Enhanced immune complex formation in the lungs of patients with dermatomyositis.

BACKGROUND: Interstitial lung disease is frequently comorbid with dermatomyositis and has a poor prognosis, especially in patients with the anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody. However, the pathogenesis of dermatomyositis-related interstitial lung disease remains unclear. METHODS: We examined 18 and 19 patients with dermatomyositis-related interstitial lung disease and idiopathic pulmonary fibrosis (control), respectively. Lung tissues obtained from these patients were semi-quantitatively evaluated by immunohistochemical staining with in-house anti-human MDA5 monoclonal antibodies, as well as anti-human immunoglobulin (Ig) G, IgM, IgA, and complement component 3(C3) antibodies. We established human MDA5 transgenic mice and treated them with rabbit anti-human MDA5 polyclonal antibodies, and evaluated lung injury and Ig and C3 expression. RESULTS: MDA5 was moderately or strongly expressed in the lungs of patients in both groups, with no significant differences between the groups. However, patients with dermatomyositis-related interstitial lung disease showed significantly stronger expression of C3 (p < 0.001), IgG (p < 0.001), and IgM (p = 0.001) in the lungs than control. Moreover, lung C3, but IgG, IgA, nor IgM expression was significantly stronger in MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease (n = 9) than in MDA5 autoantibody-negative dermatomyositis-related interstitial lung disease (n = 9; p = 0.022). Treatment with anti-MDA5 antibodies induced lung injury in MDA5 transgenic mice, and strong immunoglobulin and C3 expression was observed in the lungs of the mice. CONCLUSION: Strong immunoglobulin and C3 expression in the lungs involve lung injury related to dermatomyositis-related interstitial lung disease. Enhanced immune complex formation in the lungs may contribute to the poor prognosis of MDA5 autoantibody-positive dermatomyositis-related interstitial lung disease.

Clinical significance of high monocyte counts for the continuous treatment with nintedanib.

BACKGROUND: Nintedanib is now widely used to treat interstitial lung disease (ILD). Adverse events, which occur in not a few patients, make it difficult to continue nintedanib treatment, but the risk factors for adverse events are not well understood. METHODS: In this retrospective cohort study, we enrolled 111 patients with ILDs treated with nintedanib and investigated the factors involved in starting dosage reduction, withdrawal, or discontinuation within 12 months, even with appropriate symptomatic treatment. We also examined the efficacy of nintedanib in reducing the frequency of acute exacerbations and the prevention of pulmonary function reduction. RESULTS: Patients with high monocyte counts (> 0.454 × 109/L) had a significantly higher frequency of treatment failure, such as dosage reduction, withdrawal, or discontinuation. High monocyte count was as significant a risk factor as body surface area (BSA). Regarding efficacy, there was no difference in the frequency of acute exacerbations or the amount of decline in pulmonary function within 12 months between the normal (300 mg) and reduced (200 mg) starting dosage groups. CONCLUSION: Our study results indicate that patients with higher monocyte counts (> 0.454 × 109/L) should very careful about side effects with regard to nintedanib administration. Like BSA, a higher monocyte count is considered a risk factor for nintedanib treatment failure. There was no difference in FVC decline and frequency of acute exacerbations between the starting doseage of nintedanib, 300 mg and 200 mg. Considering the risk of withdrawal periods and discontinuation, a reduced starting dosage may be acceptable in the patients with higher monocyte counts or small body sizes.

Successful Treatment of a Patient with Drug-Refractory Rheumatoid Arthritis-Associated Interstitial Lung Disease with Upadacitinib: A Case Report.

Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that exhibited favorable response to upadacitinib. A 69-year-old man, former smoker, was diagnosed with RA-ILD based on persistent symmetric polyarthritis, elevated C-reactive protein levels and erythrocyte sedimentation rate, reduced diffusing capacity for carbon monoxide/alveolar volume (DLCO 69.9%), and bilateral ground-glass attenuation with traction bronchiectasis, predominantly in the lower lung lobe. Initial treatment with oral prednisolone and methotrexate was started; however, the patient showed worsening dyspnea, chest high-resolution computed tomography abnormalities, and decreased pulmonary function. The dose of prednisolone was increased, and methotrexate was shifted to tacrolimus; however, tacrolimus was eventually discontinued because of renal dysfunction. Subsequent treatment changes included abatacept followed by intravenous cyclophosphamide, but ILD activity continued to worsen and met the criteria of progressive pulmonary fibrosis. Approximately 4.5 years after the RA diagnosis, dyspnea, radiological abnormalities, and DLCO improved following treatment switch to upadacitinib, one of JAKis. JAKi therapy may have potential as a treatment option for refractory RA-ILD.

Cicatricial organising pneumonia associated with fibrosing interstitial pneumonia - a clinicopathological study.

AIMS: The recent recognition of cicatricial organising pneumonia (ciOP) indicates that the ciOP may resemble or simulate fibrotic interstitial pneumonia; however, there has been great uncertainty regarding the affected populations, pathogenesis, clinical relevance and characteristics. In this study, we compared the characteristics of fibrotic interstitial pneumonia with and without ciOP. METHODS AND RESULTS: We enrolled 121 patients from the consultation archive whose pathological findings were fibrotic interstitial pneumonia and for whom follow-up clinical data were available. We reviewed these cases histopathologically and classified them according to whether or not they showed ciOP. We compared the clinicopathological features between the two groups. CiOP, histopathologically characterised by deposition of dense collagenous fibres within the alveolar space without destruction of the lung structure, was found in 48 patients (39.7%). None of the cases with ciOP experienced acute exacerbation during 12 months' follow-up. The group with ciOP had more severe diffusion impairment but this, together with restrictive ventilatory impairment, improved significantly compared to the group without ciOP. CONCLUSION: CiOP is a histopathological finding commonly found in fibrotic interstitial pneumonia. It does not relate to acute exacerbation or decrease in pulmonary function.

Determining Response to Treatment for Drug-Induced Bronchocentric Granulomatosis by the Forced Oscillation Technique.

Anti-tumor necrosis factor alpha (TNFα) therapy is widely used to treat various inflammatory conditions. Paradoxically, there are several case reports describing the development of bronchocentric granulomatosis treated with TNFα inhibitors, and it is difficult to determine the effect of treatment using conventional spirometry because the lesions are located in small airways. However, it has been reported that the forced oscillation technique (FOT) is useful in the evaluation of small airway disease in bronchial asthma or chronic obstructive pulmonary disease. We performed the FOT to determine the effect of treatment on bronchocentric granulomatosis and found it to be useful. We report the case of a 55-year-old female with ulcerative colitis who was treated with golimumab and who developed bronchocentric granulomatosis as a sarcoid-like reaction to golimumab. She was successfully treated with prednisone, and the treatment efficacy was confirmed by the FOT. The FOT may be useful in the evaluation of small airway disease in bronchocentric granulomatosis. This case may help inform clinicians of the usefulness of the FOT to assess small airway disease in various diseases.

Human immunodeficiency virus-associated vacuolar encephalomyelopathy with granulomatous-lymphocytic interstitial lung disease improved after antiretroviral therapy: a case report.

BACKGROUND: Vacuolar encephalomyelopathy, a disregarded diagnosis lately, was a major neurological disease in the terminal stages of human immunodeficiency virus (HIV)-1 infection in the pre-antiretroviral therapy (ART) era. Granulomatous-lymphocytic interstitial lung disease (GLILD) was classically identified as a non-infectious complication of common variable immunodeficiency; however, it is now being recognized in other immunodeficiency disorders. Here, we report the first case of GLILD accompanied by vacuolar encephalomyelopathy in a newly diagnosed HIV-infected man. CASE PRESENTATION: A 40-year-old Japanese man presented with chronic dry cough and progressing paraplegia. Radiological examination revealed diffuse pulmonary abnormalities in bilateral lungs, focal demyelinating lesions of the spinal cord, and white matter lesions in the brain. He was diagnosed with GLILD based on marked lymphocytosis detecting in bronchoalveolar lavage, and transbronchial-biopsy proven T-cellular interstitial lung disease with granulomas. Microbiological examinations did not reveal an etiologic agent. The patient was also diagnosed with HIV-associated vacuolar encephalomyelopathy on the basis of an elevated HIV viral load in cerebrospinal fluid. After initiating ART, the brain lesions and paraplegia improved significantly, and interstitial abnormalities of the lungs and cough disappeared. CONCLUSION: This report highlights that even in the post-ART era in developed countries with advanced healthcare services, HIV-associated vacuolar encephalomyelopathy should be considered in the differential diagnosis of a progressive neurological disorder during the first visit. Furthermore, GLILD may represent an HIV-associated pulmonary manifestation that can be treated by ART.

