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The Safety of Cryobiopsy in Diagnosing Carcinoid Tumors

Boyd, Michael MD; Sahebazamani, Mitra MD; Ie, Susanti MD; Rubio, Edmundo MD

Journal of Bronchology & Interventional Pulmonology: July 2014 - Volume 21 - Issue 3 - p 234–236
doi: 10.1097/LBR.0000000000000079
Case Reports

Background: Cryotherapy probes have recently found an expanding role as a routine diagnostic instrument to sample endobronchial pathology. However, its overall safety and efficacy in biopsying carcinoid tumors has not been clearly established. Carcinoid tumors are more vascular and may be prone to more bleeding when biopsied by a cryoprobe.

Methods: Review of 5 cases that underwent cryoprobe biopsies for carcinoid tumors was carried out.

Results: Cryobiopsy was successful to diagnose all suspected cases of endobronchial carcinoid tumors. The samples obtained were of good quality and devoid of crush artifact. There was no associated significant bleeding or other complications.

Conclusions: Cryotherapy probe biopsy should be considered a safe and effective approach to diagnose carcinoid tumors.

Section of Pulmonary, Critical Care, Environmental, and Sleep Medicine, Carilion Clinic, Virginia Tech Carilion School of Medicine, Roanoke, VA

Disclosure: There is no conflict of interest or other disclosures.

Reprints: Michael Boyd, MD, Section of Pulmonary, Critical Care, Environmental, and Sleep Medicine, Carilion Clinic, Virginia Tech Carilion School of Medicine, 1906 Belleview Ave, Roanoke, VA 24014 (e-mail:

Received July 5, 2013

Accepted April 22, 2014

Recent reports have demonstrated that cryoprobe biopsy (CB) of endobronchial lesions offers a higher diagnostic yield than traditional forceps biopsy (FB). Larger sample size, both from benign and malignant lesions, has been credited for this improvement.1–3 With regard to safety, severe bleeding associated with CB was found to be comparable to FB (18.2% vs. 17.8%).1 On the basis of above studies it seems reasonable to conclude that CB would be the preferred method to diagnose any endobronchial lesion. However, in the presence of more vascular lesions, such as carcinoid, with a previously reported bleeding risk as high as 26%, the safety and efficacy of CB has not been well documented.4 It is plausible but uncertain whether the additional vasoconstrictive effect of “cold” biopsy may actually decrease the risk of bleeding in such tumors. In an attempt to answer this question, we present this case series of 5 carcinoid tumors diagnosed by the routine use of CB with a report of its overall safety and efficacy.

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Case 1

A 65-year-old woman with a history of cigarette smoking and chronic obstructive pulmonary disease presented with recurrent pneumonia and hemoptysis. Three years earlier, she had been diagnosed with a right superior segment endobronchial carcinoid tumor. Because of her advanced lung disease, she was not deemed as a surgical candidate. Subsequently, she underwent bronchoscopic debulking of the endobronchial tumor with the use of argon plasma coagulation. After 2 years, she developed recurrent symptoms and as a result presented to our pulmonary clinic. Chest computed tomography (CT) revealed an endobronchial lesion at the level of the bronchus intermedius. Flexible bronchoscopy with cryobiopsies confirmed the findings of recurrent carcinoid tumor (Figs. 1, 2).





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Case 2

A 48-year-old nonsmoker man with history of chronic back pain presented for the evaluation of significant weight loss and diarrhea. He also reported a recent history of productive cough and fever associated with left-sided chest pain. A chest roentgenogram (CXR) revealed a left pleural effusion. Subsequent chest CT showed a left hydropneumothorax with consolidation in the left lower lobe and inferior segment of the lingular lobe. The patient underwent flexible bronchoscopy revealing an endobronchial lesion in the left upper lobe, which appeared to be hypervascular. Transbronchial forceps biopsies and cryobiopsies of the lesion were performed, which confirmed the diagnosis of carcinoid tumor.

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Case 3

An 82-year-old asymptomatic nonsmoking woman with an incidental radiographic finding of a left lower lobe lung mass underwent flexible bronchoscopy with endobronchial biopsy at an outlying institution. After one biopsy, the procedure was halted because of subjectively reported “bleeding” from the left lower lobe lesion. The pathology was suspicious for an atypical carcinoid verses small cell carcinoma. The patient was subsequently transferred to our facility for a repeat biopsy. She underwent endobronchial forceps biopsies and cryobiopsies of the left lower lobe lesion, which were both consistent with a diagnosis of carcinoid tumor.

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Case 4

A 37-year-old man with history of tobacco abuse and obstructive sleep apnea underwent CXR for evaluation of left-sided focal wheezing. CXR showed a lingular infiltrate. Chest CT revealed a filling defect at the left upper lobe bronchus associated with air trapping and a lingular infiltrate. Consequently, he underwent a bronchoscopy with cryobiopsies of a left upper lobe lesion, which was consistent with carcinoid tumor.

