초록 ▼

개발 목적 및 필요성
석면피해구제제도 시행 후 석면관련질환의 표준화된 진단기준이 없어서 석면피해판정에 어려움을 겪게 되었다. 한국인에게 발생하는 석면관련질환의 진단기준이 표준화되면 국내의료기관에서 이 기준에 의하여 진단할 수 있으므로 정확한 진단을 기초로 한 진단자료로 일관성 있는 석면피해판정과 보상 등, 석면환경개선 정책입안에 도움을 줄 수 있다. 이에 석면관련질환의 표준화된 진단기준 지침서를 개발하고자 본 연구를 수행하였다.

연구개발 결과
악성중피종, 석면폐증, 석면관련 폐암 및 흉막반/미만성 흉막비후 등

개발 목적 및 필요성
석면피해구제제도 시행 후 석면관련질환의 표준화된 진단기준이 없어서 석면피해판정에 어려움을 겪게 되었다. 한국인에게 발생하는 석면관련질환의 진단기준이 표준화되면 국내의료기관에서 이 기준에 의하여 진단할 수 있으므로 정확한 진단을 기초로 한 진단자료로 일관성 있는 석면피해판정과 보상 등, 석면환경개선 정책입안에 도움을 줄 수 있다. 이에 석면관련질환의 표준화된 진단기준 지침서를 개발하고자 본 연구를 수행하였다.

연구개발 결과
악성중피종, 석면폐증, 석면관련 폐암 및 흉막반/미만성 흉막비후 등 석면관련질환의 표준화된 진단기준 지침서 작성을 위하여 다음과 같은 과제를 수행하였다.
1. 전국의료기관에서 진단된 악성중피종, 석면폐증, 석면노출에 의한 폐암과 흉막반/미만성 흉막비후 검체의 데이터 구축
2. 악성중피종의 진단기준 표준화
1) 악성중피종의 영상의학 진단기준
2) 악성중피종의 조직병리학 진단기준
3) 악성중피종의 세포병리학 진단기준
4) 악성중피종의 면역조직화학 진단기준
5) 양성중피증식과 악성중피종의 감별 진단기준
6) 악성중피종의 전자현미경 진단기준
7) 악성중피종의 분자병리학 진단
8) 악성중피종 병리 진단보고서 서식 개발
3. 석면폐증의 진단기준 표준화
1) 석면폐증의 영상의학 진단기준
2) 석면폐증의 임상 진단기준
3) 석면폐증의 역학 진단기준
4) 석면폐증의 병리학 진단기준
4. 석면관련 폐암의 진단기준 표준화
1) 석면관련 폐암의 영상의학 진단기준
2) 석면관련 폐암의 역학 진단기준
3) 석면관련 폐암의 병리학 진단기준
5. 흉막반/미만성 흉막비후의 진단기준 표준화
1) 흉막반/미만성 흉막비후의 영상의학 진단기준
2) 흉막반/미만성 흉막비후의 역학 진단기준

성능사양 및 기술개발 수준
아시아·태평양 지역의 석면피해 개선정책이 필요한 국가와 의료기관에서 석면관련질환의 표준화된 진단기준 지침서로 활용 가능한 수준이다.

활용계획
석면관련질환의 표준화된 진단기준 지침서가 전국의료기관에 배포되어 석면관련질환이 신속하고 정확하게 진단되고 판정이 가능해져서, 석면으로 인한 건강피해자 및 유족에게 석면피해구제제도를 통해 신속하고 공정한 구제급여 기회를 제공할 수 있다.

Abstract ▼

Ⅳ. Results
1. Nationwide data enrollment and administration of ARDs in Korea were based on the cases collected through Korea MM surveillance system (KMMS) and certified in Judgment Committee of asbestos damage relief system operating by Korea Environment Corporation (KEC).
1) For the diagnosti

