Airway-centered interstitial fibrosis - an under-recognized subtype of diffuse parenchymal lung diseases.

Airway centered interstitial fibrosis (ACIF) has been recently suggesed as a rare histological pattern of interstitial lung disease of variable etiology and outcome. It is characterized by fibrosis of the respiratory bronchioles and the peribronchiolar interstitium. We describe the clinical features of 13 patients (7 female, mean age 55 years) with histologically proven ACIF in 12 cases and long-term follow up. In ten patients, exogenous agents could be detected (mould n=5, wood n=2, leather exposure n=1, occupational exposure n=2). Two patients had rheumatoid arthritis and 1 patient suffered from recurrent aspiration. In three patients no associated exposure could be detected. Eight patients were never-smokers, while five were ex- smokers. At time of diagnosis patients presented with a moderate restrictive ventilation impairment and sever reduction in diffusion capacity (VC 61%, TLC 66%, DLCOc-SB 38% pred.). All patients were started on immunosuppressive therapy with steroids which were combined with azathioprine in seven and with mycophenolate mofetil in one patient. Median time of follow up was 52 months (2-127 months). Patients with ACIF due to exogenous agents or associated with RA were stable with immunosuppressive therapy. One patient with idiopathic ACIF showed a progressive deterioration within 29 months despite immunosuppression and died while on a waiting-list for lung transplantation. In our experience ACIF is a rare finding, which is relatively frequently observed in the context of hypersensitivity pneumonitis, aspiration and rheumatoid arthritis, while idiopathic ACIF was a minority. In the majority of patients, ACIF showed a favorable long-term outcome with immunosuppressive therapy. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 218-229).

[Endobronchial Ultrasound Guided Needle Aspiration of a Lung Cyst and Eosinophilic Pneumonia]. / EBUS-Punktion einer Lungenzyste und eosinophile Pneumonie.

We report the case of a young male patient with a solitary pulmonary echinococcus cyst. The diagnosis of Cystic Echinococcosis is based on clinical findings, imaging and serology. In the setting of lung cysts the diagnosis can be difficult, particularly as the sensitivity of the serologic tests is lower compared to liver cysts. Bronchoscopic ultrasound of the cystic lesion and respectively the analysis of the cyst aspirate can lead to the diagnosis. In the present case an eosinophilic pneumonia as the result of the puncture has to be discussed.

[Diffuse Pulmonary Ossification]. / Diffuse pulmonale Ossifikation.

Diffuse pulmonary ossification (DPO) represents an uncommon condition usually associated with different underlying pulmonary and extrapulmonary diseases. In this work, we discuss eleven patients of our clinic with the diagnosis of a diffuse pulmonary ossification. We focus on histological changes in the surrounding lung tissue. Clinical and radiological findings were analysed. The aim of the study is to collect data for a better understanding of this condition, especially in association with interstitial lung disease.Three patients with interstitial lung disease had histological findings of UIP. The follow-up data of these patients showed a benign course of the disease.The analysis of the clinical data yielded a very heterogenous group. Regarding these fact we assume, that DPO is not an own entity, but a pathological epiphenomenon in the context of different conditions, possibly with pathogenetic overlap.

[Diffuse pulmonary meningotheliomatosis]. / Diffuse pulmonale Meningotheliomatose.

In two patients with bilateral micronodular pulmonary changes a diffuse pulmonary meningotheliomatosis was found. A 73-year-old woman presented with bilateral disseminated miliary pulmonary nodules as a radiological incidental finding. The surgical lung biopsy showed multiple tiny nodular proliferations meningothelial-like cells, corresponding "minute pulmonary meningothelial-like nodules", MPMN. A 60-year-old lady with similar radiological findings showed also proliferations of meningothelial-like cells in a transbronchial cryo-biopsy. These lesions are well known to pathologists as curious isolated incidental findings on histological examination of lung specimens. The here described diffuse form of these changes is very rare; its knowledge is important for the differential diagnosis with neoplastic proliferations and other diffuse parenchymal diseases of the lung. This rare diagnosis is made on histological grounds and is also possible in transbronchial biopsies when careful correlation with clinical and radiological data, knowledge of the entity and adequate specimens are provided.