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Case 5

A 37-year-old man with a history of a dry cough and positional wheezing underwent chest CT, which demonstrated a left hilar mass and left lung atelectasis. The patient underwent a flexible bronchoscopy, which revealed a pearly shiny endobronchial tumor in the left mainstem bronchus. Forceps biopsies and cryobiopsies were obtained. The final pathology report was consistent with carcinoid tumor. Two months later, the patient was scheduled for a lobar bronchial sleeve resection; however, a repeat bronchoscopy did not reveal any significant residual tumor. The procedure was therefore aborted and the patient has since been followed up with a repeat surveillance bronchoscopy with no tumor recurrence being observed.

It is noted that all cases were successfully biopsied with no bleeding or any other reported complications and all samples demonstrated good preservation of the histologic architecture, without crush artifact.

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Although there appears to be sufficient data to ascertain the superiority of CB when approaching endobronchial lesions, irrespective of their nature, its use is still not widespread. Its safety has not been clearly established when dealing with more vascular lesions, specifically carcinoid tumors. Most of the studies examining CB were performed by a few operators at various medical centers in Germany and Turkey, with a reported risk of bleeding ranging from 5.1% to 36.6%. Only a few patients who underwent CB were diagnosed with carcinoid; however, these studies did not provide a detailed analysis of their associated risk of bleeding.1–3 The early literature has suggested that bronchial carcinoids were more likely to bleed when biopsied.4 Despite more contemporary reports to the contrary, many bronchoscopists remain reluctant to biopsy them.5,6 Therefore, a better understanding of the safety of CB in carcinoid lesions is important.

Cryotechnology has been used for years for both recanalization of endobronchial carcinoid, as well as to consolidate therapy of bronchoscopically ablated carcinoid lesions.7,8 Bleeding associated with these interventions has not been clearly documented. We maintain that CB should also be considered when trying to diagnose endobronchial carcinoid lesions. It is important to point out that although the usage of a cryoprobe for therapeutic versus diagnostic purposes may have similarities, these interventions are not identical and may carry different risks. For instance, in “consolidative therapy,” the base of the bronchoscopically resected carcinoid tumor is further treated to prevent possible submucosal tumor involvement from regrowing. To accomplish this, tissue is allowed to freeze and then thawed repeatedly to cause delayed injury but without attempting immediate tissue removal; therefore, bleeding risk should be minimal. The use of a cryoprobe to debulk tumor requires removal of the probe with adequate freezing time to allow immediate removal of sufficient tumor to reestablish airway patency. The risk of bleeding under these circumstances should be higher. Although the ideal freeze duration for CB has not been established, it should be sufficient to allow an adequate amount of tissue adherence to the probe (our bronchoscopist tend to freeze for at least 3 seconds or until the first evidence of visible freezing), but limited as not to result in a large volume of tissue removal, as with tumor bebulking procedures. Without knowledge of the bleeding risk associated with CB of carcinoid tumors, it is understandable that some practitioners may still doubt its safety. The cases we presented should provide greater assurance that CB of carcinoid tumors can be carried out safely.

On the basis of our small series and review of the literature, CB may be as equally safe as forceps biopsy. As such, CB could be considered when diagnosing carcinoid lesions. It appears that even a short period of freezing may allow for CB to induce enough vasoconstriction, which could help minimize the bleeding risk. Compared with forceps biopsies, CB obtains larger and better preserved samples, which are devoid of the crush artifact commonly observed with traditional forceps biopsies.

In conclusion, we suggest that pulmonologists with access and experience with cryotechnology should consider its use to sample endobronchial carcinoid. The cases presented supports that CB is a safe and effective means to biopsy carcinoid lesions, carrying a minimal bleeding risk. In addition, CB-obtained tissue samples seem to be of equal or better quality than those obtained by forceps.

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1. Hetzel J, Eberhardt R, Herth F, et al..Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.Eur Respir J.2012;39:685–690.
2. Schumann C, Hetzel J, Babiak A, et al..Cryoprobe biopsy increases the diagnostic yield in endobronchial tumor lesions.J Thorac Cardiovasc Surg.2010;140:417–421.
3. Aktas Z, Gunay E, Hoca N, et al..Endobronchial cryobiopsy or forceps biopsy for lung cancer diagnosis.Ann Thorac Med.2010;5:242–246.
4. Todd TR, Cooper JD, Weissberg D, et al..Bronchial carcinoid tumors: twenty years’ experience.J Thorac Cardiovasc Surg.1980;79:532–536.
5. Hurt R, Bates M.Carcinoid tumours of the bronchus: a 33 year experience.Thorax.1984;39:617–623.
6. Fink G, Krelbaum T, Yellin A, et al..Pulmonary carcinoid: presentation, diagnosis and outcome in 142 cases in Israel and review of 640 cases from the literature.Chest.2001;119:1647–1651.
7. Schumann C, Hetzel M, Babiak A, et al..Endobronchial tumor debulking with a flexible cryoprobe for immediate treatment of malignant stenosis.J Thorac Cardiovasc Surg.2010;139:997–1000.
8. Bertoletti L, Elleuch R, Kaczmarek D, et al..Bronchoscopic cryotherapy treatment of isolated endoluminal typical carcinoid tumor.Chest.2006;130:1405–1411.

bronchoscopy; cryobiopsy; carcinoid

© 2014 by Lippincott Williams & Wilkins.