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Valutazione del grading nel carcinoma midollare tiroideo

Medullary Thyroid carcinoma: tumour grading

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L'Endocrinologo Aims and scope

Sommario

Il carcinoma midollare della tiroide è un tumore a origine neuroendocrina derivato dalle cellule della cresta neurale. Nonostante sia raro, è gravato da tassi di mortalità più alti se confrontato con i carcinomi differenziati dalla tiroide. Dalla prima descrizione istologica (1959) sono trascorsi 61 anni per introdurre il concetto di “grado tumorale” in questo tipo di neoplasia, mutuandolo dai corrispettivi tumori neuroendocrini gastrointestinali. La nuova classificazione basata sul grado tumorale proposta dal Sistema Internazionale del grading del carcinoma midollare (IMTCGS) suddivide i tumori in basso e alto grado a seconda della conta mitotica, dei livelli di KI67, e della presenza/assenza di necrosi. Tale classificazione si è dimostrata superiore rispetto al sistema della American Joint Committee on Cancer (AJCC-TNM) nel predire sia la sopravvivenza globale sia quella correlata alla malattia, come anche i tassi di recidiva. Passeremo in rassegna la descrizione delle tre classificazioni del grading proposte recentemente.

Abstract

Medullary thyroid carcinoma is a neuroendocrine tumour deriving from neural crest cells. Although rare, it has higher mortality rates when compared to differentiated thyroid carcinomas. Unfavourable prognostic factors are: advanced stage, elevated post-operative calcitonin levels, CEA, CA 19-9, doubling time calcitonin and CEA < 1 year, KI67 levels and RET918 somatic mutation. The upgrade of the new 2022 WHO classification defines medullary carcinoma according to tumour grading. In 2020, two independent study groups, one Australian and the other American, simultaneously published a work on tumor grading. The two studies differed in grade number, mitotic count, and KI 67 levels. Therefore to clarify the differences between the two studies an international consortium, by reviewing a 5-institution multicentre case series, has validated the ‘tumour grading’, adopting it from neuroendocrine tumours. In fact, the International Medullary Thyroid Carcinoma Grading System (IMTCGS) subdivides tumours into low- and high-grade according to mitotic count (< or ≥5 mitoses/2 mm2), KI67 levels (< or ≥5%), and the presence/absence of necrosis (also focal). This classification has been shown to be significantly superior to the AJCC-TNM (American Joint Committee on Cancer) system in predicting poorer overall survival (high-grade vs low-grade HR = 11.49, 95% confidence interval [CI] = 3.12–32.33, P < .001), disease-specific survival (high-grade vs low-grade HR = 8.49, 95% CI = 1.46–49.33, P = .017), distant metastasis–free survival (HR = 2.49, 95% CI = 1.18–5.26, P = .017), and locoregional recurrence–free survival (HR = 2.11, 95% CI = 1.07–4.19, P = .032). The significant prognostic ability of the IMTCGS was validated in analyses of cohorts from each of the five centers but also very recently by an other indipendent Italian group. The international consortium strongly recommends applying the new classification because it is easily obtained from the combination of anatomical-pathological data (mitotic count and necrosis also focal) and immunohistochemical evaluation (Ki 67 levels) that is quick, routine and low-cost. We will review the description of the 3 recently proposed grading classifications.

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Authors and Affiliations

  1. U.O.C. Endocrinologia, Prevenzione e Cura del Diabete, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant’Orsola, via Massarenti, 9, 40137, Bologna, Italia

    Andrea Repaci

  2. Anatomia Patologica, Dipartimento di Medicina Specialistica Diagnostica e Sperimentale (DIMES), Università di Bologna, Policlinico Sant’Orsola, via Massarenti, 9, 40137, Bologna, Italia

    Giovanni Tallini

  3. Laboratorio Interaziendale di Patologia Molecolare dei Tumori Solidi, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant’Orsola, via Massarenti, 9, 40137, Bologna, Italia

    Giovanni Tallini

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Correspondence to Andrea Repaci.

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Repaci, A., Tallini, G. Valutazione del grading nel carcinoma midollare tiroideo. L'Endocrinologo 24, 43–48 (2023). https://doi.org/10.1007/s40619-023-01228-3

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