[Molecular pathological diagnosis in cytopathology of non-small-cell lung cancer. Standardization of specimen processing]. / Molekularpathologische Diagnostik in der Zytopathologie des nichtkleinzelligen Lungenkarzinoms. Standardisierung der Materialprozessierung.

BACKGROUND: Personalized medicine is becoming standard for the treatment of non-small-cell lung cancer. For example, patients with activating EGFR mutations or EML4-ALK translocations largely benefit from targeted therapies with tyrosine kinase inhibitors with better response rates and progression-free survival compared to standard chemotherapy regimens. However, the application of the respective molecular biomarker analyses requires great expertise in the handling of different cell and tissue specimens. A major challenge for reliable analyses is the usually low amount of tumor material. There are currently relatively few standardized and evidence-based guidelines for the processing and analysis of respective specimens as well as for interpretation of the test results. MATERIALS AND METHODS: To establish a basis for standardized predictive cytopathological analyses, different material processing approaches and molecular pathological tests are discussed, and novel concepts and strategies are lined out in order to improve the quality and reliability of the respective diagnostic procedures. RESULTS AND DISCUSSION: Predictive analyses of cytological specimens can be reliably performed using smears, cytospins or cell blocks; there is no need for histological specimens. The diagnostic work-up of cytological probes should be performed as carefully as possible in order to save further tumor material for subsequent predictive analyses. With standardized and reliable procedures at hand cytopathology is an important contribution to the multidisciplinary, complex care, and treatment of lung cancer patients.

[Diagnostic and predictive analyses of cytological specimens of non-small cell lung cancer: strategies and challenges]. / Diagnose und prädiktive Analysen an zytologischen und bioptischen Tumorproben nicht-kleinzelliger Lungenkarzinome: Aktuelle Strategien und Herausforderungen.

Personalised medicine is becoming the standard care for advanced non-small cell lung cancer. Tumour-specific therapies based on biomarker analyses, e. g., EGFR mutations or translocations of the ALK gene locus, result in a superior patient outcome compared to unselected therapy approaches. However, predictive molecular analyses can be challenging and require significant experience with cell- and tissue-based diagnostic methods. The major challenge relates to the sometimes low amount of available tumour material for both diagnostic and predictive analyses. As yet, there are no standardised or evidence-based recommendations concerning biopsies, specimen processing, and analyses. Respective guidelines require combined interdisciplinary actions to consider both clinical and pathological aspects. In order to establish a basis for high quality procedures, different approaches, methods, and protocols were interdisciplinary discussed with an emphasis on cytological specimens. Detailed evaluation of the parameters and consented recommendations might contribute to optimised strategies in the interdisciplinary, more and more complex care of non-small cell lung cancer patients.

[Epithelial-myoepithelial carcinoma of the trachea. Case report and review of the literature]. / Epithelial-myoepitheliales Karzinom der Trachea. Fallbericht und Literaturübersicht.

The tracheobronchial glands are considered to be counterparts of the minor salivary glands in the respiratory tract and can develop similar tumors (tumors of salivary gland type). Within this group of neoplasia epithelial-myoepithelial carcinoma of the respiratory tract is very rare and the diagnosis is often difficult. The first case of this tumor entity in the trachea is reported and a review of the literature on these tumors is presented. The exact histological classification as well as the localization and the endoscopic findings of these lesions are crucial for therapeutic decision-making.

[Giant hamartoma of the lung]. / Riesiges Hamartom der Lunge.

Hamartomas are the most common benign tumors of the lungs and usually present as solitary intraparenchymal lesions a few centimeters in diameter which are detected radiologically as an incidental finding. This article reports on a case of a giant pulmonary hamartochondroma 29 cm in diameter, which impressed preoperatively and intraoperatively as an extrapulmonary neoplasm. The detection of smaller mesenchymal neoplastic lesions in the lungs and pleura is a further special feature of this case.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

[Biopsy diagnosis of papillary adenoma of the lung by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA)]. / Bioptische Diagnose eines papillären Adenoms der Lunge mittels Ultraschall-gesteuerter transbronchialer Nadelaspiration (EBUS-TBNA).

