[Silent pulmonary shadows].

An elderly woman with a 1-year history of pulmonary shadows was admitted because of intermittent cough and sputum production for 2 months. Chest computed tomography (CT) scans showed bilateral consolidations and ground-glass opacities, with areas of low attenuation inside consolidative opacities on the mediastinal window. Previous history of radiotherapy for nasopharyngeal carcinoma and long-term use of a compound menthol nasal drops provided were important clues to the diagnosis. CT scan-guided needle lung biopsy and bronchoalveolar lavage were performed, and lipid-laden macrophages were confirmed in both bronchoalveolar lavage and lung tissue. Final diagnosis of exogenous lipoid pneumonia was made on the basis of her risk factors for aspiration, history of oil exposure, and classic radiological and histopathological features. Symptoms improved after discontinuation of causative exposure. It is important for clinicians to raise awareness of exogenous lipoid pneumonia and other aspiration lung diseases.

[Diffuse thickening of bronchial walls with multiple nodular mucosal protrusions].

A 58-year-old woman presented with a six-month history of nasal congestion, sore throat and cough, and a five-month history of dyspnea. She had a history of xerostomia for one year. On examination, the bilateral submandibular gland and parotid glands were enlarged. Parotid and anterior cervical lymph nodes were palpable. There were rales in both lungs. The rest of the physical examination was unremarkable. Sialographic analysis showed normal caliber in the main duct, stenosis in secondary ducts, and dilation in the proximal ducts. Minor salivary gland biopsy demonstrated periductal lymphocytic infiltration. Chest computed tomography (CT) showed diffuse thickening of the tracheal and bilateral bronchial walls. Bronchoscopy revealed macroscopic multiple nodules mainly in the trachea and bilateral main bronchus. Endobronchial biopsy showed lymphocytic infiltration in the bronchial submucosa. She was diagnosed with Sjögren's syndrome and treated with glucocorticoids. The dose of prednisone was started at 30 mg/d and tapered gradually. Following treatment, the patient's clinical condition improved dramatically, with shrinkage of the enlarged lymph nodes, bilateral submandibular and parotid glands. A repeated chest CT scan revealed improvement of the tracheal and bilateral bronchial thickening. Multiple nodules in the airway regressed, as evidenced by repeated bronchoscopic examination. The final diagnosis was a large-airway disease associated with Sjögren's syndrome.Among airway diseases in Sjögren's syndrome, peripheral airway diseases including bronchiolitis and bronchiectasis are common; however, central airway lesions in Sjögren's syndrome, especially with macroscopic nodules, are rare. In this case, we demonstrated tracheal and endobronchial nodules in Sjögren's syndrome as determined by clinical features, CT scan, bronchoscopy, and response to therapy.

[Multiple pulmonary nodules with cavity formation].

A 64-year-old female patient was admitted to Beijing Chao-Yang Hospital on February 21, 2023 because of right-sided chest pain for more than 4 years and left-sided chest pain for more than 9 months. She had a past medical history of previous tuberculosis and rheumatoid arthritis. A chest CT in October 2018 revealed multiple pulmonary nodules. A CT-guided biopsy showed no tumors, and adenosine deaminase levels in the pleural effusion were elevated, suggesting a high likelihood of tuberculosis. As a result, anti-tuberculosis treatment was initiated in March 2019. In December 2019, she underwent a right lower lobe resection due to localized hydropneumothorax on the right side. Postoperative pathology unveiled granulomatous inflammation with necrosis. A chest CT in May 2020 showed a significant increase in nodules and cavities. In January 2023, a diagnosis of cryptococcal pneumonia was considered, and she was prescribed oral fluconazole. Finally, the diagnosis of pulmonary rheumatoid nodules was confirmed after a pathological consultation of the postoperative specimen. After one month of treatment with oral prednisone and mycophenolate mofetil, a follow-up chest CT showed improvement. It was recommended that she continue with her current treatment and undergo regular chest CT scans.

