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The Intranodal Presence of Coexisting Granulomatous Inflammation and Carcinoma During Transbronchial Needle Aspiration of Intrathoracic Lymphadenopathy

Gilbert, Christopher R. DO, MS; Abendroth, Catherine MD; Yarmus, Lonny B. DO

Journal of Bronchology & Interventional Pulmonology: January 2017 - Volume 24 - Issue 1 - p 80–83
doi: 10.1097/LBR.0000000000000218
Case Reports

The presence of intrathoracic lymphadenopathy in patients with suspected malignancy remains concerning, often prompting further evaluation with tissue sampling. The presence of nodal granulomatous inflammation in patients with underlying malignancy is well reported. However, review of 3 recent large trials of endobronchial ultrasound-guided transbronchial needle aspiration in patients with granulomatous inflammation and malignancy did not identify the presence of coexisting, intranodal malignancy, and granulomatous inflammation, rather these diagnoses remained nodally exclusive. We present a case of coexisting granulomatous inflammation and metastatic carcinoma within the same lymph node aspirates, reviewing the potential diagnostic pitfalls and implications of this rare occurrence.

*Swedish Cancer Institute/Swedish Medical Center, Division of Thoracic Surgery and Interventional Pulmonology, Seattle, WA

Department of Pathology, Penn State College of Medicine-Milton S. Hershey Medical Center, Hershey, PA

The Johns Hopkins University School of Medicine, Division of Pulmonary and Critical Care Medicine, and Interventional Pulmonology, Baltimore, MD

C.R.G.: guarantor of the manuscript, taking responsibility for the integrity of the work as a whole, from inception to published article. C.R.G., C.A., L.Y.: contributed to data collection, data review, manuscript writing, and review.

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

Reprints: Christopher R. Gilbert, DO, MS, Swedish Cancer Institute/Swedish Medical Center, Division of Thoracic Surgery and Interventional Pulmonology, 1101 Madison St., Suite 900, Seattle, WA 98117 (e-mail: christopher.gilbert@swedish.org).

Received March 18, 2015

Accepted September 8, 2015

The presence of intrathoracic lymphadenopathy in a patient with a prior or suspected malignancy remains a concerning discovery. Although malignant dissemination is often suspected, other etiologies remain possible and therefore further evaluation with tissue sampling is warranted.

Granulomatous inflammation (or sarcoid-like reaction) has been previously described within lymph nodes aspirates of patients with underlying malignancy. The most common occurrence appears in association with tumors such as lymphoma, gastric,1 testicular,2 breast,1,3 and lung cancer.3 The documented incidence of granulomatous inflammation in cytologic specimens obtained via endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is 4% to 12%.4–7 Interestingly, in the 3 largest studies of EBUS-TBNA specifically examining the incidence of granulomatous inflammation in the setting of known malignancy or suspected recurrence,4,5,7 the presence of these 2 diagnoses remains mutually exclusive.

We present a case report of a patient undergoing EBUS-TBNA for intrathoracic lymphadenopathy, in which the coexistence of both granulomatous inflammation and metastatic disease was discovered within the same lymph node stations.

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CASE REPORT

A 69-year-old woman was noted to have a breast mass on physical examination. She had previously undergone a mastectomy, followed by adjuvant chemotherapy and radiation therapy for invasive ductal breast carcinoma on the contralateral side approximately 10 years earlier. She underwent computed tomography of the chest revealing mediastinal lymphadenopathy (Fig. 1). She was referred for and underwent EBUS-TBNA before planned surgical resection of her breast mass. During the procedure, stations 4R and 7 were sampled using a 21-G EBUS Needle (Olympus Inc., Center Valley, PA). Specimens were processed within liquid Cytolyt medium and 10% neutral-buffered formalin as rinses without the use of onsite cytologic analysis. Final analysis from both lymph node stations revealed metastatic adenocarcinoma consistent with breast origin (Fig. 2A). These same samples also revealed collections of epithelioid histiocytes forming sarcoidal-type granulomas. Asteroid bodies, which are typical of but not specific for sarcoidosis, were also present (Fig. 2B).

