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Pulmonary Nodular Lymphoid Hyperplasia in the Eye of Radial Endobronchial Ultrasound


Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare, benign lymphoproliferative disorder often manifesting as a solitary pulmonary nodule (SPN). Once a malignant cause of SPN is ruled out, it presents a diagnostic dilemma to clinicians due to histopathological overlap with diseases like mucosa-associated lymphoid tissue (MALT) lymphoma and IgG4-related sclerosing disease. We report an adult patient who presented with incidental finding of a SPN, and was subsequently diagnosed with PNLH via a combined technique of radial-endobronchial ultrasound (R-EBUS), virtual bronchoscopic navigation (VBN), and cryobiopsy. We discuss the sonographic appearance and histopathological morphology of PNLH, and the merits of bronchoscopic techniques in averting surgical intervention of SPN. This is the first reported sonographic appearance of PNLH under radial-endobronchial ultrasound (R-EBUS).


Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare, benign lymphoproliferative disorder which can present as a solitary pulmonary nodule (SPN) often in the subpleural or peribronchial region10. The diagnosis of PNLH is challenging due to histopathological overlap with other diseases like extranodal marginal zone lymphoma of MALT and IgG4-related sclerosing disease [1]. Diagnostic surgical resection remains the mainstay of PNLH diagnosis and management [1,2,3], but advanced bronchoscopic tools like virtual navigation, R-EBUS, and cryobiopsy may enable diagnosis while preventing further invasive intervention. We report an adult patient who presented with incidental finding of a SPN, and was subsequently diagnosed with PNLH via a combined technique of radial-endobronchial ultrasound (R-EBUS), virtual bronchoscopic navigation (VBN), and cryobiopsy. We describe the first reported sonographic appearance of PNLH under radial-endobronchial ultrasound (R-EBUS), and its histopathology. The histopathological characteristics of PNLH and its relation to more malignant conditions are also discussed.

Case Report

A 41-year-old male, active smoker, presented with incidental finding of right upper lobe SPN during routine medical check-up. He denied family history of malignancy and systemic examination was unremarkable. Computed tomography of the thorax confirmed a rounded hypodense peribronchial SPN without a leading airway in the posterior segment of the right upper lobe measuring 2.7 × 2.2 cm. No vessels were seen between the airway and SPN (Fig. 1a). 18F-FDG positron emission tomography scan revealed increased metabolism with a maximum standardized uptake value (SUVmax) of 2.7.

Fig. 1

a Computed tomography of the thorax showing right upper lobe solid SPN (axial view) with no leading airway on lung window (coronal view). b Bronchoscopic view shows real-time VBN pathway guiding transbronchial off road puncture of SPN (left image) with corresponding virtual pathway (right image)

Using a real-time virtual pathway created in the Lung Point VBN System (Broncus Technologies Inc., Mountain View, CA, USA), a flexible bronchoscope (BF-P190, Olympus Medical, Tokyo, Japan) was guided into the target bronchial sub-segment (Fig. 1b). At the predetermined target site, a guide sheath with R-EBUS probe (UM-S20-17S, Olympus Medical, Tokyo, Japan) was simultaneously inserted, confirming an adjacently orientated lesion as predicted by the CT scan (Fig. 2a). A bidirectional guiding device (CC-6DR-1, Olympus Medical, Tokyo, Japan) was then used to puncture perpendicularly through the bronchial wall under direct vision. R-EBUS was re-deployed to confirm the position of the guide sheath within the core of the lesion, and biopsy samples were taken using biopsy forceps and a 1.9-mm cryoprobe under fluoroscopic guidance.

Fig. 2

a Pre-off road access fluoroscopic and R-EBUS view shows adjacent lesion. b Post-off road access fluoroscopic and R-EBUS view shows concentric lesion, confirming placement of guide sheath within core of the SPN

R-EBUS demonstrated a concentric, mixed echogenicity lesion with multiple homogeneous nodules within the lesion (Fig. 2b). Histopathological examination revealed dense lymphoplasmacytic cell infiltration with reactive lymphoid follicles exhibiting prominent germinal centers (Fig. 3a) with Russell bodies (Fig. 3b). The lymphoid population was composed of a mixture of mature B and T lymphocytes with no evidence of light chain restriction on Kappa and Lambda immuno-stain. This constellation of findings and clinical progress led to a diagnosis of PNLH after discussion in a multidisciplinary board meeting, with subsequent radiological surveillance demonstrating a stable lesion over 12-month duration.