[Nontuberculous mycobacteria infection and pulmonary alveolar proteinosis in a patient with hematopoietic defects].

A 28-year-old male with a history of leukopenia was admitted with complaints of fever, cough, and dyspnea for 3 months. Initial work-up identified reduced circulating levels of granulocytes, monocytes, lymphocytes, and NK cells. Computed tomography revealed bilateral reticulonodular opacities and mediastinal lymph node enlargement. Peripheral blood culture and mediastinal lymph node aspiration yielded Mycobacterium avium. Genetic testing revealed a heterozygous germline GATA2 mutation (c.1187G>A, R396Q). Despite standard anti-mycobacterial therapy, the patient's dyspnea worsened and subsequent imaging studies revealed diffuse ground-glass opacification. A transbronchial lung biopsy confirmed the development of pulmonary alveolar proteinosis. Bone marrow transplantation had not been performed due to the unavailability of suitable donors. The disease progressed after whole lung lavage, and the patient died at the age of 31 years from respiratory failure. The current case report emphasized the importance of raising awareness about the rare GATA2 deficiency, which is characterized by hematologic abnormalities, primary immunodeficiency, and pulmonary alveolar proteinosis.

[A case of Cryptococcus gattii pneumonia].

Cryptococcus gattii often causes meningitis, but rarely causes pulmonary infections. Here, we reported a patient with asymptomatic pulmonary cryptococcosis caused by Cryptococcus gattii. The patient presented to the thoracic surgery department with an isolated pulmonary nodule that had been present for three years and underwent a thoracoscopic pulmonary wedge resection. Postoperative pathology was consistent with Cryptococcus gattii infection. Although the incidence of Cryptococcus gattii infection is lower than that of Cryptococcus neoformans, the neurological involvement is common and has severe complications. In this report, the risk factors, symptoms, diagnosis, treatment, and prognosis of Cryptococcus gattii pneumonia were discussed to improve clinical awareness of this disease.

[Complicated lymphatic anomaly: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features, clinical manifestations and different diagnosis of patients with complicated lymphatic anomaly. Methods: The clinical and pathologic data of four patients with complicated lymphatic anomaly diagnosed and treated in Peking Union Medical College Hospital from January 2000 to December 2021 were collected and analyzed. Results: One Gorham-Stout disease case and three generalized lymphatic anomaly cases were included in this cohort. Patients' ages ranged from 7 to 32 years. There were three males and one female. The positions of biopsy included three bone biopsy and one bronchus biopsy. Microscopically, all cases showed diffuse enlarged lymphatic channels. At the same time, osteogenesis was obvious in Gorham-Stout disease case. Radiologically, cortical loss was seen in Gorham-Stout disease, and lytic bone confined to the medullary cavity presented in generalized lymphatic anomaly. The three generalized lymphatic anomaly cases also had coagulopathy, and two had effusion. Conclusions: The histologic feature of complicated lymphatic anomaly was diffuse lymphatic malformation, and the diagnosis depends on clinical and pathologic information. The treatment and prognosis of these diseases are different, and therefore it is necessary to understand their clinical and pathologic features and make the correct diagnosis.

[Commentary on "Diagnostic value of surgical lung biopsies for diffuse parenchymal lung disease: the change of disease spectrum in the past 28 years in a single institution in China"].

In the past 30 years, the diagnosis of diffuse interstitial lung disease (DPLD) in China has made great progress,and the understanding of the disease has been significantly improved. More and more diseases have been diagnosed by combining clinical, laboratory examination and typical high-resolution computed tomography(HRCT). In addition, the application of multidisciplinary discussion increased diagnosis rate, and the number of surgical lung biopsies was on a decreasing trend. However, lung biopsy was still required for some DPLD diseases. Different diseases required different lung biopsy methods. Some diseases with characteristic pathological features can be diagnosed by small biopsy specimens. Transbronchial cryobiopsy has a higher diagnostic rate than traditional bronchoscopic lung biopsy. Overall, the number of lung biopsy for DPLD is relatively low in China, and the development of non-tumor respiratory pathology is relatively lagging behind, and there is still the phenomenon of empirical hormone therapy in clinic. So many aspects on diagnosis and standardized treatment of DPLD still require continuous efforts to improve in the future.

