Pulmonary Light Chain Deposition Disease Research Articles

Phenotypes and outcome of diffuse pulmonary non-amyloid light chain deposition disease.

Light chain deposition disease (LCDD) is a very rare entity. Clinical manifestations of LCDD vary according to the organs involved. Data on pulmonary LCDD are scarce and limited to small series or case reports. This study aimed to describe the characteristics and outcome of diffuse pulmonary non-amyloid LCDD localized to the lungs. A multicenter retrospective cohort study was conducted. Clinical characteristics were collected, and chest CTs were centrally reviewed. The diagnosis of pulmonary non-amyloid LCDD was confirmed by immunohistochemistry. Thirty-one cases were identified (68% female), with a median age at diagnosis of 50 years (IQR 20). Baseline FEV1/FVC was < 0.70 in 45% of patients. Mean (± SD) FEV1 and DLCO were 86% ± 26.2 and 52% ± 23.9, respectively. CT revealed peculiar patterns of thin-walled cysts (58%) and thin-walled cystic bronchiectases (27%). Increased serum kappa light chain was found in 87% of patients. Histological analysis showed kappa light chain deposits in all patients, except one with lambda chain deposits. Median annual FEV1 decline was 127 ml (IQR 178) and median DLCO decline was 4.3% (IQR 4.3). Sixteen patients received immunomodulatory treatment or chemotherapy; serum light chain levels decreased in 9 cases (75%), without significant improvement in FEV1 (p = 0.173). Overall, 48% of patients underwent bilateral lung transplantation. Transplant-free survival at 5 and 10 years were 70% and 30%, respectively. An annual FEV1 decline greater than 127 ml/year was associated with increased risk of death or transplantation (p = 0.005). Diffuse pulmonary LCDD is characterised by female predominance, a peculiar imaging pattern with bronchiectasis and/or cysts, progressive airway obstruction and severe DLCO impairment, and poor outcome. Lung transplantation is a treatment of choice.

A NOVEL CASE OF LYMPHANGIOLEIOMYOMATOSIS AND PULMONARY LIGHT CHAIN DEPOSITION DISEASE

A NOVEL CASE OF LYMPHANGIOLEIOMYOMATOSIS AND PULMONARY LIGHT CHAIN DEPOSITION DISEASE

LIGHT CHAIN DEPOSITION DISEASE: WHAT?

TOPIC: Diffuse Lung Disease TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary light chain deposition disease (PLDD) is an exceptionally rare diagnosis characterized by the deposition of nonamyloid light chains leading to progressive dyspnea and airflow obstruction. Cystic PLDD demonstrates extensive, bilateral thin-walled cysts. Pathologically, deposition of amorphous eosinophilic material surrounded by giant cell reaction that does not react Congo-Red staining is noted. Lung transplantation can be curative. CASE PRESENTATION: A 38-year-old female with past medical history of mixed connective tissue disease with lupus-like features, and long-term tobacco use was seen in the pulmonology office for worsening dyspnea on exertion and dry cough. CT-Chest showed bilateral and multiple thin-walled cysts. Pulmonary function tests were unremarkable. VEGF-D, Alpha-1-antitrypsin genotype, and HIV were unremarkable. A left upper lobe video assisted thorascopic lung biopsy was performed. Pathology was consistent with pulmonary light chain deposition disease associated with giant cell reaction and patchy lymphocytic infiltrates, without evidence of lymphoproliferative disease. There were amyloid-like nodules that did not react with Congo-Red, and staining for Pulmonary Langerhans Histiocytosis was negative.Further work-up revealed normal cell counts, kidney function, and a normal SPEP and UPEP. Free light chains and Kappa/Lambda ratio were slightly elevated. Bone marrow biopsy, FISH analysis, and karyotype were performed to rule-out a clonal process. These studies were unremarkable. She was referred to a transplant center. DISCUSSION: Light chain deposition disease is a result of monoclonal immunoglobulin deposits, and typically involves the renal, hepatic, and cardiac systems. Isolated pulmonary involvement (PLDD) is exceptionally rare, and is only a recently noted phenomenon. Cystic-predominant PLDD is characterized by extensive, bilaterally thin-walled and progressively expanding cysts that are similar in appearance to lymphangioleiomyomatosis (LAM). Clinically, PLDD is characterized by progressive dyspnea that correlates with worsening obstructive disease on PFT's. Free light chains and the Kappa/Lambda ratio are often elevated without other lab abnormalities. Surgical biopsy should be obtained, particularly if the patient has a tobacco history, as differentiating PLDD from Pulmonary Langerhans is crucial. Pathologically, PLDD is similar to amyloidosis, with amorphous eosinophilic material in cystic walls that stains positive on hematoxylin and eosin. The amorphous material is usually surrounded by giant cell reactions, and material can also be noted in airways and blood vessels. However, there is no reaction in Conge-Red staining. Treatment for PLDD is limited to lung transplantation. CONCLUSIONS: Cystic lung disease often requires surgical biopsy, particularly if rheumatologic or hematologic comorbidities are present. REFERENCE #1: Colombat M, Caudroy S, Lagonotte E, et al. Pathomechanisms of cyst formation in pulmonary light chain deposition disease. Eur Respir J 2008;32:1399-403. 10.1183/09031936.00132007 REFERENCE #2: Khawaja et al. Shedding Light on Cystic Lung Disease. The Expert Clinician. 2019. DISCLOSURES: No relevant relationships by Kaitlyn Musco, source=Web Response No relevant relationships by Dylan Soller, source=Web Response No relevant relationships by Richard Strobel, source=Web Response

