Serum Calcium and Risk of Nonmedullary Thyroid Cancer in Patients with Primary Hyperparathyroidism.

BACKGROUND Clinical cases of nonmedullary thyroid carcinoma (NMTC) in combination with primary hyperparathyroidism (PHPT) have been reported occasionally. However, the clinical characteristics and risk factors of concomitant NMTC in PHPT patients remain unclear. This study aimed to assess the association between PHPT and NMTC, and evaluate the clinical characteristics and risk factors of NMTC in Chinese patients with PHPT. MATERIAL AND METHODS This was a retrospective cohort analysis. We reviewed the medical records of 155 patients who underwent surgery for PHPT in two large medical centers in China between 2009 and 2014. The clinical manifestations, biochemical abnormalities, and histological characteristics of PHPT patients were analyzed. RESULTS Of the 155 patients with PHPT, 58 patients (37.4%) had thyroid nodules and 12 patients (7.7%) were ill with concomitant NMTC. PHPT patients with NMTC demonstrated significantly lower preoperative serum calcium levels compared to PHPT patients with benign thyroid nodules (p<0.05). A significantly negative association between preoperative serum calcium levels and the presence of NMTC was found in PHPT patients (p<0.05). Furthermore, ROC analysis revealed that albumin-corrected serum calcium levels <2.67 mmol/L had good capacity to differentiate the PHPT patients with NMTC from those with benign thyroid nodules. CONCLUSIONS Compared with the reported much lower prevalence of thyroid carcinoma in the general population, our results suggest that PHPT might be a risk factor for the malignancy of thyroid nodules; a lower level of serum calcium may predict the existence of NMTC in PHPT patients with thyroid nodules.

[Effect of Wnt signaling suppression on gefitinib in non small cell lung cancer cell lines].

OBJECTIVE: To explore the effect of Wnt signaling suppression on proliferation of non small cell lung cancer to gefitinib, and its related mechanisms. METHODS: PC9 and PC9/AB2 cells of both gefitinib sensitive and resistant were treated with different concentrations of gefitinib, and the proliferation index was measured using CCK8 kit. The members of Wnt signaling pathway were detected by Western blot. Dual luciferase reportor gene assay (TOP Flash) was used to document the transcriptional level of ß-catenin. ß-catenin siRNA was transfected into PC9/AB2 cells to suppress the Wnt signaling transcription, followed by treatment with different concentrations of gefitinib. Western blot was then used to detect the expression of EGFR and its downstream signaling after inhibit the expression of ß-catenin. RESULTS: Treating with different concentrations of gefitinib, the resistance of PC9/AB2 cells to gefitinib was significantly increased (P < 0.05). The members of Wnt signaling expressed at higher level in PC9/AB2 cells than in PC9 cells (t = 24.590, P = 0.000). TOP Flash examination showed that the endogenous transcriptional activity of Wnt signaling was higher in PC9/AB2 cell than that in PC9 cell (t = 4.983, P = 0.008). Compared with the negative control group, apoptotic rate and sensitivity to gefitinib significantly increased in interfered group (P < 0.05). The expression of p-ERK1/2 significantly decreased after Wnt signaling suppression, although other proteins showed no significant alterations. CONCLUSION: Suppressing the activity of Wnt signaling can partly reverse the celluar resistance to gefitinib in non small cell lung cancer.

[Effects of 1, 25 (OH)2D3 on bleomycin-induced pulmonary fibrosis in mice].

