Pathological changes and diagnostic difficulties of hypersensitivity pneumonia / 中国实用内科杂志

Hypersensitivity pneumonia(HP) is one of the rare interstitial lung diseases. The diagnosis, especially the diagnosis of chronic hypersensitivity pneumonia(CHP), has great challenges in clinical, imaging and pathological aspects. In the history of the disease, CHP presents diversity and complexity, and about half of the patients lack diagnostic granuloma, and fibrosis types exist in many forms, such as usual interstitial pneumonia-like fibrosis, nonspecific interstitial pneumonia-like fibrosis, bridging fibrosis or peribronchiolar fibrosis. So HP needs to be differentiated from multiple diseases. In this study, the pathological changes and diagnostic difficulties of HP are summarized and reviewed.

IgG4-related disease involving the trachea and paratracheal soft tissue:a case report and literature review / 中华内科杂志

Objective To investigate the clinical data of a patient with IgG4-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 IgG4-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 IgG4-positive plasma cells were ＞ 50/high power field (HPF) and a ratio of IgG4/IgG positive cells was over 40％.The level of serum IgG4 was significantly increased (2 930 mg/L).She was diagnosed as IgG4-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 IgG4-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 IgG4 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 IgG4-related disease involving the trachea and paratracheal soft tissue is a rare condition.Serum IgG4 level and histopathology should be considered for diagnosis.Glucocorticoid is effective.

Computed Tomographic and Pathological Features of Primary Pulmonary Sarcomatoid Carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the computed tomographic (CT) and pathological features of primary pulmonary sarcomatoid carcinoma (PSC).</p><p><b>METHODS</b>The clinical data and CT images of 20 patients with pathologically confirmed PSC were retrospectively analyzed.</p><p><b>RESULTS</b>Solitary pulmonary mass was identified in 18 patients and multiple pulmonary masses in 2 patients, amounting to 22 masses. There were 17 peripheral masses and 5 central masses, including 11 masses larger than 5 cm. The smooth margin was identified in 9 masses, deep lobulation and/or spinous protuberance in 11 masses, and ill-defined margin in 2 masses. Pleural indentation was identified in 2 masses and pleural thickening with wide basement was identified in 14 masses. On plain CT, cavity was observed in 5 masses, hypo-density in 7 masses, and homogeneous density in 10 masses. On contrast-enhanced CT scanning, irregular ring/patchy enhancement were shown in 15 masses and slightly homogenous enhancement in 2 masses. Of all patients, 6 patients had unilateral or bilateral hilar and/or mediastinal lymphadenopathy. There were 16 pleomorphic carcinomas and 4 spindle cell carcinomas. Immunohistochemically, anti-pan cytokeratin antibody was positive in 13 patients, cytokeratin was positive in 8 patients, Vimentin was positive in 15 patients, epithelial membrane antigen was positive in 1 patient, and thyroid transcription factor-1 was positive in 8 patients.</p><p><b>CONCLUSION</b>PSC has some specific CT features; however, the final confirmation of PSC still depends on pathological and immunohistochemical examinations.</p>

Types of Organ Involvement in Patients with Immunoglobulin G4-related Disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized systemic disease that can involve multiple organs and various clinical phenotypes. The purpose of this study was to analyze different types of organ involvement in IgG4-RD patients in China.</p><p><b>METHODS</b>We conducted a prospective cohort study on IgG4-RD patients to analyze the clinical manifestations and rare features of IgG4-RD. Patients were grouped into different types according to organ involvement regarding organ number and organ site. The constituent ratio in different types was also analyzed.</p><p><b>RESULTS</b>A total of 200 IgG4-RD patients, with a male:female ratio of 2.08:1, were grouped into different types. Cases having involvement of two or three organs were the most common whereas the fewest number of patients had multi-organ (≥4) involvement. Serum IgG4 and IgE levels, IgG4/IgG ratio, and percentage of eosinophils increased as the number of involved organs increased. In addition, constituent ratio analysis revealed that patients with salivary gland/lacrimal gland swelling, who also constituted the largest number of IgG4-RD patients, had higher serum IgG4 concentrations and IgG4/IgG values, had higher percentage of Eos, and were more likely to have had a history of allergies relative to patients with internal organ involvement.</p><p><b>CONCLUSIONS</b>The characteristic feature of IgG4-RD is multiple organ involvement with various clinical manifestations and different types. Although serum IgG4 levels increased with the number of involved organs, serum IgG4 levels were higher for those patients with salivary gland/lacrimal gland swelling compared with those with internal organ involvement. Thus, valuable clues to the differential diagnosis of IgG4-RD could be obtained by examining the clinical patterns of organ involvement.</p>

