Prevalence and Malignant Involvement of Calcified Intrathoracic Lymph Nodes in Patients Undergoing Endosonography

The presence of calcifications, which is a relatively common feature in intrathoracic lymph nodes, typically contributes to confer them a heterogeneous aspect during endosonographic B-mode examination, but a possible association between calcifications and metastatic involvement has never been systematically evaluated. The most likely reason why this possible association has been overlooked up to now is that the presence of calcifications in intrathoracic lymph nodes has long been thought to be the consequence of the prior involvement from granulomatous diseases (i.e., tuberculosis or sarcoidosis), and as such has been considered a sign of benignity. However, the presence of lymph node calcifications at ultrasound examination is a known predictor of lymph node metastasis in patients with some specific tumours, such as the papillary thyroid carcinoma or the squamous cell carcinoma of head or neck. Furthermore, recent radiological-pathological studies have shown that metastatic foci from lung cancer are observed in up to 19% calcified mediastinal lymph nodes identified at CT in surgical candidates. Finally, a recently published EBUS study has reported, for the first time, a very strong association between a very specific pattern of mediastinal lymph node calcification, known as "starry sky sign", and metastasis from pulmonary, colonic and breast adenocarcinoma. Interestingly, the starry sky sign is characterized by the presence of few to countless dot-like calcifications which are too small to be seen at CT and can be identified only during EBUS B-mode examination.

To the best of our knowledge, no studies have been carried out to assess the correlation between the presence and the ultrasound pattern of lymph node calcifications and lymph node metastasis from lung cancer or other intrathoracic malignancies.

Inclusion criteria

• Age >18 years at the time of the procedure
• Known or suspected lung cancer or other intrathoracic malignancy based on imaging (CT and/or PET/CT)
• Endosonography (EBUS and/or EUS) indicated for intrathoracic lymph node assessment/sampling according to national and international guidelines: 1) enlarged (> 1 cm on its short axis at CT) and/or PET positive lymph node; and/or 2) conditions at risk for occult mediastinal metastases, such as: i) central primary tumor; ii) primary tumor > 3 cm; iii) PET negative primary tumor; iv) ipsilateral hilar metastasis (cN1 status).

Exclusion criteria

• Inability or unwillingness to consent
• Compromised upper airway (i.e., concomitant head and neck cancer with upper airway obstruction; critical central airway obstruction from any cause)
• Contraindication for temporary interruption of the use of antiplatelet (excluded aspirin) or anticoagulant drugs
• American Society of Anesthesiologists grade 4