Ⅳ. Results
1. Nationwide data enrollment and administration of ARDs in Korea were based on the cases collected through Korea MM surveillance system (KMMS) and certified in Judgment Committee of asbestos damage relief system operating by Korea Environment Corporation (KEC).
1) For the diagnostic guidelines of MM
We analysed and made the virtual images of 212 clinically and histologically confirmed cases of MM through the KMMS. Among these we made the tissue microarray (TMA) with excision or surgically resected samples for the immunohistochemical and molecular guidelines in 90 cases of MM, 33 cases of lung adenocarcinoma, and 35 case of benign mesothelial hyperplasia. The cytologic features in effusion of 25 pleural and 7 peritoneal MM patients were compared for the cytopathologic diagnostic guideline of MM. Paraffin embedded tissue blocks of MM (20 cases), metastatic adenocarcinoma (10 cases), and control (5 cases) were used for the EM diagnostic guideline. For the radiologic guideline of MM, 134 pleural MM and 50 metastatic pleural disease cases from 1997 to 2012 were reviewed.
2) For the diagnostic guidelines of asbestosis
We reviewed and analysed the radiologic findings of 200 cases, the epidemiologic findings of 561 cases and the clinical findings of 420 cases of asbestosis compensated by asbestos damage relief system from January, 2011 to May, 2013. The radiologic findings were compared with 11 cases of IPF enrolled from nationwide hospitals.
3) For the diagnostic guidelines of asbestos-related lung cancer
We reviewed the radiologic, epidemiologic, and pathologic features of ARLC with the data analysis of 57 patients during the last three years (2011-2013) based on the data of asbestos damage relief system supported by KECO.
4) For the diagnostic guidelines of pleural plaque and DPT
We reviewed the radiologic and epidemiologic features of pleural plaques with the data analysis of 279 asbestos-exposed subjects for radiologic guideline and 302 subjects for epidemiologic guideline who had pleural plaques during the last three years (2011-2013) based on the data of asbestos damage relief system supported by KECO.

2. Diagnostic guidelines of malignant mesothelioma
1) Histopathologic diagnostic guideline of MM
The 212 clinically and histologically confirmed cases of MM through the KMMS revealed that 67% of total cases were composed of biopsies. We applied existing guidelines for pathologic diagnosis of MM to each biopsy and excision case according to their number, and make suggestions for new pathologic guideline adjusted to specimen types.
Histologic diagnosis for specimens of potential MM should follow four histologic diagnostic algorithm of MM according to specimen type. Even though following the above algorithm, 5~10% of 1-2 piece biopsies are concluded as being inadequate for proper diagnosis and need rebiopsy. A biopsy of more than 3 pieces or excision is recommended for diagnosis of MM.
2) Cytopathologic diagnostic guideline of MM
In the cytopathologic diagnosis of MM, differential diagnosis with inflammation-associated reactive mesothelial proliferation and metastatic adenocarcinoma is often difficult. If we are familiar with key cytopathologic findings of rare MM and careful about differential diagnosis points from confusing conditions, the diagnosis of MM can be easy. However, whenever MM is suspicious from cytologic samples, histopathologic confirmative process is mandatory. Otherwise, evaluation of clinical history such as previous asbestos exposure and radiologic correlation may be helpful. Cell block and/or liquid-based cytology samples are very useful for application of immunocytochemical staining or molecular marker studies which can enhance the diagnostic efficacy of MM.
3) Immunohistochemical diagnostic guideline of MM
The immunohistochemical stainings are very useful for differential diagnosis between malignant mesothelioma and metastatic carcinoma. We recommend the use of panels composed of at least 3 positive mesothelial markers and 2 positive carcinoma markers. To distinguish malignant mesothelioma from metastatic pulmonary carcinoma, Calretinin, WT1, and D2-40 are the best positive mesothelioma markers; and MOC-31 (or Ber-EP4) and TTF-1 (or Napsin A) are the best carcinoma markers.
The immunohistochemical stainings have a limited utility for differential diagnosis between malignant mesothelioma and benign mesothelial proliferation. We recommend the use of at least 2 antibodies among EMA,Desmin, p53, IMP3, and GLUT-1. IMP3 and EMA are most helpful markers.
4) Guideline for differential diagnosis between benign mesothelial hyperplasia andMM
The Histologic findings are the most important in differential diagnosis between reactive mesothelial hyperplasia and epithelioid mesothelioma. Immunohistochemical stains are only used as ancillary tools. At least two antibodies should be used, and positivity of IMP3 and EMA are helpful in diagnosis of epitheliod malignant mesothelioma
Differentiating fibrous pleurisy from desmoplastic variant of malignant mesothelioma is very difficult. Excisional biopsy rather than needle biopsy is often needed. This can be helped by an array of infiltrating cells observed after cytokeratin-staining.
5) Electron microscopic diagnostic guideline of MM
TEM and SEM examinations can be applicable to the differential diagnosis between EMM and metastatic ADC in cases with equivocal results of immunohistochemistry.
SEM examination is very useful for diagnosis of EMM in cases with only remaining paraffin embedded small tissue block.
On TEM and SEM examination using paraffin embedded tissues as well as formalin fixed tissue or cytologic samples, the cut-off value of LDR is 5 in the differential diagnosis between EMM and metastatic ADC.
6) Molecular pathologic diagnosis of MM
FISH assessment of homozygous 9p21 deletion could be a useful diagnostic marker in diagnosing MM, and a combination of p16 immunohistochemistry showed better results. It is not effective in differential diagnosis of mesothelial proliferation from MM, but very effective in differential diagnosis of adenocarcinoma from MM.
7) Radiologic pathologic diagnosis of MM
Although CT remains the primary imaging modality to evaluate pleural MM,differentiation of pleural MM from metastatic pleural disease (MPD) is difficult because of similar CT features. Combination of characteristic CT features of pleural MM and MPD can be helpful for differential diagnosis of pleural MM from MPD.
An unexplainable pleural effusion in thoracic CT can be the first sign of pleural MM. Therefore, radiologists should review the CT images carefully to find pleural plaques suggesting history of asbestos exposure.
If pleural MM is suspected on imaging study, pathological confirmation is recommended for definite diagnosis. Clinical information including history of asbestos exposure is also needed.
8) Report form development of MM according to samples
The pathologic diagnosis of MM is necessary for biopsy and resection tissue,as well as cytology specimens. For histologic diagnosis, we suggest the reporting form including the AJCC Cancer Staging Manual. For cytologic diagnosis, there is no standardized form. So we may recommend the reporting form based on the Bethesda system category. It will be helpful for patient diagnosis and treatment using this standardized reporting form.