[Bloody sputum with cavitary lesions on chest computed tomography scans: a case report].

This article reported a case of a middle-aged man with a 1-year history of intermittent cough and production of bloody sputum. Serum autoantibodies of the patient were negative. Early in the course of the disease, chest computed tomography (CT) scans showed a nodule in the right middle lung lobe with cavity formation. Surgical resection of the lesion was done with a postoperative pathological diagnosis of inflammatory pseudotumor. No treatment was given and his symptoms recurred with new patches in the right upper lobe. Pathology consultation from another hospital found vasculitis under the microscope and a diagnosis of granulomatosis with polyangiitis was made. His symptoms still worsened after glucocorticoid therapy. Final pathological consultation from Peking Union Medical College Hospital reached a diagnosis of pulmonary actinomycosis. Pulmonary lesions were absorbed after anti-infection treatment. The diagnosis and treatment of this patient provided more data for understanding of the relationship between infection and vasculitis among clinicians and pathologists.

[Hypersensitivity pneumonia diagnosed by excisional lung biopsy: a clinicopathological features of 47 cases].

Objective: To analyze the clinicopathological and immunohistochemical characteristics of the hypersensitivity pneumonia (HP) cases that were diagnosed by excisional lung biopsy, to improve the diagnosis accuracy of HP. Methods: The data of 47 HP cases diagnosed by excisional lung biopsy during the last 20 years were collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2000 to June 2020. The clinicopathological features and the immunohistochemical profiles of CD3, CD4, CD8 and CD20 were analyzed using light microscopy and immunohistochemical stains. Results: The age of the patients ranged from 15 to 68 years, while the ratio of male to female was 22∶25. The main symptoms were shortness of breath and cough, and 32 cases had a history of allergen exposure. Most of the patients had restrictive impaired ventilatory function, and impaired diffusion function. The proportion of lymphocytes in bronchoalveolar lavage fluid (BALF) increased in 85.3%(29/34) of the patients, and the CD4+/CD8+ T cell ratio was not higher than 0.8 in 31.3%(10/32) of the patients. Microscopically, 59.6%(28/47) of the cases showed nonnecrotizing granuloma/giant cells in the stroma, and 40.4% (19/47) of the cases had only giant cells. Ninety-three-point six percent of the cases(44/47) had peribronchiolar metaplasia, while 70.2%(33/47) had focal cell-rich inflammation. Forty-four cases (93.6%, 44/47) had fibrosis, which was manifested as usual interstitial pneumonia-like fibrosis (47.7%, 21 cases), nonspecific interstitial pneumonia-like fibrosis (29.5%, 13 cases), purely peribronchiolar fibrosis (6.8%, 3 cases) and mixed fibrosis (15.9%, 7 cases). Immunohistochemistry showed that CD4+ T cells were fewer than CD8+ T cells in 24 cases (55.8%, 24/43) of HP. Thirty-two HP patients had follow-up data. Among them, 7 patients had improved symptoms, 12 patients were stable, and 13 patients had worsening symptoms. Conclusions: The most common type of HP diagnosed by excisional lung biopsy is chronic HP. The clinical characteristics are long course of disease, restricted ventilation disorder and impaired diffusion function with the increase of lymphocyte proportion in BALF. Nearly 1/3 of the patients have no known history of allergen contact. The degree of fibrosis in HP patients diagnosed by excisional lung biopsy is severe, and the histologic types of fibrosis varies, but the UIP-like and/or NSIP-like fibrosis is most common. The CD4+/CD8+ T cell ratio in lung tissues is less than 1 in more than half of the cases. Pulmonary fibrosis continued to increase in some of the patients with chronic HP, even after treatment.

