Just as the technology, imaging and sampling modalities available to clinicians have expanded, the Pathologist's diagnostic armament including new molecular techniques, novel antibodies in immunocytochemical staining, and specimen processing has expanded dramatically over the past decade as well.
EUS-FNA is a minimally invasive technique well suited for cytologic and immunohistochemical diagnosis of mediastinal lesions. Among the 116 patients in our study, the sensitivity, specificity, and accuracy of the final FNA read to predict final LN diagnosis of malignancy were 100%. Other smaller studies[10
] have shown sensitivity and accuracy of EUS-FNA to be about 69% and 75%, respectively. In that study involving 20 patients, surgical diagnostic procedures were precluded in 60% of the patients. Similar results are mirrored in larger studies[11
] in the context of patients with previous extrathoracic malignancy and suspected mediastinal metastases, where EUS-FNA consistently demonstrates high sensitivity (86%) and accuracy (91%).[11
] Negative predictive value of EUS-FNA for mediastinal staging was found to be 72% by the some authors.
The role of EUS-FNA even in low-volume EUS centers (<50 mediastinal EUS-FNA/endoscopist/year) has been examined by a recent European study[12
] involving 213 patients where the clinical impact of EUS-FNA was evaluated by using the classification put forward by Chen and Eloubeidi.[13
] The study concluded that EUS-FNA had a positive impact on clinical management in 178 of 213 (84%) procedures, whereas only in 16 of 213 (8%) procedures, clinical management was considered to have been negatively affected by the cytological results by providing false-negative or inconclusive cytology. This overall positive effect of cost-reduction was also quantified by calculating the total cost of the actual diagnostic workup vs the total cost of the alternative diagnostic workup, including the costs of all the components of the diagnostic procedures (In the alternative diagnostic workup, for example, mediastinoscopy instead of EUS-FNA would have been performed in 143 patients with an estimated complication risk of 2%).
It is not surprising then that by performing 213 EUS-FNAs, €100 593 (or ~133 000) were saved[12
] (not including the cost of surgery for non-diagnostic alternative interventions). The impact on cost reduction has been corroborated by other authors as well. Eloubeidi et al
] showed an even higher average cost reduction of $11 033 per patient by using EUS-FNA instead of mediastinoscopy as the primary staging tool in patients with non-small cell lung carcinoma. Combining EUS-FNA with PET has also been shown to reduce staging costs by 40% by obviating surgical staging.[15
Traditionally, the use of EUS-FNA for ML has been in the context of lung cancer staging where it has clearly been shown to reduce the incidence of futile thoracotomies (especially where the stage of the disease is more advanced than expected preoperatively) from 25% to 9%.[16
] It can also facilitate a more thorough examination of not only the mediastinal nodal stations but also the adrenals[17
] and other infradiaphragmatic sites of potential spread. Although conventionally mediastinoscopy was regarded as the “gold-standard” for mediastinal staging, it is limited in sampling less accessible areas such as aortopulmonary, retrotracheal, posterior carinal, or inferior mediastinal lymph nodes. Also, with the lower complication rates following EUS-FNA in various cohorts,[11
] EUS is now indicated as a minimally invasive alternative for surgical staging in recent lung cancer staging guidelines.[20
Characteristic immunostaining and cytomorphological features help in diagnosing less common tumors in locations other the mediastinum sampled with EUS-FNA (such as the solid-pseudopapillary tumors of the pancreas with immunostaining for Neuron-specific enolase,α1
-antitrypsin, and α1
] or either CD117 immunostaining or high-resolution amplicon melting analysis for CD 117/PDGFR mutations for Gastrointestinal stromal tumors[22
EUS with FNA provides a viable approach to the diagnosis and staging of tumors in the head and neck region as well, when there is a suggestion of esophageal invasion on CT or MRI, or enlarged mediastinal lymph nodes.[24
] Additionally, for example, parathyroid hormone concentration measurement in the aspirated material in cases of suspected mediastinal parathyroid adenomas may make EUS-FNA a useful adjunct in diagnosing mediastinal parathyroid adenomas.[25
Even for hepatic lesions, early experience[26
] suggests that EUS-FNA is comparable with CT-FNA in terms of diagnostic utility. EUS FNA should be considered especially if the lesion is in the hilum and left lobe of the liver or the proximal biliary tract. The gallbladder, extrahepatic biliary system, and perihilar lymph nodes are readily accessible as well.
Our study outlines the role of EUS-FNA in diagnosing the non-malignant, inflammatory, or infectious causes of ML such as sarcoidosis, fungal infections, especially when special features help direct onsite evaluation toward the correct diagnosis. In one study,[28
] sensitivity of EUS in detecting granulomas in patients with sarcoidosis causing ML was 87% (with cell-block analysis added to conventional cytological evaluation), with the optimal yield for granuloma detection reached with four needle passes. These non-malignant conditions are particularly suited for diagnosis through EUS-FNA when characteristic pathologic findings (such as asteroid bodies or epitheloid granulomas) are seen.
Working in association with an experienced cytopathologist aware of artifacts inherent in EUS-FNA sampling can minimize diagnostic errors.[26
] This is especially relevant with lesions that have characteristic histopathologic and immunophenotypic features.[29
] With some of these lesions where ancillary immunophenotyping may be key to diagnosis, EUS-FNA has been shown to be superior to CT-guided FNA.[32
In our study, the history of prior malignancy was associated with detection of malignant lymph nodes in the mediastinum. From our observation and interactions with our pathology group, we note that it is of paramount importance to discuss the clinical history with our colleagues in cytopathology at the time of tissue collection, so that adequate material can be obtained at the time of onsite interpretation for further ancillary studies such as immunostains, flow cytometry, and culture.
Limitations of our study included the retrospective evaluation of data which were prospectively collected. In addition, the majority of the LNs of our cohort were located at level 7, which is most likely explained by referral bias regarding the utility of EUS-FNA in this subset of patients. The other limitation is the absence of surgery and 6-month follow-up in a small proportion of our patients. We used a compound reference standard similar to other investigations in the field.
With our study, we describe the unique experience in evaluation of ML at our institution and reiterate the expanding and central role of EUS-FNA in diagnosing mediastinal pathology.