OBJECTIVE: To observe the effects of 1, 25(OH)2D3 on bleomycin-induced pulmonary fibrosis in mice and to explore its mechanisms. METHODS: Ninety male C57BL/6 mice, 6 to 8 weeks old, were randomly divided into 3 groups according to the table of random numbers: a control group, a model group and a treatment group(n = 30 each). Bleomycin was injected to the mice in the latter 2 groups by single intratracheal injection to duplicate the pulmonary fibrosis model, while the control group was injected with saline. From the next day, the mice in the treatment group received 1, 25 (OH) 2D3 (0.5 µg·kg(-1)·d(-1)) diluted in olive oil by gavage daily, while the other groups were treated with equivalent olive oil. Ten mice in each group were killed randomly on day 14, 21 and 28 after surgery respectively. Pulmonary alveolitis and fibrosis were evaluated by using hematoxylin-eosin and Masson stain method. The content of hydroxyproline was measured by acid hydrolysis method. The mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, and Wnt7a in the lung tissues were measured by real-time RT-PCR, while the protein expression of α-SMA and ß-catenin were assessed by immunohistochemistry. RESULTS: Pulmonary alveolitis at day 14, 21 and fibrosis at day14, 21, 28 in the treatment group were remarkably reduced compared to the model group (all P < 0.05). Compared with the model group, the treatment group showed decreased content of hydroxyproline, decreased mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4 and decreased protein expression of α-SMA and ß-catenin at the 3 time points (all P < 0.05). The content of hydroxyproline and the mRNA levels of collagen1α1, α-SMA, Wnt3a, Wnt4, Wnt7a in the treatment group at 28 d were 0.67 ± 0.14, 1.66 ± 0.34, 1.37 ± 0.41, 1.43 ± 0.27, 1.29 ± 0.19, 1.18 ± 0.20, respectively, all of which were significantly lower than those in the model group (1.10 ± 0.16, 3.50 ± 0.74, 2.68 ± 0.61, 2.60 ± 0.58, 2.23 ± 0.45, 1.93 ± 0.36, respectively). Protein expression of α-SMA and ß-catenin in the treatment group were 0.44 ± 0.13 and 0.25 ± 0.05, respectively, which were also significantly lower than those of the model group(0.98 ± 0.20, 0.58 ± 0.06, respectively). CONCLUSION: 1, 25 (OH) 2D3 was shown to reduce pulmonary fibrosis induced by bleomycin in mice, and its mechanisms might be associated with Wnt signaling suppression.

[The ultrastructural features of sputum deposition and its value in the diagnosis of pulmonary alveolar proteinosis].

OBJECTIVE: To investigate the ultrastructural features of sputum deposition (SD) and its value in the diagnosis of pulmonary alveolar proteinosis (PAP). METHODS: Seven patients with PAP diagnosed by lung biopsy and cytology were enrolled in this study. The patients consisted of 5 men and 2 women, whose median age was 48 years (range 36 to 73). SD and bronchoalveolar lavage fluid (BALF) sediment were made into ultrathin sections and observed under transmission electron microscope (TEM), respectively. Seven cases of control group composed of 4 men and 3 women whose median age was 49 years (range 39 to 68) including 3 cases of bacterial pneumonia, two cases of COPD and 2 cases of exudative pulmonary tuberculosis. Each SD was made into ultrathin section, and compared with the experimental group. RESULTS: In PAP group, Periodic acid-schiff (PAS) staining was performed on 7 sputum smears and none of them was tested positive for any components with diagnostic interest. Four cases from the 7 paraffin-embed sections of BALF sediment by microscopic examination suggested PAP. Under TEM, BALF sediment showed that many lamellar bodies existed in and outside alveolar epithelial cells, and 5 specimens were consistent with PAP diagnosis. Compared with BALF sediment, SD had apparent degeneration with more myelin phagosomes in the cytoplasm of macrophages, more lamellar bodies in alveolar epithelial cells, and lots of lamellar bodies in the shape of concentric circle in the extracellular spaces. Four from the 7 SD samples were consistent with the diagnosis of PAP. No significant difference was found between SD and BALF in the diagnosis of PAP by electronic examination (P > 0.05). In the 7 cases of control group no drifting osmiophilic lamellar bodies in extracellular space were detected. CONCLUSIONS: The osmiophilic lamellar bodies with diagnostic value were found in SD and BALF of patients with PAP. TEM of SD in combination with clinical manifestations and radiologic findings can make a definitive diagnosis of PAP, especially for those patients who have contraindications to lung biopsy and lung lavage.