[The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis].

Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.

[Comparison of clinical and pathological features between severe acute respiratory syndrome and coronavirus disease 2019].

Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) shared similar pathogenetic, clinical and pathological features. Fever and cough were the most common symptoms of both diseases, while myalgia and diarrhea were less common in patients with COVID-19. Acute respiratory distress syndrome (ARDS) was the most severe pulmonary complication that caused high mortality rate. Histologically, diffuse alveolar damage (DAD) was the most characteristic finding in non-survivors with either SARS or COVID-19. Cases of patients died less than 10-14 days of disease duration demonstrated acute-phase DAD, while cases beyond 10-14 days of disease duration exhibited organizing-phase DAD in SARS. Meanwhile, organization and fibrosis were usually accompanied by exudation. Coronavirus was mostly detected in pneumocytes, but less in macrophages and bronchiolar epithelial cells. Hemorrhagic necrosis and lymphocyte depletion were found in lymph nodes and spleen in both SARS and COVID-19, indicating a pathological basis of lymphocytopenia. Thrombosis was commonly observed in small vessels and microvasculaturr in lungs accompanying DAD. Microthrombosis was also found in extrapulmonary organs in COVID-19, that was less reported in SARS. Damages in multiple extrapulmonary organs were observed, but coronavirus was not detected in some of those organs, indicating an alternative mechanism beyond viral infection, such as hypoxemia, ischemia and cytokine storm induced immunological injury. DAD due to viral infection and immunological injury, as well as multi-organ dysfunction and extensive microthrombus formation, brought huge challenge to the management of patients with severe SARS or COVID-19.

[The clinical characteristics of 346 patients with IgG4-related disease].

Objective: To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China. Methods: IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016. All patients were followed-up for more than 6 months. The demographic characteristics, symptoms, organ involvements, laboratory examinations and treatment efficacy were evaluated and analyzed. Results: A total of 346 patients were finally enrolled, including 230 males (66.5%) and 116 females (33.5%). The mean age of disease onset was (53.8±14.2) years old. The mostly common involved organs were lymph nodes (56.4%) and submandibular glands (52.6%). Other affected organs and manifestations included: swelling of the lacrimal glands (46.5%), autoimmune pancreatitis (38.4%), pulmonary involvement (28.0%), sclerosing cholangitis (25.4%), naso-sinusitis (23.4%), parotid gland swelling (21.7%), retroperitoneal fibrosis (19.9%), large arteries involvement (9.5%), kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9%), skin lesions (6.4%). Rare features consisted of thyroid glands, pituitary glands, gastrointestinal tract, pachymeningitis, pericardium, sclerosing mediastinitis and orchitis. The majority of patients had multi-organ involvement, such as 74.3% patients with 3 and more, 18.2% and 7.5% patients with 2 and single organ involvement respectively. The average IgG4-RD responder index (IgG4-RD RI) was 13.21±5.70. History of allergy was found in 172 (49.7%) patients. As to the laboratory tests, elevated serum IgG4 levels were confirmed in 285 (94.1%) patients, which was positively correlated with IgG4-RD RI. There were 33.5% patients receiving monotherapy of glucocorticoid, 52.6% treated with glucocorticoids combined with immunosuppressive agents, 4.9% patients with immunosuppressant only, and 9.0% patients with mild disease not receiving medication. The majority (336, 97.1%) patients improved the above regimens. Conclusion: IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement. The mostly common involved organs include lymph node, submandibular glands, and pancreas. Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

[Clinical and pathological characteristics of Erdheim-Chester disease involving the lungs].

