Is desmoplastic stromal reaction useful to modulate lymph node dissection in sporadic medullary thyroid carcinoma?

Background: Guiding surgical extent of sporadic medullary thyroid carcinoma on the basis of solely basal calcitonin levels has been questioned because of the potential postoperative complications and uncertain oncologic benefit. Desmoplastic stromal reaction has re-emerged as a promising marker of nodal metastases. We aimed to analyze the value of desmoplastic stromal reaction in tailoring surgical strategy as well as revisit the role of known predictive factors such as basal calcitonin.

Methods: We retrospectively analyzed operations for medullary thyroid carcinoma between 1997 and 2022, including patients whose specimens were available for desmoplastic stromal reaction evaluation (2018-2022). Risk factors for nodal metastases were assessed using univariable and multivariable analyses. Predictors of nodal metastases and potential basal calcitonin thresholds with optimal sensitivity, specificity, positive predictive value, and negative predictive value were evaluated.

Results: Among 246 medullary thyroid carcinomas, 139 sporadic unifocal cases were eligible and 57 patients were retrospectively evaluated for desmoplastic stromal reaction. After univariable analysis, desmoplastic stromal reaction positivity (P = .002), basal calcitonin >113 pg/mL (P = .004), and lesion size >20 mm (P = .042) were significantly associated with nodal metastases. After backward stepwise logistic regression, desmoplastic stromal reaction positivity and basal calcitonin >113 pg/mL resulted in being independent risk factors for nodal metastases. Desmoplastic stromal reaction positivity showed a 100% sensitivity, an 82.5% specificity, an 18.4% positive predictive value, and a 100% negative predictive value for nodal metastases.

Conclusion: Our results suggest that for minimal desmoplastic stromal reaction- disease, prophylactic lateral neck dissection could be avoided. In contrast, lateral neck dissection should be strongly considered in cases of advanced disease (desmoplastic stromal reaction positivity and basal calcitonin >500 pg/mL). In case of desmoplastic stromal reaction positivity and bCT <500 pg/mL, the extension of lymph node dissection should be tailored to patient and lesion features.