Clinical and imaging manifestations of pulmonary mucosa-associated lymphoid tissue lymphoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical and computed tomography (CT) appearances of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma.</p><p><b>METHODS</b>The CT findings and clinical data of 13 patients with pathologically proven pulmonary MALT lymphoma were retrospectively reviewed.</p><p><b>RESULTS</b>Among these 13 patients, seven presented no notable abnormalities, six manifested respiratory symptoms including cough, expectoration, and dyspnea; one of these six patients experienced fever. Chest CT showed solitary nodule in 2 patients and multiple nodules in 3 patients; meanwhile, it showed solitary consolidation in 3 patients and multiple consolidations in 5 patients. Other CT findings included air bronchogram (n = 13), airway dilatation (n = 4), ground glass opacities (n = 5), and interstitial changes (n = 5). One patient had mediastinal lymphoadenopathy and 2 had pleural effusion. Pathology showed massive lymphocyte infiltration; cells with notable nuclear atypia were also seen, which were generated from B cells.</p><p><b>CONCLUSIONS</b>The main CT findings of pulmonary MALT lymphoma include nodules, mass or patchy consolidations with air brochogram; hilar and mediastinal lymphadenopathies are rare. Clinical diagnosis should also be based on pathological findings and immunohistochemical results.</p>

Pathological and high resolution CT findings in Churg-Strauss syndrome / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the Churg-Strauss syndrome (CSS) associated lung involvement, concentrating on clinical characteristics, pathological findings of lung involvements, response to treatment, and prognosis.</p><p><b>METHODS</b>We retrospectively analyzed the characters of the clinical manifestations, thin-section CT and pathological findings of CSS. The study involved 16 patients. Clinical data were obtained by chart review. All patients underwent transbronchial lung biopsy (TBLB). Six of them underwent surgical lung biopsy as well.</p><p><b>RESULTS</b>The patients included 7 men and 9 women, aged from 14 to 61 years (median, 47.5 years). Extrathoracic organs involved included nervous system (7/16) and skin (5/16). Respiratory symptoms included cough (12/16), exertional dyspnea (11/16), hemoptysis (4/16), and chest pain (3/16). CT findings included bilateral ground-glass opacities (12/16), bilateral patchy opacities (12/16), and centrilobular nodules (6/16). The pathological findings of TBLB demonstrated increased eosinophils (3/16), vasculitis (3/16), and interstitial pneumonia (16/16). The pathological findings of surgical lung biopsy of 6 cases showed necrotizing vasculitis in 4 cases, capillaries in 5, eosinophilic pneumonia in 3, granulomas in 2, and airway abnormalities in 3. All patients improved in symptoms after therapy during the study period (range, 3 to 51 months; median, 15 months).</p><p><b>CONCLUSIONS</b>Asthma may be present in CSS patient when there is bronchial involvement. Ground-glass opacities and consolidation seen on high-resolution CT reflect the presence of eosinophilic pneumonia, vasculitis, and pulmonary alveolar hemorrhage. TBLB has significant limitations for the diagnosis of CSS. Early diagnosis and therapy can result in satisfactory prognosis.</p>

Pulmonary lymphomatoid granulomatosis: an immunohistochemical and gene rearrangement study / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the immunophenotype and gene rearrangement pattern of pulmonary lymphomatoid granulomatosis.</p><p><b>METHODS</b>Nine cases of pulmonary lymphomatoid granulomatosis, included 5 cases of open lung biopsy, 3 cases of lobectomy specimen and 1 case of autopsy, were retrospectively analyzed by immunohistochemistry, in-situ hybridization for Epstein-Barr virus-encoded RNA, immunoglobulin and T-cell receptor gene rearrangement studies.</p><p><b>RESULTS</b>The age of patients ranged from 3 to 59 years. The male-to-female ratio was 3: 6. Histologically, all cases showed lymphocytic infiltration surrounding the blood vessels and in the perivascular areas. Most of these lymphoid cells expressed T-cell marker CD3. There were also variable numbers of CD20-positive B cells. The staining for CD56 was negative. According to the WHO classification, there were 4 cases of grade I , 1 case of grade II and 4 cases of grade III lesions. Six cases had gene rearrangement studies performed and 3 of them demonstrated clonal immunoglobulin gene rearrangement (including 1 of the grade II and 2 of the grade III lesions). No T-cell receptor gene rearrangement was detected.</p><p><b>CONCLUSIONS</b>Pulmonary lymphomatoid granulomatosis may represent a heterogeneous group of lymphoproliferative disorders. Some of the cases show B-cell immunophenotype and clonal immunoglobulin gene rearrangement, especially the grade II and grade lesions. They are likely of lymphomatous nature.</p>