EXTENSIVE CYSTIC LUNG DISEASE IN EXTRANODAL MARGINAL ZONE B CELL LYMPHOMA (MALT LYMPHOMA) OF THE LUNG WITH LIGHT CHAIN DEPOSITION DISEASE

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT Lymphoma) is a rare disorder, but is the most common cause of primary pulmonary lymphoma involvement. Cystic changes along with nodularity has been previously reported in MALT lymphomas along with light chain deposition disease (LCDD). CASE PRESENTATION: A 44 y/o previously smoking female patient presented with a 3-year history of progressive dyspnea in the setting of extensive cystic lung disease. Her extensive lung cysts had previously raised concern for lymphangioleiomyomatosis (LAM) and she had undergone an open lung biopsy (OLB) about 2 years prior. She also had a 10-year history of Rheumatoid Arthritis (RA) for which she had previously received methotrexate, adalimumab and leflunomide. The OLB was negative for LAM, but no alternative diagnosis was made based on the biopsy results. Due to progressive dyspnea, she presented to our facility where a fresh evaluation of her case was undertaken. A repeat CT Chest again confirmed extensive cystic lung changes that were not present 12 years ago and had minimally progressed from the time of OLB two years ago (figure 1). Pulmonary function testing (PFTs) showed a severe obstructive pattern with a positive bronchodilator response. Laboratory testing confirmed positive results for rheumatoid factor, CCP, ANA as well as SSA & SSB antibodies. A review of the OLB confirmed the presence of an atypical lymphoplasmacytic infiltrate associated with nodular kappa light chain deposition disease (LCDD). The overall pattern was consistent with extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). The biopsy confirmed the presence of cystic changes within the nodular light chain deposits. PET scan was negative for extrathoracic lymphoma and the patient was started on Rituximab. DISCUSSION: We present a case of pulmonary MALT Lymphoma with LCDD presenting with extensive cystic lung disease and severe airflow obstruction. The case was initially mistaken for LAM and appropriate therapy was delayed for 2 years. MALT lymphomas with LCDD are rare causes of pulmonary cystic disease and generally have a good prognosis with an overall 5-year survival rate exceeding 80% and a median survival over 10 years. Given the positive Sjogren's antibodies and the presence of lung cysts; lymphocytic interstitial pneumonia (LIP) was also considered in the differential diagnosis. The presence of severe airflow obstruction on lung function was somewhat atypical in this case and a component of bronchiolitis obliterans from RA could not be entirely excluded. CONCLUSIONS: Extranodal marginal zone B cell lymphoma of the lung can present with extensive cystic lung disease that can mimic other common causes of cystic lung disease such as LAM, LIP and Birt Hogg Dube disease and PLCH. Prognosis is generally good and Rituximab is the most commonly used initial treatment approach. REFERENCE #1: pulmonary and nodular cystic light chain deposition disease: a retrospective review of 10 cases. Baqir M et al. Respir Med. 2020 Apr; 164:105896. REFERENCE #2: Nodular pulmonary light chain deposition disease: an entity associated with Sjögren syndrome or marginal zone lymphoma. Arrossi AV et al. J Clin Pathol. 2016 Jun; 69(6): 490-6. REFERENCE #3: Pulmonary mucosa-associated lymphoidtissue lymphoma revisited. Borie R et al. Eur Respir J 2016; 47: 1244-1260. DISCLOSURES: No relevant relationships by Vaibhav Ahluwalia, source=Web Response No relevant relationships by Hasan Ahmad Hasan Albitar, source=Web Response No relevant relationships by Vivek Iyer, source=Web Response

