Aspergillus nodules (AN) are an unusual form of chronic pulmonary aspergillosis. On the other hand, pulmonary nodular lymphoid hyperplasia (PNLH) is classified as a reactive pulmonary lymphoproliferative disorder. A 65-year-old male was referred to our hospital due to a nodule in the left upper lobe. Histologically, a mixture of prominent lymphoid follicular formation, and hyaline necrosis were observed. Grocott staining revealed morphological forms of Aspergillus spp. in the necrosis. The final clinical diagnosis was suspected AN histologically consistent with PNLH. This case suggests that there may be PNLH cases in which local infection with Aspergillus contributes to its pathophysiology. J. Med. Invest. 70 : 499-502, August, 2023.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare non-neoplastic disease that presents with mass lesions in the lung. It is radiologically difficult to differentiate it from adenocarcinoma of the lung or pulmonary lymphoma. There has been no consensus regarding the treatment of PNLH; however, in many case series, patients usually undergo surgical resection for diagnostic and therapeutic purposes. Here, we present the case of a 60-year-old Chinese male who presented with cough and hemoptysis. A computed tomography scan of the thorax revealed a mass-like lesion. A biopsy was performed which showed lymphocytic pneumonitis. He was treated with a tapering dose of corticosteroids with good clinical and radiological outcomes. Upon a subsequent review of the case, a diagnosis of PNLH was made. This case report suggests that corticosteroids may be an alternative therapy to surgical resection. They have the advantage of being non-invasive and can be used in patients who are otherwise not surgical candidates due to other comorbidities. However, further research is required before we can recommend corticosteroids as a treatment for PNLH.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a very rare disease, and it is difficult to diagnose PNLH and distinguish it from mucosa-associated lymphoid tissue (MALT) lymphoma. In addition, information on bronchoalveolar lavage fluid (BALF) analyses is lacking. We herein report a 36-year-old Japanese woman diagnosed with PLNH by a surgical biopsy and analysis of BALF. The BALF showed an increase in B-cell marker-positive lymphocytes, normal patterns of B-cell clonality, mucosa-associated lymphoid tissue 1 gene, and immunoglobulin heavy chain at 14q32 translocations. We also reviewed Japanese cases of PNLH described in Japanese or English to explore the characteristics of such cases.

BACKGROUND: Pulmonary nodular lymphoid hyperplasia (PNLH) is a rare benign illness. Due to atypical clinical and radiographic presentations, diagnosis largely depends on postoperative pathological examination. Thus, preoperative misdiagnosis is often occurred.
METHODS: We present a case of asymptomatic PNLH that was seen as ground-glass opacity (GGO) on computed tomography (CT). After 3-year observation, the diagnosis tends to adenocarcinoma owing to increasing density of the node and vessel convergence sign, which were signs of malignancy. Video-assisted segmentectomy (S10) was carried out. Histopathologic examination of postoperative specimen showed follicular lymphoid hyperplasia with interfollicular lymphoplasmacytosis, consistent with PNLH. The follow-up chest CT images showed no recurrence or metastasis.
CONCLUSIONS: Although it is a benign disease, PNLH can exhibit malignant signs in the imaging examinations, which could lead to misdiagnosis. This reminds us of the uncertainty between imaging findings and diagnosis. The diagnosis depends on postoperative pathological examination. Volume doubling time is a potential parameter to differentiate PNLH from lung cancer.

Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells.