%, overexpression of p53 and positivity for galectin-3 (in the absence of multiglandular disease) favours a diagnosis of malignancy in a parathyroid neoplasm with worrisome histopathological features 31 33 38 42–46 49 87 98 99 141 153 155 156 158–164. In particular, the use of parafibromin immunostain (figure 8E) is very helpful to differentiate between parathyroid adenomas (intact nuclear and nucleolar parafibromin expression) and parathyroid carcinomas (complete loss of nuclear or nucleolar parafibromin expression) 38 42 43 46 98 99 153 156 159 161 162.…”

Section: Pathological Manifestations Of Hyperparathyroidismmentioning

confidence: 99%

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Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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Section: Pathological Manifestations Of Hyperparathyroidismmentioning

confidence: 99%

Section: Pathological Manifestations Of Hyperparathyroidismmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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“…In this study, the specificity of parafibromin staining would decrease to 63 % if only atypical adenoma was used as the control, while the pooled specificity was 95 % if other benign lesions were also included. Recently, it was reported that negative parafibromin staining might predict recurrence of PTCA as well as atypical adenomas [26]. The authors suggested that atypical adenoma with negative parafibromin staining should be treated as tumor with low malignant potential.…”

Section: Discussionmentioning

confidence: 99%

“…1. From 286 potentially relevant publications, a total of 10 studies were eligible for data extraction and analysis [15][16][17][23][24][25][26][27][28][29]. The characteristics of these included …”

Section: Eligible Articlesmentioning

confidence: 99%

Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis

Liao

Cao

et al. 2016

Endocrine

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It is a challenge to distinguish parathyroid carcinoma (PTCA) from benign parathyroid lesions without recurrence or metastasis. Parafibromin immunohistochemical (IHC) staining had been described for the diagnosis of PTCA. But great variations existed in the reported sensitivity and specificity among different studies. We conducted a meta-analysis to summarize the diagnostic accuracy of parafibromin staining for PTCA. Published studies from Pubmed, Embase, and Cochrane Library were searched using the combination of terms "parafibromin," "CDC73," "HRPT2," and "parathyroid." Pooled sensitivity and specificity with 95 % confidence interval (CI) were calculated and the summary receiver operator characteristic (SROC) curves were constructed. The heterogeneity among included studies was evaluated and possible reasons were explored by meta-regression. A total of 10 studies including 202 patients with PTCA were finally enrolled in this meta-analysis. For parafibromin staining, sensitivity varied from 29 to 100 % (pooled estimate of 68 %; 95 % CI 49-82 %) and specificity ranged from 61 to 100 % (pooled estimate of 95 %; 95 % CI 85-98 %). The AUC for parafibromin staining was 0.91 (95 % CI 0.88-0.93). A significant heterogeneity was observed among included studies. According to meta-regression analysis, the scoring criteria and parafibromin antibody used in IHC were the covariates influencing the sensitivity. And the specificity decreased if atypical parathyroid adenomas were included in the control groups. The specificity of parafibromin staining was satisfactory for diagnosis of PTCA, while the sensitivity was limited. We suggested that a standardized IHC protocol and scoring system criteria should be applied in future studies to improve the diagnostic performance of parafibromin staining.

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“…В работе S. Kruijff и соавт. [19] рецидив ПГПТ документирован в 3,7% (2/53) случаев. Стоит отметить, что в данном исследовании возврат болез-ни был зафиксирован только в 10% (2/21) парафи-бромин-негативных образований.…”

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Two cases synchronous atypical parathyroid adenomas and papillary thyroid carcinoma

et al. 2018

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Наиболее часто первичный гиперпаратиреоз (ПГПТ) в сочетании с раком (как правило, медуллярным) щитовидной железы (ЩЖ) встречается при синдромах множественных эндокринных неоплазий. Сочетание немедуллярных карци-ном ЩЖ и ПГПТ отмечается у 3% пациентов. Доля папиллярного рака (ПР) ЩЖ достигает 87% от всех ее злокачествен-ных опухолей. Атипическая аденома (АА) околощитовидной железы (ОЩЖ) -это новообразование, в котором отсут-ствуют достоверные признаки инвазивного роста, но есть морфологические критерии, подозрительные в отношении их злокачественного потенциала. Распространенность АА ОЩЖ как причины ПГПТ составляет около 0,5-4%. АА ОЩЖ относятся к опухолям неопределенного злокачественного потенциала. Клиническое значение и отдаленные результаты, а также объем оперативного вмешательства и продолжительность наблюдения за пациентами с АА ОЩЖ из-за редкости опухоли и отсутствия стандартов диагностики данной патологии не определены. В настоящей статье авторы сообщают о двух случаях сочетания АА ОЩЖ и ПР ЩЖ у 63-летней женщины и 57-летнего мужчины. У одного из пациентов, в отличие от второго, были классические симптомы ПГПТ, в том числе тяжелая остео-дистрофия и нефропатия. Предоперационный уровень кальция составил 3,48 и 4,1 (2,12-2,6) мкмоль/л, паратиреоидно-го гормона -1300 и 1533 (15-65) пг/мл соответственно. В обоих случаях ультразвуковое исследование ЩЖ не выявило достоверно злокачественных новообразований. Рак ЩЖ был заподозрен только во время интраоперационной ревизии, в связи с чем пациентам была проведена тиреоидэктомия и удаление опухоли ОЩЖ. Гистологическое исследование выявило папиллярную микрокарциному ЩЖ (в первом случае одностороннюю, во втором -двустороннюю) и АА ОЩЖ. Большая осведомленность специалистов о сочетании ПРЩЖ с атипической аденомой ОЩЖ позволит расширить насто-роженность эндокринологов и хирургов, своевременно оценить возможную патологию ЩЖ у пациентов с ПГПТ, тем самым применить адекватный объем вмешательства в ходе одной операции. Клю че вые сло ва: папиллярный рак щитовидной железы, атипичная аденома околощитовидной железы, первичный гипер-паратиреоз.Most clinicians are well aware of the coexistence of medullary thyroid cancer and hyperparathyroidism in hereditary and sporadic multiple endocrine neoplasia syndromes. Тhe reported incidence of nonmedullary thyroid carcinoma in patients with primary hyperparathyroidism (pHPT) is only approximately 3%. Papillary thyroid carcinomas (PTC) is a malignant epithelial tumour. PTC represent up to 87% of all thyroid carcinomas. Atypical parathyroid adenoma (APA) are a subset of parathyroid neoplasms that exhibit some of the features of parathyroid carcinoma but lack unequivocal invasive growth. APA represents about 0.5-4% of cases of PHPT. As a group, they may be considered tumors of uncertain malignant potential. The clinical importance, and long-term outcomes as well as appropriate operative management and surveillance are not well defined for APA probably due to the overall low prevalence as well as the lack of a standard definition of APA. We rep...

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Negative Parafibromin Staining Predicts Malignant Behavior in Atypical Parathyroid Adenomas

Cited by 84 publications

References 22 publications

Clinicopathological correlates of hyperparathyroidism

Clinicopathological correlates of hyperparathyroidism

Diagnostic performance of parafibromin immunohistochemical staining for sporadic parathyroid carcinoma: a meta-analysis

Two cases synchronous atypical parathyroid adenomas and papillary thyroid carcinoma

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