Легкомерный амилоидоз диагностируется Branbronchial Lung Biopsy: Three-Case Series with Divide Radiodial Provisions.

Introduction

Pulmonary amyloidosis is a rare disorder characterized by extracellular deposition of insoluble amyloid fibrils within the lung. It is broadly classified into localized and systemic forms, the latter including immunoglobulin light‐chain (AL) amyloidosis, AA amyloidosis associated with chronic inflammatory diseases, and hereditary amyloidosis. Pulmonary involvement may occur as part of systemic disease or as localized amyloid deposition [ 1 , 2 , 3 , 4 ].

Pulmonary amyloidosis presents with a wide spectrum of radiological manifestations, including nodular lesions, diffuse interstitial abnormalities, and tracheobronchial involvement, often mimicking malignant tumours or other diffuse lung diseases. Histopathological confirmation is required, and conventional forceps transbronchial lung biopsy (TBLB) may provide a less invasive diagnostic alternative in selected patients [ 2 , 3 , 4 ].

Herein, we report three cases of pulmonary amyloidosis with diverse radiological manifestations diagnosed by TBLB and discuss the distinct clinical roles of conventional forceps TBLB according to radiological and systemic disease presentation.

Case Series

Case 1

A 73‐year‐old man with a history of smoking (45 pack‐years) and occupational welding exposure was referred to our hospital after multiple pulmonary nodules were incidentally detected on chest computed tomography (CT) performed for exertional dyspnea. Chest CT revealed a calcified mass in the right upper lobe, consolidation in the right middle lobe, and multiple nodules in the right lower lobe (Figure 1 ).

Laboratory investigations demonstrated a normal serum free light chain ratio and negative serum and urine immunofixation electrophoresis, with no evidence of monoclonal gammopathy (Table 1 ). Bronchoscopy revealed no endobronchial abnormalities, and six TBLB specimens were obtained from the right B2b without complications. Histopathological examination demonstrated eosinophilic amorphous deposits with mild lymphocytic infiltration. Direct Fast Scarlet (DFS) staining was positive with apple‐green birefringence under polarized light. The deposits were resistant to potassium permanganate treatment, consistent with non‐AA amyloidosis. Additional amyloid typing identified AL λ amyloidosis (Figure 4A,B ).

Systemic evaluation, including gastrointestinal biopsies, transthoracic echocardiography, technetium‐99 m pyrophosphate scintigraphy, and bone marrow examination, showed no extrapulmonary amyloid deposition, cardiac amyloidosis, or plasma cell neoplasia. The patient was diagnosed with localized nodular pulmonary AL amyloidosis and remained clinically and radiologically stable without specific treatment for 61 months.

Case 2

A 79‐year‐old man with a history of smoking (43 pack‐years) and occupational welding exposure was referred to our hospital after multiple pulmonary nodules were detected on chest CT performed for cough and sputum production. CT revealed multiple nodules and mass‐like lesions, accompanied by right pleural thickening. PET‐CT demonstrated FDG uptake in both the pulmonary nodules and thickened pleura (Figure 2 ).

Laboratory investigations demonstrated a normal serum free light chain ratio and negative serum and urine immunofixation electrophoresis, with no evidence of monoclonal gammopathy (Table 1 ). Bronchoscopy revealed no endobronchial abnormalities, and 20 TBLB specimens were obtained from the right B9a without complications. Histopathological examination demonstrated eosinophilic amorphous deposits predominantly around small vessels and within the bronchial and alveolar interstitium. DFS staining was positive with apple‐green birefringence under polarized light, and the deposits were resistant to potassium permanganate treatment, consistent with non‐AA amyloidosis (Figure 4C,D ).

Systemic evaluation, including gastrointestinal and skin biopsies and bone marrow examination, showed no extrapulmonary amyloid deposition or plasma cell neoplasia. The patient was diagnosed with localized nodular pulmonary non‐AA amyloidosis and remained clinically and radiologically stable without specific treatment for 12 months.