WHEN LIGHTNING STRIKES TWICE: A CROSSOVER SYNDROME WITH LIGHT CHAIN DEPOSITION AND LYMPHOID INTERSTITIAL PNEUMONIA

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Light chain deposition disease (LCDD) is a rare cystic lung disease, involving monoclonal proliferation and deposition of light chains. Lymphoid Interstitial Pneumonia (LIP) is an uncommon interstitial lung disease (ILD) usually seen with connective tissue disorders (CTD). We present a challenging case involving the co-existence of LCDD and LIP. CASE PRESENTATION: We present the 25-year long clinical course of a 47-year-old male who was initially diagnosed with a mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland, treated with excision. Over the subsequent 5-10 years, he was diagnosed with rheumatoid arthritis and Sjogren’s syndrome. Treatment with methotrexate was complicated by the development of human anti-murine antibodies. He also developed progressive cough and dyspnea. Computed Tomography (CT) imaging of the chest revealed bilateral nodules and interstitial infiltrate, suggestive of LIP. Right lower lobe wedge resection was performed; histopathology demonstrated lymphoplasmacytic infiltrate and eosinophilic proteinaceous deposits which were negative on Congo red staining. Immunohistochemistry revealed predominantly kappa light chains within the eosinophilic material. Serial follow-up imaging was notable for the development of diffuse cystic lung disease. He was diagnosed with LCDD and was treated with bortezomib, but developed Steven-Johnson syndrome. This was followed by treatment with lenalidomide and then cyclophosphamide. A follow up positron emission tomography (PET) CT scan showed no change in the size of pulmonary nodules. The patient was also trialed on bendamustine and ofatumumab, an anti-CD20 monoclonal antibody, with no significant improvement. A recent chest CT, obtained 15 years following the onset of lung disease, demonstrated wide-spread thin walled cysts and nodular disease (Fig 1,2). His symptoms have stabilized with oxygen supplementation and treatment of exacerbations with steroids and antibiotics, and he is currently on surveillance. DISCUSSION: LCDD, an entity caused by plasma cell proliferation and monoclonal light chain deposits in various organs often found in association with lymphoproliferative conditions, can manifest as diffuse cystic lung disease. (1) It has a poor prognosis. Treatment options include immunomodulators and chemotherapeutic agents, including bortezomib, daratumumab, and bendamustine. LIP, an ILD, is usually seen in patients with CTD and HIV. (2) Therapeutic options include immunosuppressants such as rituximab and cyclophosphamide. Our case was challenging, given the confluence of two syndromes- LIP with underlying rheumatic conditions, and LCDD due to a lymphoproliferative disorder. Multiple avenues of treatment were attempted but failed to produce an objective improvement in disease course. CONCLUSIONS: LIP and LCDD can occur in tandem; enrollment in study trials should be considered for these patients given poor prognosis. Reference #1: Arrossi AV, Merzianu M, Farver C, et al. Nodular pulmonary light chain deposition disease: an entity associated with Sjögren syndrome or marginal zone lymphoma. J Clin Pathol. 2016 Jun;69(6):490-6. Reference #2: Swigris JJ, Berry GJ, Raffin TA, et al. Lymphoid interstitial pneumonia: a narrative review. Chest. 2002 Dec;122(6):2150-64. DISCLOSURES: No relevant relationships by Pius Ochieng, source=Web Response No relevant relationships by NISHANT SHARMA, source=Web Response No relevant relationships by Pandi Todhe, source=Web Response