Objective: To explore the clinical manifestations, pathological features, differential diagnosis and gene mutation status in patients with pulmonary involvement of Erdheim-Chester disease (ECD). Methods: The clinical data of 4 cases of Erdheim-Chester disease admitted to Peking Union Medical College Hospital from October 2014 to August 2016 were examined for imaging, microscopic and immunohistochemitry findings, and BRAFV600E mutation. The related literatures were reviewed. Results: Among the 4 cases, there were 3 males and 1 female, aging from 7 to 47 years, and the average age was 34.5 years. They complained of chest tightness, shortness of breath and bone pain. They all had multiple bone lesions, involving the long bones, skulls and vertebrae, and imaging showed increased bone uptake and bone sclerosis. CT scan showed pleural thickening or pleural effusion(4/4), widened lobular septa(3/4), bronchial vascular bundle thickening(3/4), multiple patchy ground glass and solid shadows(4/4), and cystic shadows(1/4). Multiple bone lesions were the main extrapulmonary manifestations. All the cases had multiple bone lesions, involving the long bones, skulls and vertebrae, and showed increased bone uptake and bone sclerosis. Surgical biopsy of the thoracic tissue was performed in all 4 cases (pleural in 1 case, lung in 2, anterior mediastinal mass in 1). Microscopically, the lesion was composed of spindle-shaped fibroblasts and foamy histiocytes enmeshed in reactive fibrous tissue. Lymphocytes and plasma cells were also found. Immunohistochemically, all the histiocytes were positive for CD(68), and none of them expressed CD1a. All cases were detected by real-time quantitative PCR for BRAFV600E gene mutation. Conclusions: The pulmonary involvement of Erdheim-Chester disease is rare, with clinical manifestations of chest tightness, shortness of breath, and some have no obvious respiratory symptoms. Pulmonary involvement in Erdheim-Chester disease has important manifestations, in which foam-like tissue cells with diffuse distribution along the lymphatic enmeshed in reactive fibrous tissue. It should be differentiated from diffuse interstitial lung diseases and metastatic tumors. The clinical features are often manifested as pleural thickening and pleural effusion, with multiple bone sclerosis lesions.BRAFV600E mutation detection is helpful for the diagnosis.

[IgG4 immunohistochemistry in Riedle thyroiditis].

Objective: To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD). Methods: A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections. Results: There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively. Conclusions: With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

[IgG(4)-related disease involving the trachea and paratracheal soft tissue: a case report and literature review].

Objective: To investigate the clinical data of a patient with IgG(4)-related disease involving the trachea and paratracheal soft tissue and review the literature so as to improve the understanding level of the disorder. Methods: To analyze the clinical manifestation, laboratory examination, imaging, histopathology, treatment and prognosis of a patient with IgG(4)-related disease trachea and paratracheal soft tissue involved, who was admitted to the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital. The relevant literatures were reviewed. Results: A 18-year-old female was admitted with chief complaint of cough, dyspnea, and neck mass. Neck CT suggested that tracheal stenosis was caused by surrounded soft tissue. Paratracheal mass biopsy showed dense collagen fibers with infiltration of many lymphocytes and plasma cells. Immunohistochemical stain found that IgG(4)-positive plasma cells were >50/high power field (HPF) and a ratio of IgG(4)/IgG positive cells was over 40% .The level of serum IgG(4) was significantly increased (2 930 mg/L). She was diagnosed as IgG(4)-related disease. The patient was treated with 80 mg intravenous methylprednisolone per day for three days, then prednisone 40 mg daily oral. Her dyspnea was significantly relieved.One month later, CT scan showed that the cervical tracheal stenosis was significantly improved. We identified 20 cases of IgG(4)-related disease involving the trachea and paratracheal soft tissue from databases, in which only 1 case was similar as this patient. The other 19 cases were of extratracheal involvement. Elevated serum IgG(4) was detected in 11/12 patients. Most patients were treated with glucocorticoid, some combined with immunosuppressive agents and rituximab. The clinical outcome was good. Conclusion: IgG(4)-related disease involving the trachea and paratracheal soft tissue is a rare condition. Serum IgG(4) level and histopathology should be considered for diagnosis. Glucocorticoid is effective.