Fig. 3

a Lymphoid follicles with germinal center and dense lymphoplasmacytic cells infiltration (× 20). b Russell bodies (white arrow) (× 40)

Discussion and Conclusions

The differential diagnoses of PNLH include B cell lymphomas such as marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) and immunoglobulin (Ig) G4-related sclerosing disease (IgG4-RSD) [1]. However, definite diagnosis of PNLH is often difficult due to overlapping histopathological features and paucity of data regarding its clinical course and the utility of FDG PET/CT in confirming PNLH [2]. MALT lymphoma is distinguished histologically by light chain restriction and Dutcher bodies [1], both of which were not seen in our patient’s sample. Meanwhile, IgG4-RSD presents more commonly as multiple lung nodules alongside multiorgan involvement [1], in contrast to the asymptomatic presentation of SPN in our patient. Histologically, IGG4-RSD presents as a lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells with occasional eosinophils and vasculitic features [1]. The absence of eosinophils and vasculitic features in our patient’s sample was consistent with PNLH; hence, IgG4-staining was not carried out.

Most sources advocate diagnostic surgical resection as the gold standard of management for PNLH [1,2,3], but its associated risks may exclude certain patients. This has led to the emergence of bronchoscopic methods as a diagnostic tool. R-EBUS is a bronchoscopic imaging device which enables real-time sonographic imaging of lesions within or adjacent to pulmonary airways. R-EBUS sonographic appearance may differentiate between malignant and benign pulmonary lesions [4]. In a study of in vitro transthoracic sonograms of lymph nodes in non-Hodgkin’s follicular type lymphoma, sonographic pattern of mixed echogenicity with micronodular patterns was consistent with histological morphology of large, round hypertrophied follicles within the lymph node [5]. Similarly, we postulate that the homogenous nodules seen on our patient’s R-EBUS sonography may represent the reactive lymphoid follicles seen on histological examination. To our knowledge, the sonographic appearance of PNLH has yet to be reported and further studies need to be conducted into the correlation of R-EBUS sonogram and histopathology.

Harnessing the combined utilities of R-EBUS, VBN, and cryobiopsy allowed us to obtain a representative sonographic and histological sample in diagnosing PNLH. Some potential challenges in the use of R-EBUS include suboptimal tissue yield, with R-EBUS meta-analysis reporting a yield of around 50% for adjacent orientated lesions [6]. However, the emergence of bronchoscopic-guiding modalities such as virtual bronchoscopic navigation (VBN) has improved navigation through the airways, with reported biopsy success rates ranging 67 to 84% [7]. Cryobiopsy has been reported as a valid surrogate for surgical lung biopsy in patients with lymphoproliferative disease [8]. Single-center studies have demonstrated superior yields and larger tissue sizes in the diagnosis of peripheral lung lesions [9], with one single-center study demonstrating a yield of up to 74.2% [10]. This method could potentially facilitate bronchoscopic therapeutic options to treat peripheral pulmonary lesions in the future for patients deemed not suitable for surgical intervention.

We demonstrated that a combination of a reassuring sonographic appearance of PNLH on R-EBUS and confirmatory histopathological diagnosis via cryobiopsy was sufficient in stratifying the malignant potential of our patient’s SPN and thus avoiding high-risk surgical biopsy. However, regular radiological and clinical follow-up is required. In the absence of larger surgical resection specimens other diagnosis such as lymphocytic granulomatosis, IgG4D-related disease, and lymphoma could not be immediately ruled out.


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Correspondence to Larry Ellee Anak Nyanti.

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Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

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Nyanti, L.E.A., Kho, S.S., Teoh, P.I. et al. Pulmonary Nodular Lymphoid Hyperplasia in the Eye of Radial Endobronchial Ultrasound. SN Compr. Clin. Med. 2, 242–245 (2020).

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  • Radial endobronchial ultrasound
  • Pulmonary nodular lymphoid hyperplasia
  • Solitary pulmonary nodule
  • Virtual bronchoscopic navigation
  • Cryobiopsy