Pneumoconiosis with a Sarcoid-Like Reaction Other than Beryllium Exposure: A Case Report and Literature Review.

Background: Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in CBD have occasionally been reported in exposure to dusts of other metals. However, reports describing the clinical, radiographic, and pathological findings in conditions other than beryllium-induced granulomatous lung diseases, and detailed information on mineralogical analyses of metal dusts, are limited. Case presentation: A 51-year-old Japanese man with rapidly progressing nodular shadows on chest radiography, and a 10-year occupation history of underground construction without beryllium exposure, was referred to our hospital. High-resolution computed tomography showed well-defined multiple centrilobular and perilobular nodules, and thickening of the intralobular septa in the middle and lower zones of both lungs. No extrathoracic manifestations were observed. Pathologically, the lung specimens showed 5-12 mm nodules with dust deposition and several non-necrotizing granulomas along the lymphatic routes. X-ray analytical electron microscopy of the same specimens revealed aluminum, iron, titanium, and silica deposition in the lung tissues. The patient stopped smoking and changed his occupation to avoid further dust exposure; the chest radiography shadows decreased 5 years later. Conclusion: The radiological appearances of CBD and sarcoidosis are similar, although mediastinal or hilar lymphadenopathy is less common in CBD and is usually seen in the presence of parenchymal opacities. Extrathoracic manifestations are also rare. Despite limited evidence, these findings are similar to those observed in pneumoconiosis with a sarcoid-like reaction due to exposure to dust other than of beryllium. Aluminum is frequently detected in patients with pneumoconiosis with a sarcoid-like reaction and is listed as an inorganic agent in the etiology of sarcoidosis. It was also detected in our patient and may have contributed to the etiology. Additionally, our case suggests that cessation of dust exposure may contribute to improvement under the aforementioned conditions.

[Ectopic pulmonary calcification after parathyroidectomy in multiple myeloma].

Ectopic soft tissue calcification (ESTC), a rare clinical condition, causes tissue and organ damage. It is associated with chronic renal failure, hyperparathyroidism, and malignant neoplasms, including multiple myeloma, and it is reportedly resistant to treatment. Here, we present the case of a 71-year-old male with multiple myeloma who had rapid ESTC in the lung. He had developed hypoparathyroidism secondary to thyroidectomy. During the course of our observation, he rapidly developed ectopic pulmonary calcification approximately 2 weeks after acquiring an infection. There was no evidence of further progression of multiple myeloma after the onset of ESTC, and treatment with ferric citrate hydrate and precipitated calcium resulted in immediate improvement of his pulmonary signs. We recommend cautious monitoring for patients with multiple myeloma and hypoparathyroidism to detect the onset of ectopic calcification. In addition, low blood phosphorus levels should be effectively treated.

An autopsy case of refractory vasculo-Behçet's disease.

Pulmonary vascular involvement in Behçet's disease is a rare complication with a poor prognosis. We present an autopsy case of vasculo-Behçet's disease complicated by pulmonary hemorrhage, possibly caused by rupture of pulmonary artery aneurysms. The patient was treated with a combination of high-dose steroids and pulse cyclophosphamide, but he died from massive hemoptysis. This case highlights the need for potent new therapies for patients with vasculo-Behçet's disease refractory to conventional immunosuppressive therapy, such as a combination of steroids and cyclophosphamide.

