A retrospective study of the clinical and laboratory predictors and morphological characteristics of the parathyroid carcinoma

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Abstract

Background: there are no specific markers of the parathyroid carcinoma (PC) therefore, the development of algorithms for identifying high-risk patients is an urgent task.

Aims: to determine the clinical and laboratory predictors of PC and to identify the factors of a poor prognosis.

Materials and methods: A multicenter retrospective study included 242 patients with primary hyperparathyroidism (PHPT) who were divided into groups: 162 with adenomas, 30 with аtypical adenomas (АА) and 50 patients with PC. Data collection and analysis was carried out from 2017 to 2020. The primary goal— assessment of the possibility of PС using preoperative laboratory and instrumental data. The group of PC was divided into subgroups: the patients in recurrences (n=17) and remission (n=33). The level of the total calcium, albumin, alkaline phosphatase (ALP), ionized calcium (Ca ++) in the blood were determined on the automatic biochemical analyzer; the level of parathyroid hormone (PTH) by electrochemoluminescent analyzer. The size of the PG determined by the ellipse formula: V (cm3) = (A × B × C) × 0.49. Statistical analysis was performed with Statistica 13 and SPSS software packages. For multiple comparisons, the Bonferroni correction was applied.

Results: the group of patients with increased risk of PC include persons with increased level of PTH >443 pg/ml, Ca++ >1.5 mmol/l, total calcium >3.2 mmol/l, ALP >176 IU/L, V of tumors >2.6 cm3, largest size >22.5 mm (p <0,001). Heterogeneous structure is more typical to PC compared to the АА (p = 0,004 and р = 0,011), the same applies to indefinite contour (р = 0,001 и р = 0,011). Pathological mitosis is a prognostically unfavorable factor of recurrence of PC (р=0,007).

Conclusions: the patients with PC and AA are characterized with more aggressive course of PHPT compared to the group of adenomas.

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About the authors

Julia A. Krupinova

Endocrinology Research Centre

Author for correspondence.
Email: j.krupinova@gmail.com
ORCID iD: 0000-0001-7963-5022
SPIN-code: 6279-8247

MD, research associate

Russian Federation, Moscow

Iya A. Voronkova

Endocrinology Research Centre; Moscow Regional Research and Clinical Institute

Email: iya-v@yandex.ru
ORCID iD: 0000-0001-6687-3240
SPIN-code: 9685-1371

MD, PhD

Russian Federation, Moscow; Moscow

Alina R. Ajnetdinova

Endocrinology Research Centre

Email: 9803005@mail.com
ORCID iD: 0000-0001-6935-3187
SPIN-code: 9617-7460

Doctor-Statistician

Russian Federation, Moscow

Aleksandr Y. Abrosimov

Endocrinology Research Centre

Email: nikitarusskikh@mail.ru
ORCID iD: 0000-0001-8284-9996
SPIN-code: 4089-9502

MD, PhD, Professor

Russian Federation, Moscow

Irina V. Kryukova

Moscow Regional Research and Clinical Institute

Email: kiv200877@yandex.ru
ORCID iD: 0000-0002-7876-5105
SPIN-code: 7669-3010

MD, PhD, Assistant Professor

Russian Federation, Moscow

Stanislav V. Lukyanov

Rostov State Medical University

Email: svluk@rambler.ru
ORCID iD: 0000-0002-3317-0108
SPIN-code: 4181-8431

MD, PhD, Assistant Professor

Russian Federation, Rostov-on-Don

Julia S. Veretennikova

Endocrinology Research Centre

Email: veretennikova-j@mail.ru
ORCID iD: 0000-0001-8849-9595
SPIN-code: 7410-9041

Clinical Resident

Russian Federation, Moscow

Larisa K. Tevosyan

Moscow Regional Research and Clinical Institute

Email: tlh_moscou@mail.ru
ORCID iD: 0000-0002-8954-1633
SPIN-code: 7376-4180

MD

Russian Federation, Moscow

Galina A. Melnichenko

Endocrinology Research Centre

Email: teofrast2000@mail.ru
ORCID iD: 0000-0002-5634-7877
SPIN-code: 8615-0038

MD, PhD, Professor, Academician of the RAS

Russian Federation, Moscow

Natalia G. Mokrysheva

Endocrinology Research Centre

Email: parathyroid.enc@gmail.com
ORCID iD: 0000-0002-9717-9742
SPIN-code: 5624-3875

MD, PhD, Professor, Corresponding Member of the RAS

Russian Federation, Moscow

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Supplementary files

Supplementary Files
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1. Figure 4. Vascular invasion of the capsule and surrounding soft tissue

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2. Figure 1. Parathyroid carcinomas from the Chief cells with different degrees of cytonuclear atypia

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3. Fig. 1. Study design

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4. Fig. 2. ROC-analysis of laboratory and instrumental predictors of differential diagnosis of PTG masses: A - ROC- iPTG analysis, AUC = 0.884 (95% CI 0.821–0.948); B - ROC analysis of Ca ++, AUC = 0.840 (95% CI 0.756–0.924); B - ROC analysis corrected calcium, AUC = 0.835 (95% CI 0.759-0.910); D - ROC analysis of alkaline phosphatase, AUC = 0.835 (95% CI 0.759-0.910); D - ROC analysis of the largest size of education by ultrasound, AUC = 0.832 (95% CI 0.766–0.899); E - ROC analysis volume of education by ultrasound, AUC = 0.877 (95% CI 0.812-0.941)

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5. Fig. 3. Cancer of the thyroid gland: A - wide fibrous cords; B - invasion of the tumor capsule; B - increased mitotic activity of PTG carcinoma (3 mitoses in 1 RPZ); D - germination of PTG cancer (1) into the tissue of the thyroid gland (2)

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