3. Diagnostic guidelines of asbestosis
1) Radiologic diagnostic guideline of asbestosis
Although differentiation of asbestosis and idiopathic pulmonary fibrosis (IPF) is difficult because of similar CT features, the combination of several characteristic CT features of asbestosis (parenchymal band, subpleural dotlike or branching densities, plaque, parenchymal change adjacent plaque [parenchymal bands, round atelectasis etc.]) can be helpful for differential diagnosis of asbestosis and IPF.
The possibility of asbestosis should be considered when the patient has history of asbestos exposure with pulmonary fibrosis shown in the chest CT image. Therefore, radiologists should review the CT images carefully to find pleural plaque suggesting asbestos exposure.
Pathological confirmation or diagnosis is difficult when asbestosis is suspected on chest CT imaging. Therefore clinical history including history of asbestos exposure is required.
2) Clinical diagnostic guideline of asbestosis
Since CT extent reflects the restrictive lung disease occurring in environmental asbestosis patients better than CT fibrosis score, CT extent should be used more seriously as an index for pulmonary dysfunction in environmental asbestosis patients.
Since there is a significant correlation between the degree of pulmonary function disability and CT extent, CT extent may be used to determine degree of disability. However, due to the small number of more than moderate disability, advanced disability and moderate disability should be evaluated as the same degree.
There was no significant correlation between the degree of exposure to environmental asbestos and pulmonary dysfunction. Additional collection of resources and analysis on the factors that may affect pulmonary function other than smoking, including pollution and pulmonary infection, are necessary.
Pulmonary function was observed significantly lower in the group of less severe environmental history and occupational history. In the group of more occupational asbestos exposure, it showed a high ratio of severe pulmonary disability. This indicates that split evaluation of occupational asbestos exposure and environmental asbestos exposure is necessary.
Evaluating based on the current criteria of pulmonary function disability in asbestosis shows very few cases of advanced degree of disability in case of environmental exposure. Therefore, the standard for advanced degree of disability needs to be relaxed.
3) Epidemiologic diagnostic guideline of asbestosis
Occupational exposure to asbestos is the largest contributing factor in diagnosing asbestosis. Therefore, it is necessary to provide the objective and standardized exposure assessments for asbestosis such as occupational and environmental exposure matrix.
HRCT as a radiological tool might enable us to detect early stage asbestosis due to environmental asbestos exposure. Therefore, it is difficult to compare with data from other countries which use chest x-ray as a diagnosing tool.Despite this limitation, our results suggest a high level of exposure to asbestos among residents near asbestos mines.
Unlike MM, asbestosis is related to a higher level of asbestos exposure.Therefore, the usage of familial asbestos exposure is a limited contributing factor in diagnosing asbestosis, except a cottage industry for asbestos related products.
Smoking history correlates with specific radiologic features for obstructive lung diseases by chest CT. Therefore, it should be considered when evaluating the parameters of lung function (spirometry) not diagnosing asbestos.
According to specific features of each occupational and environmental exposure to asbestos, it is necessary to evaluate them separately. Occupational exposure to asbestos is the most important factor for diagnosing asbestosis. In addition to occupational exposure to asbestos, it is useful to evaluate the combined exposure to occupational and environmental asbestos by means of exposure matrix (both occupational & environmental exposures).
Individual respiratory symptoms and previous medical history would not relate with prevalence of asbestosis. Therefore, those individual symptoms and medical history are not recommended in evaluating relatedness of asbestos exposure under the Act for Asbestos Health Damage Relief System.
4) Pathologic diagnostic guideline of asbestosis
Pathologically, asbestosis shows pattern of IPF/UIP, but less inflammatory infiltrate and more homogeneous, hyalinized and collagenous interstitial fibrosis in comparison to IPF/UIP.
In the early stage of asbestosis, the fibrosis begins in subpleural and peribronchiolar portions and extends slowly to the lung parenchyma.
In the advanced stage, diffuse interstitial fibrotic scarring with honeycombing can be observed.
Asbestos bodies are present in the alveoli or fibrotic interstitium on H&E and iron stain. Detecting rate of asbestos bodies are more than 2 in 100% of cases and more than 5 in 95% of cases per 1 cm2 of lung tissue.
Differential diagnosis of asbestosis includes IPF/UIP, smoking related interstitial fibrosis and non-specific interstitial pneumonia/fibrosis.