[A study on the efficacy of glucocorticoid therapy for idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the efficacy of glucocorticoid therapy in idiopathic nonspecific interstitial pneumonia (INSIP). METHODS: Twenty-nine cases of INSIP confirmed by clinical- radiological-pathological (CRP) diagnosis were collected and classified into 2 groups according to the degree of fibrosis: INSIP-1 (including 9 cases of cellular type) and INSIP-2 (20 cases of mixed and fibrotic type). Thirty cases of usual interstitial pneumonia (UIP) confirmed by CRP diagnosis served as the control. Clinical and pathological features, therapeutic effects of glucocorticoids and the follow-up results were retrospectively analyzed and the survival curves were evaluated by Kaplan-Meier method. RESULTS: The mean age at onset of INSIP-1 group [(48 ± 5) years] was significantly younger than INSIP-2 group [(52 ± 11) years] and the UIP group [(57 ± 14) years]. The course of disease in INSIP-1 group [(60 ± 28) months] was longer than that in INSIP-2 group [(48 ± 33) months] and that in the UIP group [(44 ± 23) months], but the differences were not statistically significant (F = 1.22, all P > 0.05). The efficacy rate of glucocorticoid treatment in INSIP-1 group (9/9) was higher than that in INSIP-2 group (11/20) and that in the UIP group (2/30), the differences being statistically significant (all P < 0.05). The follow-up period for INSIP-1 group [(56 ± 27) months] was significantly longer than for INSIP-2 group [(23 ± 18) months] and for the UIP group [(25 ± 17) months], and the rate of significant improvement (6/9) was higher than that of the INSIP-2 group (9/20) and the UIP group (0/30), the differences being statistically significant (F = 9.224, all P < 0.05). The mortality of INSIP-1 group (0/9) was lower than that in INSIP-2 group (4/20) and the UIP group (16/30), the difference being statistically significant (exact probability value 0.000 - 0.005, P < 0.05). CONCLUSIONS: The degree of fibrosis of INSIP is closely correlated with the effect of glucocorticoid therapy and prognosis. The cellular type has a favorable reaction to glucocorticoid therapy and a better prognosis as compared to the fibrotic type.

Estrogen-Induced Stromal FGF18 Promotes Proliferation and Invasion of Endometrial Carcinoma Cells Through ERK and Akt Signaling.

OBJECTIVE: The aim of this study was to evaluate whether estrogen promoted the proliferation and invasion of endometrial carcinoma (EC) cells through paracrine FGFs in endometrial stromal cells (ESCs). PATIENTS AND METHODS: We screened gene alterations in a primary ESC culture after 10 nM estrogen treatment using an Agilent mRNA microarray. We knocked down stromal FGF18 expression in a co-culture system and aimed to explore the contribution of E2-induced stromal FGF18 to the proliferation and invasion of EC cells. To determine the effective receptors and detailed downstream signaling of FGF18, we co-cultured estrogen-treated hESCs with FGFR1-, FGFR2-, FGFR3- or FGFR4-knockdown Ishikawa cells. Finally, we detected FGF18 expression in clinical samples, including several primary cultures of different ESCs and a series of tissue microarrays (TMAs) of 90 patients with EC. RESULTS: A few genes altered significantly in estrogen-treated primary ESCs, but only FGF18 was noticeably enhanced among the FGF family genes. Knockdown of FGF18 expression in hESCs inhibited the promoting effect of FGF18 on the proliferation and invasion of EC cells. FGF18 bound FGFR2 and FGFR3 in Ishikawa cells to activate downstream ERK and Akt pathways and to promote the viability of EC cells. The FGF18-FGFR2 and FGF18-FGFR3 pathways had close correlations with Survivin and CD44V6 expression but not with P53. Primary ESCs of endometrioid EC (EEC, type I EC) had higher FGF18 expression than ESCs of normal endometrium (NE), endometrial atypical hyperplasia (EAH) and type II EC. CONCLUSION: Estrogen induced FGF18 in ESCs to promote the proliferation and invasion of EC cells, and FGFR inhibitors should be considered as promising candidate targets for EC treatment.

[Idiopathic lymphoid interstitial pneumonia: a report of 3 cases and literature review].

OBJECTIVE: To analyze the clinical, radiological and pathological characteristics of idiopathic lymphoid interstitial pneumonia (idiopathic LIP) and to discuss its diagnosis, treatment and prognosis. METHODS: Respiratory physicians, pathologists and radiologists together retrospectively analyzed the clinical, chest roentgenogram, computerized tomography, pathological, diagnostic and therapeutic data of 3 patients with idiopathic LIP confirmed by lung biopsy, and reviewed the relevant literatures. RESULTS: The major symptoms of the 3 cases of idiopathic LIP were progressive dyspnea and dry cough. Higher levels of gamma-globulins in serum were found in all the cases. The characteristic radiographic manifestations were bilateral diffuse nodules and cysts. The pathologic feature was diffuse interstitial inflammation with polyclonal lymphocytes infiltration, especially with plasma lymphocytes. Corticosteroids and cytotoxic agents were used and good response to therapy was observed in the cases. CONCLUSIONS: Idiopathic LIP has some characteristics on the clinical, radiological and pathological features, but the best diagnostic method depends on a clinical-radiological-pathological approach. The disease usually shows good response to combinative therapy of corticosteroids and cytotoxic agents.

[The clinicopathological features and surgical treatment of solitary fibrous tumor of the pleura].

OBJECTIVE: To investigate the clinicopathological features and surgical treatment of solitary fibrous tumor of the pleura (SFTP). METHODS: The clinical, radiological and pathological features of 11 cases of SFTP were analyzed. The detection of immunohistochemistry, surgical treatment and follow-up data were also reviewed. RESULTS: The group consisted of 6 males and 5 females, age ranging from 35 to 73 years (mean 53.7 years). Clinical findings were mainly cough, chest pain and other local symptoms. Five cases had pleural effusion. Surgical excision was performed by thoracotomy in 6 patients, by video-assisted thoracoscopic surgery (VATS) in 3 patients, and by VATS plus a small thoracotomy in 2 patients. Eight cases received tumor resection by wedge resection of the lung, and the other 3 patients by middle and lower lobe resection, lower lobe resection and chest wall tumor resection, respectively. Nine tumors were located in the visceral pleura, 1 tumor below the visceral pleura, and 1 tumor in parietal pleura. Histopathologically, SFTP consisted mainly of spindle-shaped cells which were diffusely distributed. There were abundant gross collagenous fibers and thick-walled blood vessels around tumor cells. Malignant tumors displayed high cell density, nuclear atypia and patho-karyokinesis. The tumor cells were stained with vimentin (100%, 11/11), CD(34) (100%, 11/11), CD(99) (63.6%, 7/11), and bcl-2 (63.6%, 7/11), but no expression of CD(31). Of the 11 cases, 9 were histologically diagnosed as benign SFTP, 1 as cell-abundant type of SFTP, and another as malignant SFTP. One patient died of multiple organ failure after surgery. The mean duration of hospital stay after surgery was 11 days. Follow-up visit results were available for 10 cases. The follow-up time ranged from 12 to 48 months and all patients remained well without recurrence or metastasis. CONCLUSIONS: SFTP should be considered when chest X-ray and CT showed single nodule or mass in the pleura. The diagnosis is based on examination of histopathology and immunohistochemistry. For a tumor with a diameter les than 5 cm, resection by VATS or VATS plus small thoracotomy is a good surgical procedure.

[The clinical diagnosis and analysis of pulmonary mucosa associated lymphoid tissue lymphoma].

OBJECTIVE: To improve the diagnosis of pulmonary mucosa associated lymphoid tissue (PMALT) lymphoma. METHOD: The clinical and radiographic data of 13 cases of pathology confirmed PMALT lymphoma admitted from June 1998 to June 2006 were respectively analyzed. RESULTS: There were 9 males and 4 females, with an average age of 55 years. The course of the disease was 1.5 - 108 months (average 14 months). Clinical features were nonspecific, with mild symptoms including cough, chest pain, breathlessness, hemoptysis, fever, and weight loss. Some cases were suspected in the routine physical examination. Chest radiography showed multiple lesions, commonly bilateral (7/13). The lesions were of varied manifestations, including masses (2/13), nodules (2/13), increased airspace consolidation with air bronchogram (9/13) and pleural fluid (4/13). Bronchial stenosis and inflammation (6/13) were present under bronchoscopy. CONCLUSIONS: PMALT is not common, and tends to affect middle aged and older males. The disease progresses slowly and the clinical features are nonspecific.

[Diffuse myxoid malignant fibrous histiocytoma of the pleura: a case report and review of the literature].

OBJECTIVE: To study the clinicopathologic characteristics of diffuse myxoid malignant fibrous histiocytoma (MFH) of pleura. METHODS: The clinical and pathological features of a patient with diffuse myxoid MFH of pleura from this hospital were analyzed, and the reported literature of 7 patients with MFH of pleura were reviewed. RESULTS: The patient was a 65-year-old male. The primary manifestations were cough, chest pain, breathlessness, and a great quantity of bloody pleural effusion. Chest CT scan showed diffuse masses on the visceral and parietal pleura. Exploratory thoracotomy exposed diffuse translucent gray-white masses on the surface of visceral and parietal pleura, with diameters of 1 - 8 cm. Microscopic findings showed that diffuse spindle-shaped and pleomorphic tumour cells were within the myxoid stroma. Tumor cells were positive for vimentin, CD(68), lysozyme, and negative for CK, EMA, and desmin. The patient died of obstruction of superior vena cava, and circulatory failure at 24th postoperative day. Different from cases with single or multiple MFH of pleura reported in the literature, this case of diffuse myxoid MFH had an abrupt onset, and progressed aggressively. CONCLUSION: Diffuse myxoid MFH of pleura is a very rare high-grade malignant tumor with very poor prognosis.

