Bronchoscopic Transbronchial Cryobiopsy Diagnosis of Recurrent Diffuse Large B-Cell Lymphoma in the Lung: A Promising New Tool?

To the Editor:

The yield from conventional transbronchial biopsy of the lung for pulmonary lymphoma is often hampered by small samples afflicted by crush artefacts. Consequently, surgical lung biopsy, the only alternative available until recently, is often required to establish a diagnosis. Many patients are comorbid and unable to tolerate such a surgical procedure which itself is associated with significant risks. Endobronchial cryotherapy has been used for many years with success due to its ability to remove much larger specimens compared with conventional forceps. Its use ranges from sampling endobronchial lesions to recanalization of airway lumen from lung cancers.1 In addition to providing large specimens, the ease of handling the cryoprobe and relatively low set up cost has led to cryotherapy being investigated as a means of sampling lung parenchyma. Transbronchial cryobiopsy (cryo-TBB) has been examined as a diagnostic tool for diffuse or interstitial lung disease2 as well as in after lung transplant surveillance.3 In these studies, the size of specimens retrieved by cryoprobe were significantly larger than those obtained by conventional forceps. Samples were generally between 5 and 7 mm in maximum diameter, contained less crushed artefacts and greater preserved architecture. Adverse effect profiles from cryo-TBB appear slightly higher compared with conventional forcep transbronchial biopsy in terms of bleeding and pneumothorax, but without any increase in mortality risk. The use of cryo-TBB in these lung conditions may become more widespread in the future as the community develops experience and provide evidence of its efficacy.

To our knowledge, there are no large studies examining the use of cryo-TBB in pulmonary lymphoma. Ours is the second case reporting on the successful use of cryo-TBB as a diagnostic tool for diffuse large B-cell lymphoma (DLBCL) presenting in pulmonary parenchyma. The other case report illustrates the use of cryo-TBB in diagnosing primary pulmonary DLBCL.4 Our case has 2 unique features in that the patient presented as a late relapse and her presentation was isolated to lung parenchyma with pleural effusion, without lymphadenopathy. Relapse from treated DLBCL after 5 years or later is very rare with a described rate of around 3.6%.5 Furthermore, isolated pulmonary parenchymal DLBCL is uncommon for both first presentation and recurrence, prompting the need for a definitive diagnosis.

In our patient, flexible bronchoscopy with transbronchial forcep and cryobiopsies were performed in the operating theater. Anesthesia was induced and maintained with propofol, dexmedetomidine, and alfentanil and the patient was breathing spontaneously throughout the procedure. She was intubated with a laryngeal airway mask and an endobronchial blocker was placed prophylactically in the bronchus intermedius. Radial endobronchial ultrasound with guide sheath was performed with the 1.8 mm radial probe (UM-S20-17S Olympus) to aid location of abnormal lung parenchyma. Fluoroscopy was used to confirm the position of the probe within the lateral segment of the right middle lobe (Fig. 1) at least 2 cm away from the lung edge. The following sampling methods were performed sequentially: cytology brush, forcep, needle aspiration, and 2 cryobiopsies (1.9 mm, ERBE, Germany). The cryogen gas used was carbon dioxide and freezing time was 3 seconds. The cryoprobe and bronchoscope were removed en bloc after each cryobiopsy. A second bronchoscope was inserted immediately to inspect for bleeding distal to the endobronchial blocker. No significant bleeding occurred after both biopsies, and a chest x-ray performed an hour after the procedure confirmed no pneumothorax had occurred.

FIGURE 1

Fluoroscopy image of cryoprobe extending into right middle lobe and endobronchial blocker within bronchus intermedius.

Specimens from the brush, needle aspirate, and forcep had significant crush artefacts and contained atypical lymphoid cells. The cryobiopsy specimens measured 6×4 and 6×3 mm. One contained inflammed lung parenchyma without evidence of neoplasia, while the other showed lung parenchyma infiltrated by singly distributed large, atypical lymphoid cells showing pleomorphic and irregular nuclei with prominent nucleoli. Immunohistochemistry stains confirmed these as abnormal B cell infiltrates (positive labelling for CD20, CD79a, BCL6, CD10), which have a Ki67 proliferative index of 80% to 90%. Comparison with the original inguinal lymph node histology found similar features, thereby confirming recurrence of DLBCL of the lung.

In our patient, the cryo-TBB specimen was the only diagnostic specimen, while the other results were merely suggestive. Without the cryobiopsy specimen, a definitive diagnosis of DLBCL recurrence would not have been possible. This case highlights the potential value of transbronchial cryobiopsy as a diagnostic modality for pulmonary parenchymal lymphoma. Further larger case studies are required to establish the efficacy and safety of cryo-TBB in this setting, but cryo-TBB could be considered in patients presenting with lung parenchymal abnormalities where lymphoma is suspected, particularly if preexisting comorbidities prohibit surgical lung biopsy.