Case 3

A 75‐year‐old woman developed anorexia in approximately April 2022 and was evaluated at another hospital in August 2022. Upper and lower gastrointestinal endoscopy revealed no evidence of malignancy. Chest computed tomography (CT) demonstrated interlobular septal thickening, and the serum Krebs von den Lungen‐6 (KL‐6) level was markedly elevated at approximately 2200 U/mL. She was referred to our hospital on October 26, 2022, for further evaluation. During the preceding 6 months, her body weight had progressively decreased from 50 to 43 kg. The elevated KL‐6 level was confirmed on repeat testing at our hospital. She also presented with exertional dyspnea and bilateral lower extremity edema.

At our hospital, the serum brain natriuretic peptide level was 122.5 pg/mL, and transthoracic echocardiography demonstrated a left ventricular ejection fraction of 46% with diffuse left ventricular hypokinesis. Although concomitant heart failure was considered after consultation with a cardiologist, we considered that heart failure alone could not adequately explain the overall clinical presentation, particularly the persistently elevated KL‐6 level and progressive weight loss. Contrast‐enhanced chest CT demonstrated bilateral peripheral interlobular septal thickening without pulmonary nodules or masses, and no other findings provided a clear explanation for her systemic manifestations (Figure 3 ).

Because the aetiology of the pulmonary abnormalities and progressive systemic symptoms remained unclear, bronchoscopy was performed to obtain a diagnostic clue. No endobronchial abnormalities were observed, and six transbronchial lung biopsy (TBLB) specimens were obtained from the right B1, B5, and B6 without complications. Histopathological examination unexpectedly demonstrated eosinophilic amorphous deposits within the alveolar interstitium and around small vessels, accompanied by scattered plasma cells. Direct Fast Scarlet staining was positive, and the deposits were resistant to potassium permanganate treatment, consistent with non‐AA amyloidosis. Immunohistochemical analysis demonstrated κ‐positive and λ‐negative amyloid deposits, whereas no infiltration of CD138‐positive plasma cells was identified in the lung tissue (Figure 4E,F ).

The unexpected detection of pulmonary amyloid deposition by TBLB prompted further systemic evaluation for amyloidosis. Random biopsies of the gastrointestinal tract, kidney, and skin all demonstrated amyloid deposition, confirming systemic involvement. Subsequent haematological evaluation revealed marked monoclonal gammopathy, with serum free κ and λ light‐chain levels of 8660 mg/L and 14.8 mg/L, respectively (κ/λ ratio, 585.24), together with serum M protein and urinary Bence Jones protein κ (Table 1 ). Bone marrow examination demonstrated 35% clonal plasma cells expressing CD138 with marked κ light‐chain predominance, consistent with multiple myeloma, although no amyloid deposition was identified in the bone marrow.

Based on these findings, the patient was diagnosed with systemic AL (κ‐type) amyloidosis associated with multiple myeloma, with diffuse alveolar‐septal pulmonary involvement. Treatment with daratumumab, lenalidomide, and dexamethasone (DLd) was initiated on November 14, 2022. However, despite treatment, the underlying disease progressed and the patient died on February 19, 2023.

Discussion

Pulmonary amyloidosis is an uncommon manifestation of amyloid deposition and may occur as localized or systemic disease. Localized pulmonary amyloidosis generally follows an indolent course, whereas systemic AL amyloidosis with pulmonary involvement is frequently associated with plasma cell dyscrasia and poorer outcomes [ 1 , 2 , 3 , 4 , 5 , 6 ]. Radiological manifestations include tracheobronchial, nodular parenchymal, and diffuse alveolar‐septal patterns [ 5 , 6 , 7 ]. Nodular pulmonary amyloidosis may mimic malignancy, including FDG‐avid lesions, whereas diffuse alveolar‐septal amyloidosis typically manifests as reticular opacities, interlobular septal thickening, or diffuse interstitial abnormalities [ 2 , 3 , 5 , 6 , 8 ]. In our series, Cases 1 and 2 presented with nodular disease without systemic involvement, whereas Case 3 showed subtle interlobular septal thickening associated with systemic AL amyloidosis and multiple myeloma.