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

OBJECTIVE: The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. METHODS: Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. RESULTS: A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). CONCLUSIONS: The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Feasibility re-evaluation of 75 mg/m² docetaxel in Japanese patients with previously treated non-small cell lung cancer.

OBJECTIVE: The primary objective of this study was to re-evaluate the feasibility of docetaxel at doses of up to 75 mg/m² in Japanese patients with previously treated non-small cell lung cancer. METHODS: Patients received escalated doses of docetaxel at 70 mg/m² (level 1) or 75 mg/m² (level 2) every 3 weeks until disease progression or unacceptable toxicities. Dose escalation was decided on the basis of dose-limiting toxicity in the first cycle of chemotherapy. RESULTS: At dose level 1, dose-limiting toxicity--Grade 3 febrile neutropenia--was observed in one of the six patients and at dose level 2, it was seen in one of the first six patients. Therefore, an additional 14 patients were enrolled at dose level 2, as originally planned. Among the total of 20 patients at dose level 2, 6 (<33%) developed dose-limiting toxicity in the first cycle: febrile neutropenia in 5 and pneumonia in 1. Finally, 10 (50%) of the 20 patients experienced toxicities that met the dose-limiting toxicity criteria, including 8 with febrile neutropenia throughout the treatment period, but this was manageable with dose reduction or appropriate supportive care. Other observed toxicities were predictable from the safety profile of decetaxel and were also well managed. Four partial responses were observed, giving an overall response rate of 15.4%. The median progression-free survival period of the patients overall was 4.0 months (95% confidence interval 1.4-6.6 months). CONCLUSIONS: Although docetaxel administration at an initial dose of 75 mg/m² requires careful attention because of the high incidence of febrile neutropenia, this dose is considered feasible according to the protocol definition in Japanese patients with previously treated non-small cell lung cancer.

Obesity may be a risk factor for transbronchial lung cryobiopsy-related adverse events in Japanese patients with interstitial lung disease.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is known to be associated with a high incidence of adverse events. However, few studies have investigated the correlation between obesity and the risk of TBLC-related adverse events, especially in Asians, who are known to have characteristic differences in height and weight as compared to individuals of other ethnicities. METHODS: We retrospectively assessed 102 Japanese patients who underwent TBLC for the diagnosis of interstitial lung disease to evaluate the correlation between patient characteristics and the occurrence of TBLC-related adverse events (hemorrhage, pneumothorax, and acute exacerbation of interstitial lung disease). RESULTS: TBLC-related adverse events occurred in 19 patients (18.6 %), with hemorrhage being the most common adverse event (in 14 patients, 13.7 %). There was no correlation between age, sex, or pulmonary function test results and the occurrence of adverse events. The body mass index (BMI) cut-off predicting the occurrence of all adverse events was 26.6 kg/m2 (sensitivity of 0.389 and specificity of 0.852), and that predicting the occurrence of adverse events of hemorrhage was 26.8 kg/m2 (sensitivity of 0.462 and specificity of 0.907). Among patients with a BMI >26.8 kg/m2, adverse events of hemorrhage occurred in 37.5 % of cases, which was higher than among those with a BMI <26.8 kg/m2. CONCLUSIONS: Obesity is a risk factor for the incidence of TBLC-related adverse events, particularly adverse events of hemorrhage, in Japanese patients. The BMI cut-off values that predicted an increased frequency of TBLC-related adverse events and hemorrhage specifically were 26.6 and 26.8 kg/m2, respectively.

Soluble form of the MDA5 protein in human sera.

