Thyroid Nodule: Indeterminate Cytology and Lymph Nodes — EFSUMB MPUS 2026

What EFSUMB 2026 Changes in Practical Approach

EFSUMB Guidelines on Multiparametric Ultrasound Thyroid Nodule Evaluation: Part II, 2026 are dedicated to applied scenarios where grayscale ultrasound alone is often insufficient: indeterminate cytology Bethesda III/IV, multinodular goiter, suspicion of extrathyroidal spread, biopsy guidance, and neck lymph node staging. The document's logic is pragmatic: MPUS does not create a separate diagnosis but enhances the quality of clinical decision-making.

MPUS refers to the sequential integration of B-mode, color or power Doppler, elastography, and contrast-enhanced ultrasound (CEUS). The result should answer a specific question: where to puncture, are there signs of aggressive growth, which lymph node is most suspicious and suitable for verification.

Bethesda III/IV: Why Add MPUS

Indeterminate cytology is not a final diagnosis but an area of clinical uncertainty. For Bethesda III/IV, EFSUMB considers MPUS as a way to clarify the probability of malignancy and reduce the number of non-informative repeat interventions. It is important not to attempt to replace the cytological category with an ultrasound sign but to correlate the morphology, vascularity, stiffness, and enhancement of the nodule.

Practically, this means a repeat targeted examination of the nodule after obtaining cytology. The protocol should describe the capsule, contour, echogenicity, calcifications, height-to-width ratio, internal architecture, signs of capsular contact, or extension beyond the gland. Then Doppler, elastography, and, if indicated, CEUS are added.

Which Signs Increase Suspicion in Bethesda III/IV

In grayscale mode, signs traditionally associated with a high probability of thyroid cancer are concerning: hypoechogenicity, irregular or infiltrative contours, microcalcifications, vertical orientation, disruption of the gland capsule. In indeterminate cytology, these signs help justify a more active approach and select a site for repeat puncture or core biopsy.

Elastography adds information about the mechanical properties of the tissue. A stiff, heterogeneous nodule with focal dense areas requires attention, especially if these areas correspond to suspicious grayscale signs. EFSUMB emphasizes that a universal numerical stiffness threshold for all devices, techniques, and histological variants cannot be used; interpretation should be tied to the quality of the study and B-mode.

CEUS in Indeterminate Cytology

Contrast-enhanced ultrasound is useful when it is necessary to understand the viability of tissue within the nodule and select the optimal target for biopsy. Necrosis, cystic areas, hemorrhages, and gross degeneration can reduce the diagnostic value of puncture. CEUS helps distinguish avascular areas from perfused tissue and direct the needle to an area where there is a higher chance of obtaining representative material.

For risk assessment, reproducible patterns are important, not individual beautiful frames: heterogeneity of enhancement, perfusion defects, peripheral and internal contrast distribution, correspondence to suspicious areas in B-mode. The conclusion should be clinical: does CEUS affect the choice of puncture point, repeat biopsy, or surgical consultation.

Multinodular Goiter: Which Nodule to Puncture

In multinodular goiter, the error often arises from choosing the largest rather than the most suspicious nodule. EFSUMB guides prioritization based on ultrasound risk signs. MPUS is especially useful when several nodules appear similar in B-mode or when a large nodule has pronounced degeneration.

The algorithm is practical: first, a complete map of the gland is made, then each clinically significant nodule receives its own description, after which the target with the maximum combination of suspicious signs is selected. In CEUS, puncture of necrotic and cystic-degenerative areas should be avoided if the task is cytological or histological verification of solid tissue.

Extrathyroidal Invasion

Before surgery, ultrasound should assess not only the nodule itself but also its relationships with the thyroid capsule, trachea, muscles, vascular-nerve structures, and esophagus. Suspicion of extrathyroidal spread changes surgical planning, so it cannot be left as an indefinite phrase.

In the protocol, it is advisable to separate contact with the capsule, capsule deformation, and signs of its disruption with spread beyond the gland. Doppler and CEUS can help distinguish true tissue invasion from scar-fibrous changes or inflammatory contact, but the final interpretation remains complex.

Neck Lymph Nodes: What to Look For

Staging of lymph nodes in suspected thyroid cancer requires a systematic examination of the central and lateral neck compartments. It is not enough to write "no pathological lymph nodes detected" if it is not specified which zones were examined. For the surgeon, location is important: side, level or anatomical group, relation to vessels, trachea, muscles, and postoperative bed.

Classic suspicious signs include loss of echogenic hilum, round shape, heterogeneity, cystic transformation, microcalcifications, pathological peripheral or chaotic vascularization. For papillary cancer, microcalcifications and cystic changes are especially significant. CEUS can reveal heterogeneous enhancement, avascular necrotic zones, and helps select a viable area for puncture.

Table: MPUS Scenarios by EFSUMB 2026

Biopsy Guidance

The main principle is to puncture diagnostically significant tissue. In a thyroid nodule, this is a solid suspicious area, not a zone of necrosis, blood, or colloid. In a lymph node, it is an area with pathological structure and preserved tissue viability, not a completely cystic cavity unless it is the only accessible target.

MPUS is especially useful before repeat biopsy after an inconclusive result. Combining B-mode with CEUS allows pre-marking of the active zone, and elastography helps avoid technically difficult and uninformative areas of coarse fibrosis or calcification.

How to Formulate a Conclusion

The conclusion should not be a descriptive set of signs but an answer to a clinical question. For a nodule with Bethesda III/IV, it should indicate: do ultrasound signs match increased suspicion, is there a target for repeat biopsy, are there signs of extrathyroidal spread, and are suspicious lymph nodes identified.

For neck lymph nodes, it is necessary to indicate the side, anatomical zone, sizes without attempting to replace morphology with a single size, signs of suspicion, and the recommended target for verification. Such a protocol directly affects routing and reduces the risk of incomplete staging.