Histopathological confirmation remains essential [ 1 , 2 , 3 , 4 , 5 , 6 , 9 ]. Conventional forceps TBLB has been used for several decades. Kline et al. reported three patients with pulmonary parenchymal amyloidosis diagnosed by transbronchial biopsy [ 10 ], and Govender et al. reported 25 patients with amyloid lung disease diagnosed by transbronchial biopsy, including focal and diffuse interstitial patterns, without procedure‐related complications [ 11 ]. Thus, the feasibility of conventional forceps TBLB is established, but its clinical role may differ according to disease presentation. In Cases 1 and 2, TBLB established the diagnosis of nodular lesions mimicking malignancy; subsequent systemic evaluation supported localized pulmonary amyloidosis and observation. In contrast, diffuse alveolar‐septal amyloidosis is frequently associated with systemic disease. Yamada et al. reported that three of five patients with diffuse alveolar‐septal amyloidosis were diagnosed by TBLB [ 12 ]. In Case 3, pulmonary amyloid was unexpectedly identified by TBLB before monoclonal gammopathy or extrathoracic amyloid deposition was recognized, prompting systemic and haematological evaluation that revealed systemic AL amyloidosis associated with multiple myeloma.

Transbronchial lung cryobiopsy (TBLC) should be distinguished from conventional forceps TBLB. Fujimoto et al. reported two cases of pulmonary amyloidosis diagnosed by TBLC, which can provide larger specimens than conventional forceps biopsy [ 13 ]. However, evidence regarding TBLC in pulmonary amyloidosis remains limited. All three patients in our series were diagnosed using conventional forceps TBLB.

Procedural safety should also be considered because amyloid deposition may involve pulmonary vessels. Although no complications occurred in our three patients or in the 25‐patient series reported by Govender et al. [ 11 ], Strange et al. reported fatal pulmonary haemorrhage followed by massive arterial air embolism after transbronchial biopsy in pulmonary amyloidosis [ 14 ]. The diagnostic benefit of TBLB should therefore be balanced against procedural risk, with careful patient selection and appropriate preparation for bleeding.

This study is limited by its small sample size and retrospective nature and cannot establish the diagnostic yield or safety of conventional forceps TBLB. Nevertheless, these cases illustrate distinct clinical roles of TBLB across different presentations of pulmonary amyloidosis.

In conclusion, pulmonary amyloidosis should be considered in both nodular and diffuse pulmonary abnormalities. Conventional forceps TBLB may provide useful diagnostic tissue in selected patients, although its role differs according to radiological and systemic context, and bleeding risk should be considered. In nodular disease, TBLB may distinguish localized amyloid lesions from malignancy, whereas in diffuse alveolar‐septal disease, pulmonary amyloid identified by TBLB may provide an initial clue prompting evaluation for underlying systemic amyloidosis.

Author Contributions

Masaki Tanaka conceived the study, collected the clinical data, interpreted the findings, and drafted the manuscript. All authors contributed to patient management, revised the manuscript critically for important intellectual content, and approved the final version of the manuscript.

Funding

The authors have nothing to report.

Consent

The authors declare that written informed consent was obtained from all the patients for the publication of this manuscript and accompanying images and attest that the form used to obtain consent from the patients complies with the Journal requirements as outlined in the author guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.

Tanaka M., Ozaki Y., Otsuka T., et al., “Pulmonary Amyloidosis Diagnosed by Transbronchial Lung Biopsy: A Three‐Case Series With Diverse Radiological Manifestations,” Respirology Case Reports 14, no. 9 (2026): e70757, 10.1002/rcr2.70757.

Associate Editor: Tomohiro Handa

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Associated Data

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.