The papillary adenoma of the lung is a rare benign neoplasia with intraparenchymal localisation and is thus, in general, difficult to access for biopsy diagnosis. Due to the rarity of this lesion, the intra-operative histological diagnosis by frozen section may be problematic. We report on a 75-year-old male patient with a lung nodule, biopsied by means of bronchoscopy with TBNA. The tissue obtained was processed histologically as a cell block and examined microscopically. The diagnosis of a papillary adenoma was made. Our case is the first report on the diagnosis of a papillary adenoma of the lung by TBNA biopsy. For our patient with impaired lung function the diagnostic procedure described here represented a less invasive alternative to the diagnostic evaluation by surgery with intraoperative frozen section examination. This case shows that the TBNA biopsy combined with processing of the tissue as a cell block may represent a contribution to the appropriate management of the patients and serve as an aid for therapy planning.

Two malignant tumours in the anterior mediastinum positive for CD5.

To our knowledge, the simultaneous involvement of the anterior mediastinum by a thymic carcinoma and a B-cell chronic lymphocytic leukaemia has not been reported previously. The authors describe the case of a 62-year-old man, suffering from severe bronchitis. Chest x-ray and CT scan showed a mediastinal tumour, resected short-time after diagnosis. First, standard based histological examination revealed a thymic carcinoma admixed by a dense lymphatic infiltrate. Additional immunohistochemical staining for CD5-labelled epithelial thymic carcinoma cells as well as neoplastic B cells and led in combination with blood tests to confirm the diagnosis of the composite occurrence of a thymic carcinoma and a B-cell chronic lymphocytic leukaemia.

[Granulomatous bronchiolitis due to aspiration of lycopodium spores by fire-breathing]. / Granulomatöse Bronchiolitis nach Aspiration von Lycopodium-Sporen bei einem Feuerspucker.

BACKGROUND: Lung disease due to aspiration is often unsuspected and represents a diagnostic challenge. CASE REPORT: We report on a 23-year-old male patient with cough, fever and infiltrates on the chest radiograph. The lung biopsy showed granulomatous changes consistent with tuberculosis. The surgical lung biopsy revealed aspiration bronchiolitis with necrosis, granulomatous changes and particulate foreign material. RESULTS: The aspirated matter could be identified only after repeated interrogation specifically directed to the matter. The patient had aspirated Lycopodium spores in the course of occasional fire-breathing. CONCLUSIONS: This is the first report on pulmonary disease due to aspiration of Lycopodium spores in the course of fire-breathing. It shows that the anamnesis is as crucial as histology for the definitive diagnosis of aspiration disease.

[Thymic cyst with initial malignant transformation]. / Thymuszyste mit beginnender maligner Entartung.

We present the case of a 38-year-old woman with a thymus cyst with an incidental tiny adenocarcinoma. Adenocarcinomas and adenosquamous carcinomas of the thymus or in thymus cysts have seldom been reported. These cases were overt invasive carcinomas. Our case is the first report on an incipient adenocarcinoma in a thymus cyst. It demonstrates the importance of thorough histological examination of cystic changes in the thymus, not only for the diagnostic classification of the lesion but also to ensure that a possible malignant change is not overlooked.

[The ovarian hyperstimulation syndrome -- a rare differential diagnosis of a unilateral pleural effusion]. / Das ovarielle Hyperstimulationssyndrom -- eine seltene Differenzialdiagnose des einseitigen Pleuraergusses.