Pathologic study of diffuse pulmonary interstitial fibrosis caused by chronic hypersensitivity pneumonitis / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the pathologic characteristics of chronic hypersensitivity pneumonitis, especially the pattern of pulmonary interstitial fibrosis; and to compare the histologic features with those of idiopathic interstitial pneumonitis.</p><p><b>METHODS</b>The HE-stained paraffin sections of 10 cases of chronic hypersensitivity pneumonitis encountered during the period from 2000 to 2008 were retrospectively analyzed.</p><p><b>RESULTS</b>There were altogether 6 males and 4 females, with age of patients ranging from 23 to 59 years (mean=47.2 years). Clinically, the patients presented with chronic cough and shortness of breath for 4 months to 6 years. Histologically, 7 cases showed usual interstitial pneumonitis (UIP)-like fibrosis. Patchy fibrosis was observed under the pleura, adjacent to interlobular septa and around bronchioles. In all of the 7 cases, foci of fibroblastic proliferation, as well as bronchiolar metaplasia of peribronchiolar alveoli and mild bronchiolitis, were noted. Three cases presented with mild honeycomb changes of lung and 3 cases showed non-specific interstitial pneumonitis (NSIP)-like fibrosis, in which the alveolar septa were expanded by fibrous tissue and collagen, with relative preservation of alveolar architecture. Bronchiolitis and lymphocytic infiltrates in alveolar septa were seen. Schaumann bodies were identified in 1 case. In general, patients with chronic hypersensitivity pneumonitis were younger than patients with idiopathic UIP. Computed tomography often showed upper and middle lobar involvement and mosaic attenuation. Compared with idiopathic UIP, the UIP-like fibrosis of chronic hypersensitivity pneumonitis often occurred not only under the pleura and adjacent to interlobular septa, but also around bronchioles and was accompanied by bronchiolar metaplasia.</p><p><b>CONCLUSIONS</b>Chronic hypersensitivity pneumonitis can mimic other types of lung conditions with interstitial fibrosis, especially UIP and NSIP. As a result, some cases of chronic hypersensitivity pneumonitis may be misdiagnosed as such.</p>

Clinical features and prognosis in 21 patients with extrinsic allergic alveolitis / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis (EAA).</p><p><b>METHODS</b>Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases (acute, subacute, and chronic) according to clinical presentations. Follow-up data regarding treatment response, subsequent radiological and pulmonary function studies, and clinical outcomes were collected.</p><p><b>RESULTS</b>A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds (6 cases, 28.6%). The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity (12 cases, 63.2%). The most common findings on high-resolution computed tomography (HRCT) were ground-glass opacities (13 cases, 68.4%) and centrilobular nodules (8 cases, 42.1%). Airway obstruction in pulmonary function test, emphysema, lung cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid (BALF) showed lymphocytosis. The total cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients (P<0.05). Nonnecrotizing granulomas were seen in 8 (47.1%) cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with available follow-up data. Five patients recurred.</p><p><b>CONCLUSIONS</b>The characteristic abnormalities of pulmonary function, findings on HRCT, and pathology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.</p>

Clinicopathologic study of Churg-Strauss syndrome / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and pathologic features of Churg-Strauss syndrome (CCS).</p><p><b>METHODS</b>Three cases of Churg-Strauss syndrome, including 1 autopsy case and 2 cases with open thoracoscopic lung biopsy, were retrospectively reviewed. All the tissue samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin.</p><p><b>RESULTS</b>The first patient was a 68-year-old man who had history of asthma for 4 years, with recent exacerbation and chest pain for 2 weeks. Patient died 1 day after admission due to myocarditis and myocardial infarction. He did not have peripheral eosinophilia, skin or paranasal sinus pathology. CSS represented an incidental autopsy finding and he had never been treated with corticosteroid before. The other 2 patients were a 58-year-old male and a 12-year-old female, respectively. Both had history of asthma, peripheral eosinophilia and lung consolidations on computed tomographic examination. Pathologically, all cases showed vasculitis, perivascular allergic-type granulomas, eosinophilic pneumonia and asthmatic bronchitis.</p><p><b>CONCLUSIONS</b>Thorough understanding of the clinical and pathologic criteria is essential for arriving at a correct diagnosis of CSS. Although some patients may present with atypical symptoms, lung biopsies often reveal the classic histologic findings which include vasculitis and perivascular allergic granuloma formation.</p>