[Clinical analysis of 25 cases of biopsy-proven cryptogenic organizing pneumonia].

OBJECTIVE: To analyze the clinical, radiological and pathological features, diagnosis and response to therapy as well as prognosis of 25 cases of cryptogenic organizing pneumonia (COP). METHODS: Twenty-five subjects with COP confirmed by lung biopsy in Shanghai Pulmonary Hospital from January of 2000 to April of 2006 were retrospectively reviewed. Secondary reaction to infections, drugs, radiation, connective tissue diseases and various noxious agents were excluded. Their clinical-pathological characteristics, radiological features, response to treatment, relapse, survival were obtained from medical records and a follow-up patient questionnaire. RESULTS: There were 6 males and 19 females, with a mean age of 56 years (range 40 - 73 years). The presentations included cough (25/25), clear sputum (21/25), dyspnea (17/25), hemoptysis (5/25), fever and sweats (3/25), and "Velcro" crackles (18/25). Four of them were smokers, 11 had allergic reaction to some drugs, and 11 had some industrious dust inhalation. In 23 cases the specimens were obtained by video-assisted thoracoscopy and 2 cases by transbronchial lung biopsy. Bilateral lung involvement was present in 23 cases and all of them had at least two different radiological manifestations. Twenty-four cases showed a sub-pleural distribution. Bilateral patchy alveolar and ground glass involvement were found in 8 cases, airspace consolidation in 8 cases, mass in 11 cases, irregular lines in 10 cases, small nodules (<10 mm) in 4 cases. Two patients received operation. Corticosteroid therapy was administered to 23 patients. Seventeen cases were cured, but 8 of them relapsed after stopping (n = 2) and tapering (n = 6, when prednisone less than 5 - 10 mg/d) of corticosteroids within one to two years of therapy. CONCLUSIONS: COP is not very rare in China. The clinical-radiological-pathological diagnosis (CRP) is the most important diagnostic method. Corticosteroid is the first choice for COP therapy. The prognosis of COP is good if therapy is started in time, but relapse is common.

[Clinicopathologic study of cryptogenic organizing pneumonia].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of cryptogenic organizing pneumonia (COP). METHODS: The clinical, radiologic and pathologic features of 11 patients with COP confirmed by open or video-assisted thoracoscopic (VATS) lung biopsy were analyzed. Treatment information and follow-up data were also obtained. RESULTS: COP usually affected female patients over 40 years of age. Clinical presentations included cough, sputum and exertional dyspnea. High-resolution computerized tomography showed scattered speckled, patchy and trabecular shadows over both lung fields. Honeycomb changes were not found. Histologically, polypoid growths of granulation tissue were noted within respiratory bronchioles, small airways and alveolar spaces. These lesions had a patchy and peribronchiolar distribution and were uniform in appearance. The overall response rate to glucocorticoid was 81.8% (P < 0.01). The duration of follow up ranged from 6 to 134 months. Apart from one patient who developed aggravation of symptoms, the disease pursued a relatively stable clinical course. CONCLUSIONS: In general, COP responds well to glucocorticoid therapy. Open or VATS lung biopsy is important for arriving at a definitive diagnosis, especially for those cases presenting with atypical clinical and radiographic manifestations. Multiple biopsies with larger samples are preferred in order to avoid misdiagnosis.

An Intracranial Gliosis Mimicking Neoplasm: A Dilemma.

Intracranial gliosis has no typical clinical signals or imaging characteristics. Therefore, it can be easily misdiagnosed as neoplasm. Hereby, we report a unique case of gliosis that grew outward from the surface of the brain. MRI depicted its signal and enhancement pattern similar to the cerebral gray matter. The diagnosis was confirmed by pathology and immunohistochemistry. Although it was difficult to reach a diagnosis, correlating its origin, growing pattern and MR features and knowing that gliosis can present this way may help in differentiating it from other diseases.