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

She subsequently initiated treatment for her metastatic breast carcinoma and remains alive 22 months after her diagnosis. She has no clinical manifestations of, nor has she yet to receive treatment for her granulomatous inflammation.

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DISCUSSION

Current EBUS-TBNA data suggests that malignancy and granulomatous inflammation occur in exclusivity within lymph nodes,4,7 with authors in 1 study noting, “…a finding of non-necrotizing granulomas on EBUS-TBNA…should serve to indicate the absence of lymph node metastases.”7 After the publication of this manuscript, Trisolini et al8 presented a case report of a single patient with stage IIIA non–small cell lung cancer in which they identified both granuloma and metastatic lung cancer within a station 7 lymph node. Tomimaru et al3 has also previously reported on the coexistence of carcinoma and granulomatous inflammation in pathologic samples of 4 patients (4/1733 patients, 0.2%) undergoing lymphadenectomy during surgical resection of lung cancer. Herein, we present an additional case confirming this phenomenon in EBUS-TBNA, further adding to the literature base.

Granulomatous inflammation (sarcoid-like reactions) in patients with solid tumors has been well described previously. Brincker9 reports an incidence of up to 20% in his review of granulomatous reaction and metastatic tumor, however, it remains difficult to critically review because of publication dates (1957 to 1975) and lack of publication within the English language. The sampling process for these lymph nodes was not consistently described (eg, lymphadenectomy, needle aspiration, etc.), nor was the true incidence of intranodal coexistent granulomatous inflammation and metastatic disease versus the coexistence of granulomatous inflammation and malignancy within overall lymph node sampling well described.1

Although the clinical implications of the coexistence of granulomatous inflammation and carcinoma remain unclear, the implications during diagnostic testing are clear. The presence of granulomatous inflammation within a needle aspiration sample cannot guarantee the absence of coexisting malignancy. While the incidence of this phenomenon appears rather rare, it remains currently difficult to truly define its incidence. Further study of this phenomenon remains important, especially with the expanding use of EBUS-TBNA as a diagnostic modality for intrathoracic lymphadenopathy. Previous data have demonstrated the occurrence (<1%) of both granulomatous inflammation and malignancy in certain carcinomas, most notably lymphoma,9 however, this coexistence has not been well described in solid tumors. In breast cancer, numerous reports have identified granulomatous-like reactions associated with the primary tumor, however, this coexistence does not appear to occur within lymph node pathology.10 Of note, within our sampling, station 4R demonstrated abundant metastatic tumor and few granulomas, whereas station 7 node yielded abundant granulomas, but rare tumor cells.

The biggest single concern of a bronchoscopist performing endobronchial staging procedures remains the ability to accurately stage the mediastinum in an attempt to offer appropriate treatment. Although this coexistence phenomenon is likely quite rare, its presence is concerning. One potentially dangerous situation could occur in the setting of a rapid onsite cytology diagnosis of granulomatous inflammation with the cessation of further lymph node sampling based on this information. Certain authors have suggested the need to remain “vigilant” during EBUS-TBNA,5 noting that the identification of granulomatous inflammation in the setting of known or suspected malignancy should not lead to premature termination of the procedure. However, they describe a multinodal station sampling in which some lymph nodes were involved with granuloma and others involved with malignancy. Although this argument points out the flaw in assuming that all disease within the thorax is related to the same disease (all lymphadenopathy is granuloma or all disease is malignancy), it unfortunately does not directly address the potential for intranodal variability of disease. The authors are unaware of any current reports or data identifying patients receiving inappropriate care resulting from this particular phenomenon and admit that the true incidence is likely rare. However, the potential for misdiagnosis is not without consequence (ie, unnecessary thoracotomy).

In conclusion, we present a case identifying the presence of coexisting granulomatous inflammation and malignancy within the same lymph node station in a patient with metastatic breast cancer. Bronchoscopists performing TBNA procedures need to be aware of this rare, but possible occurrence. Further research is warranted attempting to identify the true incidence of this phenomenon, its implications during intraprocedural testing, as well as its impact on patient outcomes.

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REFERENCES

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Keywords:

EBUS-TBNA; granuloma; intrathoracic lymphadenopathy; metastatic breast cancer

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