Viral double-stranded RNA (dsRNA) is sensed by toll-like receptor 3 (TLR3) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), including melanoma differentiation-associated gene 5 (MDA5). MDA5 recognizes the genome of dsRNA viruses and replication intermediates of single-stranded RNA viruses. MDA5 also plays an important role in the development of autoimmune diseases, such as Aicardi-Goutieres syndrome and type I diabetes. Patients with dermatomyositis with serum MDA5 autoantibodies (anti-CADM-140) are known to have a high risk of developing rapidly progressive interstitial lung disease and poor prognosis. However, there have been no reports on the soluble form of MDA5 in human serum. In the present study, we generated in-house monoclonal antibodies (mAbs) against human MDA5. We then performed immunohistochemical analysis and sensitive sandwich immunoassays to detect the MDA5 protein using two different mAbs (clones H27 and H46). As per the immunohistochemical analysis, the MDA5 protein was moderately expressed in the alveolar epithelia of normal lungs and was strongly expressed in the cytoplasm of lymphoid cells in the tonsils and acinar cells of the pancreas. Interestingly, soluble MDA5 protein was detectable in the serum, but not in the urine, of healthy donors. Soluble MDA5 protein was also detectable in the serum of patients with dermatomyositis. Immunoblot analysis showed that human cells expressed a 120 kDa MDA5 protein, while the 60 kDa MDA5 protein increased in the supernatant of peripheral mononuclear cells within 15 min after MDA5 agonist/double-strand RNA stimulation. Hydrogen deuterium exchange mass spectrometry revealed that an anti-MDA5 mAb (clone H46) bound to the epitope (415QILENSLLNL424) derived from the helicase domain of MDA5. These results indicate that a soluble MDA5 protein containing the helicase domain of MDA5 could be rapidly released from the cytoplasm of tissues after RNA stimulation.

Clinical significance of interstitial lung abnormalities and immune checkpoint inhibitor-induced interstitial lung disease in patients with non-small cell lung cancer.

BACKGROUND: Interstitial lung abnormalities (ILAs) are known to be a risk of drug-induced pneumonitis. However, there are few reports on the relationship between ILAs and immune checkpoint inhibitor-related interstitial lung disease (ICI-ILD). We retrospectively investigated the clinical significance of ILAs in patients with non-small cell lung cancer (NSCLC) receiving ICIs. METHODS: We defined ILAs as nondependent abnormalities affecting more than 5% of any lung zone, including ground-glass or diffuse centrilobular nodularities, traction bronchiectasis, honeycombing, and nonemphysematous cysts. Early-onset ICI-ILD was defined as developing within 3 months after the initiation of ICI administration. RESULTS: Of 264 patients with advanced NSCLC, 57 patients (21.6%) had ILAs (43 fibrotic and 14 nonfibrotic ILAs). The difference between the incidence of ICI-ILD in patients with or without ILAs was not significant. Of 193 patients treated by ICI monotherapy, 18 (9.3%) developed early-onset ICI-ILD. Among patients receiving ICI monotherapy, the incidence of early-onset ICI-ILD was significantly higher in patients with than in patients without nonfibrotic ILAs. CONCLUSION: The presence of nonfibrotic ILAs is a significant risk for early-onset ICI-ILD in patients with NSCLC undergoing ICI monotherapy. Clinicians should be aware of ILAs, especially nonfibrotic ILAs, before administering ICIs to lung cancer patients.

Acute exacerbation of idiopathic pulmonary fibrosis after bivalent {tozinameran and famtozinameran} mRNA COVID-19 vaccination.

An 82-year-old man diagnosed with interstitial lung disease through computed tomography (CT) 1 year prior received a bivalent (tozinameran and famtozinameran) mRNA COVID-19 vaccine. He developed respiratory symptoms 1.5 months later, and chest high-resolution CT revealed new ground-glass opacities showing traction bronchiectasis. Transbronchial lung cryobiopsy revealed organizing acute lung injury and fibrosis with architectural destruction. The patient was diagnosed with an acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). The bivalent mRNA COVID-19 vaccination was determined as the cause of the AE-IPF based on detailed medical history and examination findings. High-dose corticosteroid therapy improved the patient's symptoms and radiological findings.

A Rare Case of Diffuse Bilateral Minute Pulmonary Meningothelial-like Nodules Increasing over the Short Term and Resembling Metastatic Lung Cancer.