[The value of detection of gene rearrangement of immunoglobulin heavy chain and immunohistochemistry in pulmonary mucosa-associated lymphoid tissue type lymphoma].

OBJECTIVE: To investigate the features of gene rearrangement of immunoglobulin heavy chain (IgH) and immunophenotypes of pulmonary mucosa-associated lymphoid tissue type lymphoma (MALTLoma). METHODS: The clinical and pathological data of 12 cases with pulmonary MALTLoma and follow-up information were retrospectively reviewed, and the paraffin-embedded samples were examined with immunohistochemistry staining (12 cases) and semi-nested polymerase chain reaction (PCR) for IgH and T-cell receptor gamma (TCRgamma) gene rearrangement (7 cases). RESULTS: The patients included 9 cases confirmed by open or video-assisted thoracoscopic lung biopsy and 3 cases by needle lung biopsy. Histopathologically, the tumors were composed of a spectrum of cell types that included mainly centrocyte-like cells and small lymphocytes. Lymphoepithelial lesions were identified in 12 cases, reactive colliculus lymphaticus in 11 cases, follicular colonization in 10 cases, vascular infiltration in 9 cases, and pleura involvement in 4 cases. All cases showed immunoreactivity for B-cell correlative markers. Positivity for FR2 and FR3A primers in MALTLoma were found in 6 case and 5 case respectively. The detection of TCRgamma1 and TCRgamma2 was negative in 7 cases. The combined positive rate was 100%. Chemotherapy alone was administered in 3 patients, surgery alone was performed in 8 patients, and chemotherapy after operation was carried out in 6 patients. Follow-up data were available in 11 patients. Eight of them were alive and stable, one experienced relapse and two died of the disease within 11 years and 12 years after diagnosis respectively. CONCLUSIONS: Most of the cases of pulmonary MALTLoma can be diagnosed with morphology and immunohistochemistry staining if the lesions are typical. PCR detection of IgH gene rearrangement would be helpful in differential diagnosis from benign lymphoplasia of the lung.

[Pathological diagnosis and ultrastructure features of primary pulmonary cryptococcosis: a study of 27 cases].

OBJECTIVE: To investigate diagnostic histopathology and ultrastructure features of primary pulmonary cryptococcosis (PC). METHODS: Clinical data and pathologic findings of 27 cases of PC were retrospectively reviewed, light and electron microscopic evaluations and histochemistry stain studies were performed. RESULTS: The specimens consisted of 2 fine-needle aspiration lung biopsies and 25 cases of open lung biopsies. Cryptococcosis granuloma formation was identifiable by histopathological examination in 25 of 27 cases, with gum-like lesion and fungi in the remaining 2 cases. The detection rates of cryptococcus neoformans (CN) by mucicarmine (MC), periodic acid-Schiff (PAS), alcian blue (AB) and Grocott methenamine-silver (GMS) were 87.0% (20/23), 100% (27/27), 66.7% (18/27), and 100% (23/23) respectively. Under the electron microscope, most CN had a simple structure with a few organelles. The capsule was seen in all organisms. A percentage of the organisms showed nuclei, nucleoli, mitochondria and vacuoles. The detection rate of CN by EM was 91.7% (11/12). CONCLUSIONS: The clinical manifestation and imaging of PC are nonspecific for PC. Lung biopsy is the major diagnostic modality. The detection rate by electron microscopy was quite high. Therefore, a correct diagnosis of pulmonary cyrptococcosis should rely on the combination of histopathological evaluation, histochemistry staining and/or electron microscopic examination.