Nodular pulmonary deposition disease in a patient with the acquired immunodeficiency syndrome: a\xa0case report

BackgroundPulmonary nodules are a common cause for concern in patients with human immunodeficiency virus and acquired immunodeficiency syndrome. Most commonly, they are the result of an infection, given the patients’ immunocompromised state; however, in some cases, pulmonary nodules in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome can result from cellular or protein deposits. We report a rare case of nodular pulmonary light chain deposition disease in a patient with acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance.Case presentationA 53-year-old African American woman with acquired immunodeficiency syndrome had pulmonary nodules detected incidentally by imaging of her lungs. Pulmonary tuberculosis was high on the differential diagnosis, but she had a negative test result for pulmonary tuberculosis. Imaging also revealed multiple lucent bone lesions, and earlier in the year, serum protein electrophoresis had shown an immunoglobulin G-kappa monoclonal protein (M spike). She was mildly anemic, so there was concern for progression to myeloma; however, the result of her bone marrow biopsy was unremarkable. Lung biopsy revealed finely granular eosinophilic material with negative Congo red staining, consistent with light chain deposition disease.ConclusionsThe extent of this patient’s light chain deposition disease was thought to be caused by a combination of acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance, and the interval decrease in lung nodule size after restarting antiretroviral therapy confirms this hypothesis and also highlights a potentially unique contribution of the hypergammaglobulinemia to this disease process in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome .

Pulmonary light chain deposition disease: a case series and literature review.

BackgroundLight chain deposition disease (LCDD) is a systemic disorder typically characterized by non-amyloid monoclonal immunoglobulin light chain deposition in tissues. LCDD is recognized as a multisystem disease, in which the kidneys and liver are often affected. However, it is rarely encountered as a localized pulmonary disease. This study set out to characterize the clinical manifestations and features of pulmonary light-chain deposition disease (PLCDD) by conducting a retrospective analysis of clinical data obtained from patients, with the aim of improving clinical understanding of PLCDD.MethodsData from inpatients diagnosed with PLCDD at Shanghai Pulmonary Hospital (Shanghai, China) between January 2010 and December 2018 were retrospectively collected and analyzed.ResultsA total of 4 PLCDD patients confirmed with PLCDD by pulmonary tissue biopsy were analyzed. All of the patients were female and were found by physical examination. Chest images of each patient’s lungs showed multiple cystic cavities with nodules. A history of Sjogren’s syndrome was present with 1 patient, 2 patients were diagnosed with Sjogren’s syndrome after surgery (including 1 diagnosed with Sjogren’s syndrome in the 8th year of follow up), and 3 patients had leukopenia. The longest follow-up period was 8 years. During the follow-up period, 2 patients developed pulmonary lesions (1 patient had an enlarged original cystic lesion in basal segment of right lower lobe 2 years after surgery, while the other developed new nodules 7 years after surgery).ConclusionsPLCDD is characterized by multiple cystic changes with nodules in both lungs and can be easily complicated by lymphoid diseases such as Sjogren’s syndrome. The clinical symptoms cannot be characterized, and the diagnosis depends on lung biopsy.

Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease

AbstractWe previously reported a new form of light chain deposition disease (LCDD) presenting as diffuse cystic lung disorder that differs from the usual systemic form with respect to patient age, the male/female ratio, the involved organs, and the hematologic characteristics. We also demonstrated that the light chains were produced by an intrapulmonary B-cell clone and that this clone shared a stereotyped antigen receptor IGHV4-34/IGKV1. However, we only analyzed 3 patients. We conducted a retrospective study including lung tissue samples from 24 patients with pulmonary LCDD (pLCDD) matched with samples from 13 patients with pulmonary κ light chain amyloidosis (pAL amyloidosis) used as controls. Mass spectrometry–based proteomics identified immunoglobulin κ peptides as the main protein component of the tissue deposits in all patients. Interestingly, in pLCDD, IGKV1 was the most common κ family detected (86.4%), and IGKV1-8 was overrepresented compared with pAL amyloidosis (75% vs 11.1%, P = .0033). Furthermore, IGKV1-8 was predominantly associated with a diffuse cystic pattern (94%) in pLCDD. In conclusion, the high frequency of IGKV1-8 usage in cystic pLCDD constitutes an additional feature arguing for a specific entity distinct from the systemic form that preferentially uses IGKV4-1.

Histoire naturelle d’une forme bronchectasiante de la maladie à dépôts de chaînes légères

The natural history of orphan lung diseases is often unclear. We report the long-term follow-up of a case of bronchiectasis due to pulmonary non amyloid light chain deposition disease (LCDD). A 50-year-old woman who was a smoker, was diagnosed with diffuse thin walled bronchiectasis of uncertain origin after presenting with a respiratory tract infection. Ten years later, the combination of bronchiectasis, the appearance of pulmonary cysts and the identification of increased kappa free light chains evoked the diagnosis of pulmonary LCDD. The diagnosis was confirmed by lung biopsy. No immunoproliferative disorder was identified. During the 12 years follow-up, dyspnea worsened progressively and bronchiectasis and lung cysts extended leading to multicystic lung disease. Pulmonary function tests did not show any ventilatory defect but a small decrease in carbon monoxide transfer factor occurred. We describe the evolution of a rare presentation of isolated pulmonary LCDD, characterized by cystic diffuse atypical bronchiectasis with thin walls, associated with progressive cystic destruction of the lung parenchyma. The possibility of pulmonary LCDD should be considered in cases of atypical bronchiectasis of unknown etiology.

These Aren't the Paraproteins You Have Been Looking for: A Case of Light Chain Deposition Disease

SESSION TITLE: Pulmonary Manifestations of Systemic Disease SESSION TYPE: Affiliate Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 08:45 AM - 10:00 AM INTRODUCTION: Light chain deposition disease (LCDD) is a rare paraproteinemia with primarily renal involvement characterized most commonly by kappa light chain deposits in the kidney. While case reports exist, lung involvement continues to be a rare finding. CASE PRESENTATION: 73 year old male with a past medical history of osteoporosis presented with a two month history of back pain and generalized weakness. Initial presentation was notable for pancytopenia as well as acute kidney injury. Serum protein electrophoresis showed an M-spike in the beta region as well as elevated IgA monoclonal protein with light chain specificity. A bone marrow biopsy was performed and showed extensive serous atrophy and markedly hypocellular marrow. Extensive work-up for multiple myeloma remained non-diagnostic. The patient developed respiratory failure requiring intubation. CTA of chest demonstrated diffuse ground glass opacification throughout all lung fields. There was concern for infection, but all cultures including bronchoalveolar lavage were negative. The patient had worsening respiratory and renal function despite aggressive care. Ultimately, family decided to pursue comfort directed care in accordance with patient’s previously stated wishes regarding prolonged mechanical ventilation and dialysis. Renal specimens obtained at autopsy revealed congo red negative fractured intratubular eosinophilic casts with kappa staining on immunofluorescence consistent with light chain deposition disease. Lung pathology revealed diffuse bronchiolitis obliterans with organizing pneumonia as well as congo red negative amorphous eosinophilic material within alveoli consistent with LCDD. DISCUSSION: Light chain deposition disease remains an important differential in plasma cell dyscrasias, particularly AL amyloidosis. Lung involvement of LCDD is an especially rare finding of an already rare disease. While organizing pneumonia is described with hematologic malignancy, it has not been described with LCDD which typically is characterized by nodules and/or cysts. CONCLUSIONS: This case demonstrates an unusual presentation of a rare manifestation of light chain deposition disease. Recognition of secondary bronchiolitis obliterans as a potential manifestation may help avoid critical delays in treatment. Reference #1: Sayed, RH, et al. “Natural history and outcome of light chain deposition disease.” Blood (2015);126:2805-2810 Reference #2: Sheard, S, et al. “Pulmonary light-chain deposition disease: CT and pathology findings in nine patients.” Clinical Radiology (2015); 70;515-522 DISCLOSURE: The following authors have nothing to disclose: Aaron Lampkin, Peter Miller, Tim Gallagher No Product/Research Disclosure Information