A 54-year-old woman was referred to our hospital because computed tomography (CT) revealed multiple lung nodules during a health checkup. The nodules were up to 5 mm in diameter and randomly distributed in both lungs, appearing ring-shaped. No clinical symptoms were present. However, the nodes proliferated, and multiple lung metastases could not be ruled out, so a biopsy was performed to establish a diagnosis. She was diagnosed with minute pulmonary meningothelial-like nodules (MPMNs), and her condition had not deteriorated at the latest follow-up. Although rare, MPMNs can proliferate for a short time, but a biopsy to exclude malignant causes is essential.

The Characteristic of Transbronchial Lung Cryobiopsy in the Pathological Diagnosis of Hypersensitivity Pneumonitis.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) has widely used for the diagnosis of diffuse lung disease. However, it remains unclear whether TBLC is useful for the diagnosis in hypersensitivity pneumonitis (HP). METHODS: We investigated 18 patients who underwent TBLC and were diagnosed with HP based on pathology or multidisciplinary discussion (MDD). Of the 18 patients, 12 had fibrotic HP (fHP), 2 had non-fibrotic HP (non-fHP) diagnosed with MDD. The remaining 4 patients were diagnosed with fHP by pathology but not by MDD because of clinical features. The radiology and pathology of these cases were compared. RESULTS: All patients with fHP showed radiological findings of inflammation, fibrosis, and airway disease. Conversely, pathology showed fibrosis and inflammation in 11 of 12 cases (92%), but airway disease was significantly less common with 5 cases (42%) (p = 0.014). Non-fHP showed inflammatory cell infiltration mainly in the centrilobule on pathology, which was consistent with radiology. Granulomas were found in 5 patients with HP (36%). In the non-HP group, airway-centered interstitial fibrosis was observed in 3 patients (75%) with pathology. CONCLUSIONS: The pathology with TBLC is difficult to evaluate airway disease of HP. We need to understand this characteristic of TBLC to make a MDD diagnosis of HP.

Effect of the 2020 hypersensitivity pneumonitis guideline on the pathologic diagnosis of interstitial pneumonia.

It was reported that the 2020 guideline for hypersensitivity pneumonitis (HP) might result in the overdiagnosis of fibrotic HP (fHP). fHP and other types of interstitial pneumonias have several overlapping characteristics, and a high diagnostic concordance rate of fHP is rarely obtained. Therefore, we investigated the impact of the 2020 HP guideline on the pathological diagnosis of cases previously diagnosed as interstitial pneumonia. We identified 289 fibrotic interstitial pneumonia cases from 2014 to 2019 and classified them into four categories according to the 2020 HP guideline: typical, probable, and indeterminate for fHP and alternative diagnosis. The original pathological diagnosis of 217 cases were compared to their classification as either typical, probable, or indeterminate for fHP according to the 2020 guideline. The clinical data, including serum data and pulmonary function tests, were compared among the groups. Diagnoses changed from non-fHP to fHP for 54 (25%) of the 217 cases, of which, 8 were typical fHP and 46 were probable fHP. The ratio of typical and probable fHP cases to the total number of VATS cases was significantly lower when using transbronchial lung cryobiopsy (p < 0.001). The clinical data of these cases bore a more remarkable resemblance to those diagnosed as indeterminate for fHP than to those diagnosed as typical or probable. The pathological criteria in the new HP guidelines increase the diagnosis of fHP. However, it is unclear whether this increase leads to overdiagnosis, and requires further investigation. Transbronchial lung cryobiopsy may not be helpful when using the new criteria to impart findings for fHP diagnosis.

Granulomatous Lymphocytic Interstitial Lung Disease in Multiple Myeloma.

An 82-year-old woman complained of recurring cough and shortness of breath and was diagnosed with progressive multiple myeloma (MM). Chest computed tomography (CT) revealed bilateral ground-glass opacity and interlobular septal thickening predominantly in the lower lung zones. Histopathologic findings obtained by a transbronchial lung cryobiopsy (TBLC) revealed alveolitis and granulomas consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). Aggressive chemotherapy for MM contributed to the improvement in respiratory symptoms and abnormal chest CT findings. In cases of MM with lung abnormalities, the possibility of GLILD must be ruled out, and a TBLC should be considered to attain an accurate diagnosis.