[Clinicopathologic features of usual interstitial pneumonia and its differential diagnosis from idiopathic nonspecific interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic features of usual interstitial pneumonia (UIP) and its differential diagnosis from idiopathic nonspecific interstitial pneumonia (INSIP). METHODS: The clinical and pathological features of 15 UIP and 11 cases of INSIP, having received open or video-assisted thoracoscopic lung biopsies and having follow-up information were reviewed. RESULTS: UIP occurred more often in males over 50 years of age. Clinical findings included progressive shortness of breath, cough, sputum and crackles over both lung fields. High resolution computerized tomography (HRCT) showed patchy attenuation, especially over both lower lobes. Honeycombing was found in 8 cases. Histologically, UIP was characterized by scattered fibrotic foci, fibrosis (often associated with honeycombing) and pulmonary architectural destruction. It had a heterogeneous appearance, with alternating areas of normal lung, interstitial inflammation, fibrosis and honeycomb changes. The frequencies of fibroblastic foci, muscle sclerosis, honeycomb changes, diffuse fibrosis and pulmonary architectural destruction in UIP and INSIP were 100% and 27.3% (P<0.001), 80.0% and 36.4% (P<0.05), 86.7% and 27.3% (P<0.001), 100% and 54.5% (P<0.01) and 100% and 45.5% (P<0.05), respectively. The response rate to glucocorticoid was 26.7% and 72.7% (P<0.05) in UIP and INSIP respectively. CONCLUSIONS: The distinction between UIP and INSIP is difficult if based on clinical examination alone. HRCT is helpful for differential diagnosis in some difficult cases. Definite diagnosis depends mainly on open lung biopsies. Key histologic features of UIP include heterogeneous appearance with interstitial inflammation, fibroblastic foci, scar formation and honeycomb changes.

[Comparative analysis of respiratory bronchiolitis-associated interstitial lung disease and desquamative interstitial pneumonia].

OBJECTIVE: To investigate the clinicopathologic characteristics of respiratory bronchiolitis-associated interstitial lung disease (RBILD) and its relationship to desquamative interstitial pneumonia (DIP). METHODS: The clinical and pathological data of one patient with RBILD confirmed by video-assisted thoracoscopic lung biopsy were reviewed retrospectively, and compared with one patient with DIP. RESULTS: Both patients were 57 year old male, and they had a history of cigarette smoking for 24 and 30 years respectively. The clinical manifestations were cough and sputum production, breathlessness with exertion, and crackles on chest examination. Lung function test showed a mild abnormality with mixed obstructive-restrictive and restrictive pattern respectively. The chest radiograph showed scattered small nodules and patchy densities. High resolution computer tomography showed scattered interstitial infiltrates and reticular changes in the middle and lower lung fields, but patchy ground-glass attenuation was found only in DIP. The pathological examination showed the presence of clusters of pigmented macrophages within the lumens of respiratory bronchioles, alveolar ducts and peribronchiolar alveolar spaces, with patchy submucosal and peribronchiolar infiltration of lymphocytes and histiocytes. Mild peribronchiolar fibrosis was found in RBILD. Compared with RBILD, the lesions of DIP were more severe and widespread. Both the patients responded favorably to glucocorticoids. They were followed for more than three years. CONCLUSION: RBILD could be confused with DIP in clinical manifestations, but can be separated by open lung biopsy. Considering their similarities, these two lesions may be regarded as a same disease entity.

[Biologic significance of thyroid transcription factor-1 and surfactant protein expression in pulmonary sclerosing hemangioma].

OBJECTIVE: To investigate the biologic significance of thyroid transcription factor-1 (TTF-1) and surfactant protein A (SP-A) and SP-B expression in pulmonary sclerosing hemangioma (PSH). METHODS: TTF-1, SP-A, SP-B, epithelial membrane antigen (EMA), pancytokeratin (AE(1)/AE(3)), vimentin, CK7, CK5/6, calretinin, S-100, neuron specific enolase (NSE), synaptophysin (Syn), chromogranin A (CgA), CD(34), Factor VIII and smooth muscle actin (SMA) in 42 patients with PSH were examined with immunohistochemistry, while samples from 10 patients were also observed by electron microscope. RESULTS: Histopathologically, PSH mainly consisted of both surface lining cuboidal cells and pale polygonal cells. Both of them were stained with TTF-1, EMA and vimentin, whereas SP-A, SP-B, pancytokeratin and CK7 were only positive in surface lining cuboidal cells. Syn, NSE, S-100 and CgA showed scattered positivity in these cells. There was no significant difference in the expressions of TTF-1 and EMA between these two cell types (P > 0.05), whereas the difference was significant in the expression of vimentin (P < 0.01). The ultrastructural features cannot differentiate these two cells by electron microscope. CONCLUSIONS: It is suggested that PSH is derived from primitive respiratory epithelium, and both surface lining cuboidal cells and pale polygonal cells were entity cells of the tumor. Examination of different immunohistochemical markers including TTF-1, SP-A, SP-B, pancytokeratin, EMA and vimentin is helpful in the diagnosis and differential diagnosis of PSH.