This case presentation describes a 29 year-old female who developed a severe ovarian hyperstimulation syndrome (OHSS) with ascites and a right-sided pleural effusion following in-vitro-fertilisation. A total of 4,2 l of pleural fluid was removed during 3 thoracocenteses. The symptoms as well as the fluid production ceased after 2 weeks. The OHSS is altogether a rare, but potentially life-threatening complication of in-vitro-fertilisation. Due to the well-characterized clinical setting in which the syndrome appears, there are only few differential diagnoses to consider. OHSS is likely to originate from altered capillary permeability, but its pathogenesis is not yet fully understood. Clinical symptoms usually resolve within 2 weeks of supportive therapy. In case of persistency, however, especially pulmonary embolism and infectious causes of pleural fluid production have to be excluded.

[Endobronchial lipoma: successful therapy by bronchoscopical laser resection vs. surgery]. / Endobronchiales Lipom: erfolgreiche Therapie mittels bronchoskopischer Laserresektion versus Chirurgie.

BACKGROUND: Endobronchial lipoma is a very rare benign lung tumor. Therapeutic alternatives are the interventional bronchoscopic laser resection or surgical treatment. METHODS: From 1996 to 2002 we diagnosed 16 patients with endobronchial lipoma in our institution. We examined the clinical data of the patients and their influence on the individual patient treatment. RESULTS: 14 (88 %) out of the 16 patients (60 +/- 14 y.) were male. Clinical symptoms were cough (81 %), dyspnea (75 %), pulmonary infiltration (63 %) and fever (31 %). In the right lung 11 lipomas (69 %) were located, in the left lung 5 lipomas (31 %). The distribution to main bronchus, upper lobe, middle lobe and lower lobe bronchus were 2 (12.5 %), 6 (37.5 %), 2 (12.5 %) und 6 (37.5 %). 14 (88 %) lipomas were found in the central airways, 2 were located in the periphery of the lung. All lipomas in the central airways were successfully treated by bronchoscopic laser therapy with a mean of 1.1 +/- 0.3 laser sessions. One patient died of concomitant bronchial carcinoma before therapy. Surgical treatment was only necessary in a very peripherally located huge lipoma and a lipoma with extensive parenchym destruction. CONCLUSIONS: Bronchoscopic laser resection should be considered as first line therapy in cases of endobronchial lipoma. It is safe, successful, rapid and less expensive compared to surgical resection. Surgery should only be indicated in patients with lipomas with very peripherally localisation or parenchym destruction, extrabronchial growth, suspected malignancy or technical problems at bronchoscopic resection.

[Pulmonary infiltrates with blood eosinophilia in a 62-year-old patient]. / Pulmonale Infiltrate mit Bluteosinophilie bei einer 62-jährigen Patientin.

A 62-year-old woman was admitted because of chronic cough and bilateral infiltrates on chest roentgenogram. Additional history revealed that the patient had been taken diclofenac emulgel during the previous 10 years for arthrosis. Diagnostic bronchoscopy showed eosinophilic alveolitis. After ruling out infectious, parasitic or systemic diseases drug-induced eosinophilic pneumonia was diagnosed due to topical diclofenac therapy and subsequent percutaneous drug absorption. No previous case of eosinophilic pneumonia to topical diclofenac was discovered in our review of the literature. The diclofenac therapy was discontinued. Oral corticosteroid therapy cleared bilateral infiltrates on CT scan within seven days. Drug reactions are the most common cause of pulmonary infiltrates with blood eosinophilia and/or eosinophilic alveolitis and should be considered as a differential diagnosis.

[Micronodular pneumocyte hyperplasia in pulmonary lymphangioleiomyomatosis and tuberous sclerosis]. / Mikronoduläre Pneumozytenhyperplasie bei pulmonaler Lymphangioleiomyomatose und tuberöser Sklerose.

An open lung biopsy was performed in a 28-year-old woman with tuberous sclerosis and with spontaneous pneumothorax and interstitial changes in the chest X-ray. Microscopically a micronodular pneumocyte hyperplasia in addition to a lymphangioleiomyomatosis was found. The micronodular pneumocyte hyperplasia is considered to be a very rare lesion. Only 27 well documented such cases have been recorded so far, 24 in women and 3 in men. The age of the patients ranged between 20 and 57 years, with an average of 36 years. The micronodular pneumocyte hyperplasia occurs mainly in patients with tuberous sclerosis (20 of 27 cases) and it is often combined with a lymphangioleiomyomatosis (19 cases). In the differential diagnosis the atypical adenomatous hyperplasia is to be considered in the first place. In contrast to it, the proliferating cells of the micronodular pneumocyte hyperplasia show no atypia. The differentiation from a papillary adenoma can be difficult in small biopsies.

