A Case of Mediastinal Lymphoma that was Missed on EBUS-TBNA but Correctly Diagnosed after EBUS-TBCNB

ABBREVIATIONS USED IN THIS ARTICLE

EBUS-TBNA = Endobronchial ultrasound-guided transbronchial needle aspiration; EBUS-TBCNB = Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy; HRS = Hodgkin Reed-Sternberg.

INTRODUCTION

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has revolutionized the diagnostic process of various mediastinal pathologies. The pooled sensitivity and specificity of 95 and 100% respectively for diagnosis of mediastinal diseases are reported in one study.¹ Another systematic review has reported that EBUS-TBNB had excellent pooled specificity of 100% and a positive likelihood ratio of 5.1. The pooled sensitivity was 92%.^1,2 One major drawback of EBUS-TBNA is that it provides smaller sample sizes for the diagnosis and its diagnostic accuracy further reduces in lymphoproliferative disorders due to lower diagnostic sensitivity.³ Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy can yield larger samples for better histopathological characterization as well as further molecular profiling, which is the main issue with fine needle aspiration cytology (FNAC) samples sometimes. Now various studies have been reported that endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy (EBUS-TBCNB) is more sensitive to both malignant and benign diseases, and it is cost-effective and safe technique superior to EBUS-TBNA.^4–6

So, we are presenting a case where a middle-aged female underwent two EBUS-guided procedures, the first time EBUS-TBNA which was inconclusive, and the second time EBUS-TBNA combined with EBUS-TBCNB revealed classical Hodgkin lymphoma.

CASE PRESENTATION

A 51-year-old female patient without any comorbidity came into the outpatient department with a complaint of intermittent, high-grade fever for the last 6 months that often relieved on taking antipyretics. She also complained about intermittent dry coughs for the last 6 months. No diurnal variation in symptoms was present. The general as well as chest examinations were within normal limits, with bilaterally equal air entry and normal vesicular breath sounds on auscultation. No palpable lymphadenopathy was present. No abnormality was found on cardiovascular and other system examinations. Initial investigations revealed right hilar prominence on a chest radiograph with normal biochemical, microbiological, and pulmonary function parameters. The patient was further evaluated, and contrast-enhanced computed tomography of the thorax indicated the presence of multiple mediastinal lymph nodes, with the largest measuring 2.4 cm in short axis diameter at the right lower paratracheal station (4R). The patient was admitted and underwent EBUS-TBNA of the right lower paratracheal lymph node, which measured 20 mm on the EBUS (Olympus EBUS Bronchoscope). Procedure done under conscious sedation. Transbronchial needle aspiration core and bronchoalveolar lavage samples were obtained together with cytology samples and sent for investigation. No evidence of infection was found; cytology was inconclusive, but a TBNA core biopsy revealed chronic inflammation with an ill-defined granuloma without necrosis (Fig. 1).

The patient was evaluated for sarcoidosis, but all supportive parameters (Mantoux test, serum angiotensin-converting enzyme level, 24-hour urinary calcium level, ophthalmological examination, cardiovascular examination, as well as other biochemical parameters) were unremarkable. On the basis of persistent symptoms and findings of the core biopsy, the patient started on prednisolone at a dosage of 0.75 mg/kg/day. After 3 weeks, the patient again reported to the outpatient with similar complaints without any improvement on medications. Patient readmitted and planned for repeat EBUS-TBNA as well as EBUS-guided mediastinal cryonodal biopsy. A tract was made by a 19-gauge EBUS-TBNA needle under conscious sedation, and a 1.7 mm cryoprobe (ERBECRYO 2) was introduced via the same tract. Six TBNA passes were obtained for cytology, and two cryonodal biopsy samples were obtained under ultrasound guidance after an activation time of 4 seconds (Fig. 2).

Again, EBUS-TBNA cytology remains inconclusive, but the histopathology section shows a lymph node with an effaced architecture with polymorphs, lymphocytes, and a sprinkling of large polygonal cells. These cells show prominent nucleoli. Binucleate forms are also seen. Findings were suggestive of a lymphoproliferative disorder, either T-cell-rich B-cell lymphoma or Hodgkin’s lymphoma (Fig. 2).

A paraffin block for review and immunohistochemistry shows fragments of lymphoid tissue with total effacement of the lymph node architecture and replacement by a mixed infiltrate composed of small lymphocytes, histiocytes, and a few large, atypical single and multinucleated cells consistent with Hodgkin Reed-Sternberg (HRS) cells. Scattered mummified cells were also present. Tumor cells were positive for CD45, PAX-5 (heterogeneous pattern), MUM-1, CD15, CD30, CD68, and EBV while being negative for CK, CD3, and CD20. Ki67 proliferation index was 40%. The patient was diagnosed as a case of classical Hodgkin lymphoma and then discharged and referred to a medical oncology team for further management.

DISCUSSION

Although EBUS-TBNA has higher sensitivity and specificity in diagnosing mediastinal diseases, when it comes to lymphoma, its sensitivity decreases to a certain extent. It is because EBUS-TBNA provides smaller cytology or core biopsy samples sometimes, which may be insufficient for tissue characterization or molecular studies. Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy provides intact samples with greater volume, which results in higher diagnostic yields in uncommon tumors as well as in benign diseases.⁷ A randomized controlled trial on combined use of both EBUS-TBNA and EBUS-TBCNB also showed that this technique has a higher diagnostic yield in benign disorders, with a sensitivity of 94 vs 67%. This study also reported that this combined approach provided adequate samples for lymph node characterization as well as molecular and immune histochemical analysis of lung cancer with a similar complication profile to that of EBUS-TBNA.⁸

Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy can thus be used as an adjunct to TBNA in the diagnosis of cases that require histopathology specimens rather than cytology specimens, such as benign diseases, as well as in suspected cases of difficult-to-diagnose malignant diseases, such as lymphoma.

In our case, EBUS-TBNA came inconclusive two times, and the diagnosis of classical Hodgkin lymphoma was made only after EBUS-TBCNB. Although in previous literature, bronchoscopists had introduced a 1.1 mm cryoprobe via a tract formed by an EBUS-TBNA needle, we managed to introduce a 1.7 mm cryoprobe after creating a tract by six passes of a 19 gauge needle. The procedure is performed under conscious sedation, and no untoward complications were seen.

Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy is a relatively safe and well-tolerated procedure that is usually associated with minor adverse events. These may include bleeding, pneumomediastinum, pneumothorax, and spread of infection into the mediastinum as well as adverse events related with EBUS.⁹

The freezing time of the cryoprobe in our study was 4 seconds, and two biopsy samples were obtained. However, previous literature showed various freezing times and techniques for tract formation according to the diameters of cryoprobes.^7,10,11 Thus, future research is needed for optimal technical aspects such as tract-creating tools, freezing time, and the number of passes for cryonodal biopsy of mediastinal lymph nodes.

CONCLUSION

As in our study, we were able to make a diagnosis only after obtaining the sample by cryonodal biopsy without any complications. Endobronchial ultrasound-guided transbronchial mediastinal cryonodal biopsy is a safe and effective procedure that can be used in the successful diagnosis of mediastinal pathologies where EBUS-TBNA remained inconclusive, or it may be used as a combined procedure with EBUS-TBNA in cases of diagnostic uncertainty.

ORCID

Deependra K Rai https://orcid.org/0000-0001-9090-8124

Niraj K Singh https://orcid.org/0009-0008-7157-6185

Vinay V https://orcid.org/0000-0003-1691-2111

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