Nodular and Diffuse Pulmonary Light-Chain Deposition Disease—Report of 2 Cases of a Rare and Distinct Entity

Light-chain deposition disease (LCDD) is an unusual multisystem disorder, rarely involving the lung. Pulmonary LCDD can manifest in nodular and cystic forms. While the nodular form may be asymptomatic, the cystic variety usually leads to severe respiratory failure necessitating lung transplantation. Our report consists of 2 cases—one of each type of pulmonary LCDD. We present their clinical/radiological, histological, and ultrastructural features, review the literature, and emphasize the relationship and differentiation of LCDD from immunoglobulin light-chain amyloidosis.

Nodular pulmonary light chain deposition disease: an entity associated with Sjögren syndrome or marginal zone lymphoma

BackgroundLight chain deposition disease (LCDD) is usually a systemic disorder characterised by non-amyloid monoclonal immunoglobulin light chain deposition in tissues. Localised nodular pulmonary (NP) LCDD is a rare and poorly...

Pulmonary light-chain deposition disease: CT and pathology findings in nine patients

To review the clinical features of nine patients with pulmonary light-chain deposition disease (LCDD) and record their high-resolution CT (HRCT) and histopathological findings. Patients with a diagnosis of LCDD on lung biopsy specimen were retrospectively identified. The HRCT characteristics of nodules, cysts, and ancillary findings; change at follow-up; and histopathological findings were documented. Features common to all nine cases were thin-walled cysts. In seven cases, vessels traversing the cysts were identified. The majority of patients (8/9) had at least one pulmonary nodule. There was no zonal predominance of either cysts or nodules. The disease appeared stable in the majority of cases with no serial change in HRCT appearances (5/6 cases with follow-up data, mean duration 29 months). To the authors' knowledge, this is the largest series of pulmonary LCDD patients in the literature, and the first systematic assessment of HRCT findings. Pulmonary cysts are a unifying feature, usually with pulmonary nodules, and serial change on HRCT is unusual.

Sjogren’s syndrome with pulmonary nodular light chain deposition disease; response to mycophenolate mofetile

Light chain deposition disease associated with primary Sjogren’s syndrome has been rarely reported in the medical literature. We report a 65-year old Caucasian woman with Sjogren’s syndrome (SS) for twenty eight years associated with nodular pulmonary light chain deposition disease. This case is unique in the improvement of clinical symptoms and pulmonary function tests following treatment with mycophenolate mofetil (MMF). Primary SS is an automimmune exocrinopathy which is characterized by keratoconjunctivitis sicca and xerostomia. SS is known to be associated with B cell hyperactivity, polyclonal gammopathy and low grade marginal zone B cell lymphoma. Light chain deposition disease is a non-amyloid monoclonal immunoglobulin disorder that is caused by a clonal plasma cell proliferative disorder. Tissue deposits in light chain deposition disease are granular not fibrillar, and do not stain with Congo Red. The coexistence of SS and light chain depositon disease is unusual.

Pulmonary Light and Heavy Chain Deposition Disease

A 64-year-old man with a history of smoking and asbestos exposure was referred for an F-18 FDG PET/CT, to evaluate multiple growing lung nodules that had been found incidentally on prior chest CTs. The PET/CT showed multiple hypermetabolic nodules in both the lungs, with varying intensity of FDG uptake, raising the suspicion of multifocal malignancy. Wedge resections of the right lung were done to remove the 2 most hypermetabolic nodules, and histologic evaluation revealed pulmonary light and heavy chain deposition disease. A follow-up PET/CT performed 1 year later showed another slowly growing nodule in the left lung with a significant increase in F-18 FDG uptake. Only 22 cases of pulmonary light chain deposition disease have been reported in the literature. This is a report of F-18 FDG uptake in nodules of pulmonary light chain deposition disease. These nodules can grow in size and can show increased F-18 FDG uptake on follow-up studies, mimicking a growing lung malignancy.