Clinicopathologic study of primary marginal zone B-cell lymphoma of MALT type and lymphoid hyperplasia of lung / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features, immunohistochemical findings and immunoglobulin heavy chain (IgH) gene rearrangement results of primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) and reactive lymphoid hyperplasia.</p><p><b>METHODS</b>Twenty cases, included 13 cases of pulmonary MALToma and 7 cases of pulmonary lymphoid hyperplasia, encountered during the period from 1989 to 2007, were retrospectively analyzed. The samples were paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study and semi-nested polymerase chain reaction for IgH gene rearrangement were performed.</p><p><b>RESULTS</b>The 13 cases of primary pulmonary MALToma were composed of a spectrum of lymphoid cells, including lymphocyte-like cells, centrocyte-like cells and mononuclear B cells with plasmacytoid differentiation. They often had diffuse or marginal zone growth patterns. Lymphoid follicles with neoplastic colonization were apparent. The lymphoma cells spread along alveolar septa and bronchovascular bundles. Vascular invasion was noted in 9 cases, pleura involvement in 6 cases and nodal involvement in 2 cases. Lymphoepithelial lesions (LEL) were identified in 9 cases of pulmonary MALToma. Immunohistochemically, the lymphocytes in LEL were CD20-positive and CD3-negative. On the other hand, LEL was also present in 2 of the 7 cases of lymphoid hyperplasia studied, with a mixture of CD20-positive B cells and CD3-negative T cells. Eight of the 9 cases of primary pulmonary MALToma were positive for IgH gene rearrangement, while all of the 7 cases of lymphoid hyperplasia were negative.</p><p><b>CONCLUSIONS</b>Histologically, the cell population of primary pulmonary MALToma is similar to that of extranodal MALToma occurring in other organs. LEL, though commonly observed in pulmonary MALToma, are not specific and can also be seen in cases of reactive lymphoid hyperplasia. The immunophenotype of intraepithelial lymphocytes in pulmonary MALToma and reactive lymphoid hyperplasia is different. The presence of a monotonous population of CD20-positive intraepithelial lymphocytes supports a diagnosis of MALToma. IgH gene rearrangement study is also useful in differentiating both entities.</p>

Clinicopathologic and immunohistochemical study of pulmonary epithelioid hemangioendothelioma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinical and pathological characteristics of pulmonary epithelioid hemangioendothelioma.</p><p><b>METHODS</b>Four cases of pulmonary epithelioid hemangioendothelioma were studied by histopathologic and immunohistochemical examination of lung biopsy specimens.</p><p><b>RESULTS</b>There were 3 female and 1 male, age 28 to 40 years. Clinically the tumor presented as multiple bilateral small nodules in the lung. Histologically, crown-like clusters of epithelioid tumor cells were obtained which filled in the alveoli locating at the periphery of the tumor nodules, while the central part of the nodules contained myxoid to hyaline matrix. The overall architecture of the lung was still preserved. Additionally, intracytoplasmic vacuoles were seen in tumor cells within which red blood cells were sometimes identified. Tumor cells generally lacked pleomorphism, mitotic activity and necrosis. They were immunohistochemically positive for CD31 and CD34. AE1/AE3 staining was positive in some cases.</p><p><b>CONCLUSIONS</b>Pulmonary epithelioid hemangioendothelioma often occurs in a middle-aged woman and represents a distinct clinical pathological entity.</p>

Clinicopathologic study of 10 cases of osteomalacia or rickets-associated mesenchymal tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features of osteomalacia or rickets-associated mesenchymal tumors.</p><p><b>METHODS</b>The clinical and pathologic findings of 10 cases of osteomalacia or rickets-associated mesenchymal tumors were evaluated. Hematoxylin and eosin stain, immunohistochemistry and histochemistry were performed on the archival paraffin sections.</p><p><b>RESULTS</b>Amongst the 10 patients studied, 6 were males and 4 were females. Their age at the time of operation ranged from 28 to 69 years ( mean = 45.6 years). A history of long-standing bone pain, arthralgia, limitation in movement, hypophosphatemia and hyperphosphaturia was present in all cases. The duration of symptoms ranged from 2 to 27 years (mean = 9.6 years). The tumor size ranged from 1 to 7 cm (mean size = 3.52 cm). Microscopically, the tumors were composed of various mesenchymal cells, including spindled fibroblast-like cells, adipocytes, chondroid cells and mucinous cells. The background was rich in blood vessels. In 8 of the 10 cases, there was also dystrophic calcification in an unusual flocculent or "grungy" pattern. Peripheral woven bone shell formation was noted in 2 cases and non-urate crystal deposition in 2 cases. Mitotic figures were rare in 9 cases. In 1 of the 10 cases however, mitotic figures and bizarre cells were commonly encountered. On immunohistochemical study, the tumor cells were all positive for vimentin. There was focal positivity for smooth muscle actin and CD34 in 5 and 3 cases respectively. The staining for desmin, S-100 and AE1/AE3 was negative. Ki-67 proliferation index was less than 4% in 8 cases and 30% in 1 case. Alcian blue-positive mucinous matrix and mucinous degeneration around vessels were noted in 8 cases.</p><p><b>CONCLUSIONS</b>Most of the osteomalacia or rickets-associated tumors are either benign or low-grade malignant mesenchymal tumors. They can be mistaken as other neoplasms due to the morphologic heterogeneity present. Thorough understanding of the associated clinical features and laboratory investigation results is helpful in arriving at the correct diagnosis.</p>