[Choristoma of the diaphragm. Case report of a rare tumor and approach through lateral thoracotomy]. / Choristom des Zwerchfells - Kasuistik eines seltenen Tumors und Versorgung desselben durch laterale Thorakotomie -

Tumors of the diaphragm are rare and caused by there special localisation difficult to diagnose. We describe the case of a 31 year old man with a choristoma of the left diaphragmal crux where the localisation and genesis could only be cleared through lateral thoracotomy. Nor the CT guided puncture or the laparoscopy-although sufficient samples for the pathology could be gained-allowed the right diagnose. The importance of good diagnostic approach to select the right operative procedure-in this case the anterolateral thoracotomy-is described.

Inhalation of aerosolized vitamin a: reversibility of metaplasia and dysplasia of human respiratory epithelia -- a prospective pilot study.

The objective of this preliminary uncontrolled study was twofold: First, to assess the feasibility of retinyl palmitate inhalation and second, to analyze the changes of metaplastic lesions of the respiratory epithelium (metaplasia or dysplasia) following retinyl palmitate inhalation. The response to a daily dose of 18.000 I.U. retinyl palmitate by inhalation over a period of 3 month was assessed in 11 subjects (9 smokers, 2 ex-smokers). Using white-light bronchoscopy combined with autofluorescence bronchoscopy, bronchial biopsies were taken before and after a 3 month-period. The biopsy samples were evaluated blind by a referee lung pathologist. The overall response rate (remission or partial remission) was 56% (95% CI 0.30 0.79; p<0.05). These data suggest that inhalation of retinyl esters could be a promising therapeutical approach for chemoprevention of lung cancer. Vitamin A; chemoprevention; lung cancer; squamous metaplasia; dysplasia; retinoids

Significance of lymphangiosis carcinomatosa at the bronchial resection margin in patients with non-small cell lung cancer.

BACKGROUND: Treatment options for patients with microscopic residual disease at the bronchial margin (R1-resection) after resection for non-small cell lung cancer include observation, radiotherapy, reoperation, or even systemic therapy. The present study was performed to identify a parameter that would estimate the prognosis of these patients more precisely to permit a well-founded treatment recommendation for the individual patient. METHODS: A total of 1,162 patients with resected non-small cell lung cancer were analyzed in this retrospective study. Fifty-four patients (4.6%) had R1-resections at the bronchial margin. Type of residual disease (mucosal, extramucosal, or involvement of the entire bronchial wall) and occurrence of tumor cells in the lymphatic vessels (lymphangiosis carcinomatosa) were recorded as distinct parameters and analyzed by univariate and multivariate analyses (Log rank test; Cox regression model). RESULTS: Lymphangiosis carcinomatosa at the bronchial margin was detected in 22 patients (40.7%) and was associated with a significantly shortened survival (median survival with lymphangiosis carcinomatosa, 13.3 months; without lymphangiosis carcinomatosa, 20.1 months; p = 0.026). Early stage patients (stage I-II) without lymphangiosis carcinomatosa showed a median survival of 49 months. Multivariate analysis revealed that lymphangiosis carcinomatosa at the resection margin is an independent prognostic parameter (p = 0.038). Even after postoperative radiotherapy the prognosis was still poor if a lymphangiosis carcinomatosa was detected (median survival, 17.1 months). All other parameters (T-stage, N-stage, tumor histology, type of bronchial wall involvement) were not of prognostic significance in R1-resected patients. CONCLUSIONS: Lymphangiosis carcinomatosa at the bronchial resection margin predicts a poor prognosis in patients with non-small cell lung cancer. It is more than questionable whether these patients would benefit from local treatment options like radiotherapy.