Pathomechanisms of cyst formation in pulmonary light chain deposition disease

Cystic lung light chain deposition disease (CL-LCDD) is a recently described rare disorder characterised by numerous cysts and diffuse monoclonal nonamyloid light chain deposits surrounded by macrophagic giant cells. The mechanisms responsible for cyst development remain unknown. The objectives of the present study were to analyse the major components of the pulmonary extracellular matrix in CL-LCDD and to determine the influence of metalloproteinases (MMPs) by comparison with other cystic lung disorders. A virtually complete degradation of the elastic network was found in CL-LCDD. To a lesser degree, loss of fibrillar and basement membrane collagens was also observed. Macrophagic giant cells expressed MMP-1, MMP-2, MMP-9, MMP-12 and MMP-14 and in situ zymography highlighted a strong gelatinolytic activity. As in CL-LCDD, cystic lesions in Langerhans' cell histiocytosis (LCH) and lymphangioleiomyomatosis (LAM) were characterised by the lack of elastic fibres. Similarly, MMP were expressed in CL-LCDD and LCH but the labelled cells were different. In contrast, few MMPs were detected in LAM. In conclusion, elastolysis is common to cystic lung light chain deposition disease and other cystic lung disorders, suggesting its implication in cyst formation. Moreover, in cystic lung light chain deposition disease, a role of metalloproteinases in elastolysis is strongly indicated by the metalloproteinase expression and activity pattern.

Pulmonary Light Chain Deposition Disease: Report of Five Cases and Review of the Literature

Pulmonary Light Chain Deposition Disease: Report of Five Cases and Review of the Literature

Pulmonary Light Chain Deposition Disease

Light chain deposition disease (LCDD) in the lung is a rare occurrence. We describe 5 new cases of this entity, review the literature, and compare pulmonary light chain deposits to pulmonary amyloidosis. In addition, we identified 17 patients with pulmonary LCDD in the literature with sufficient clinical information to allow evaluation of clinical presentation, laboratory findings, histologic appearance, and disease progression. In these 22 patients, 2 different histologic patterns were appreciated: diffuse and nodular. A parallel with the diffuse and nodular forms of pulmonary amyloidosis is suggested. The 10 patients with nodular LCDD had an overall better prognosis compared with the 12 patients with diffuse pulmonary LCDD. However, when compared to what is reported in the literature for nodular pulmonary amyloidosis, the patients with nodular LCDD had a higher incidence of an associated lymphoproliferative and/or plasma cell dyscrasia and renal failure. Light chain deposits in the lung are histologically similar to amyloid but are not Congophilic. Their electron microscopic appearance is distinctly different with fibrils in amyloid and granular deposits in LCDD. As the diffuse forms of LCDD and amyloidosis have a similarly poor prognosis, differentiating the 2 entities is probably not critical. However, when present as nodules, LCDD is more frequently associated with an underlying plasma cell dyscrasia or renal failure than is amyloidosis, and therefore the distinction may be clinically important.

Pulmonary Cystic Disorder Related to Light Chain Deposition Disease

Light chain deposition disease (LCDD) is a rare disorder that very uncommonly affects the lung. We report three cases of severe cystic pulmonary LCDD leading to lung transplantation. Such a presentation has never been previously reported. The three patients present with a progressive obstructive pulmonary pattern associated with numerous cysts diffusely distributed in both lungs. The disease was histologically characterized by non-amyloid amorphous deposits in the alveolar walls, the small airways and the vessels. It was associated with emphysematous-like changes and small airway dilation. Monotypic kappa light chain fixation was demonstrated on the abnormal deposits and along the basement membranes. Electron microscopy revealed coarsely granular electron-dense deposits in the same localizations. Mild extrapulmonary deposits were found in salivary glands in one patient. No immunoproliferative disorder was identified. We conclude that LCDD may primarily affect the lung, present as a pulmonary cystic disorder, and lead to severe respiratory insufficiency.