4. Diagnostic guidelines of asbestos-related lung cancer
1) Radiologic diagnostic guideline of asbestos-related lung cancer
Wide range of radiologic findings of asbestosis and pleural plaque was detected in the patients with asbestos-related lung cancer.
Irrespective of severity and extent, the presence of asbestosis or pleural plaques on thoracic CT could be a marker of asbestos exposure in patient with lung cancer.
In the patient with lung cancer and asbestos exposure, thoracic CT should be carefully evaluated to find asbestosis and pleural plaques for the diagnosis of asbestos-related lung cancer.
2) Epidemiologic diagnostic guideline of asbestos-related lung cancer
3) Pathologic diagnostic guideline of asbestos-related lung cancer
Asbestos-related lung cancer has to be the primary pulmonary carcinoma arising in bronchial or bronchiolar mucosal epithelial cells or pneumocytes such as squamous cell carcinoma, adenocarcinoma, small cell carcinoma, large cell carcinoma, etc.
If the asbestos body or asbestos fiber can be detected in the BAL fluid or lung tissue adjacent to lung cancer, it can be the most important evidence to support the asbestos-related lung cancer. However, this is not included in this study.

5. Diagnostic guidelines of asbestos-related plural plaque and diffuse pleural thickening
1) Radiologic diagnostic guideline of asbestos-related pleural plaque and DPT
(1) Radiologic diagnostic guideline of asbestos-related pleural plaque
Pleural plaque is the most common form of pleuropulmonary abnormality in asbestos-exposed individuals and an indicator of asbestos exposure. Pleural plaques are typically bilateral multiple localized pleural thickenings sparing the costophrenic angles, but may present as a single or unilateral lesions. Pleural plaques are variable in size and width, and calcification. Width and calcification are related to duration from first exposure, and increase on a long-term follow-up. Size is related to exposure amount.
The most common site of pleural plaques is chest wall with a lower dorsal predominance. However, ventral side (non-dependent area) plaques show upper predominance. A diaphragmatic pleural plaques involves the central tendon with right-side predominance, and is virtually pathognomonic of prior asbestos exposure. Other sites of pleural plaques include the mediastinal pleura, fissures, and pericardium. Differential diagnosis includes tuberculous pleural thickening or calcification. Pleural thickening or calcification due to tuberculosis usually occurs in unilateral hemithorax and in dependent area(inferior-posterior chest wall) with costophrenic angle bluntting, and infrequently involves the diaphragm or non-dependent area chest wall.However, in cases mimicking pleural thickening or calcification due to tuberculosis and not being pathologically confirmed, a localized pleural thickening without lung parenchymal tuberculosis in individuals with definite asbestos exposure may be considered as an asbestos pleural plaque.
Normal structures including the innermost intercostal muscle groups and intercostal vessels may simulate pleural plaques. Transversus thoracis and subcostalis muscles are usually bilateral and symmetric and observed in their normal anatomic locations. Intercostal vessels are embedded in extrapleural fat layer posterior to the interface between the lung and parietal pleura.
(2) Radiologic diagnostic guideline of asbestos-related DPT
DPT due to asbestos exposure is infrequent compared to pleural plaque,but may cause restrictive pulmonary impairment.
DPT is an extensive pleural thickening with obliteration of the costophrenic angle.
CT cannot differentiate asbestos-related DPT from pleural thickenings caused by other diseases. Therefore, a DPT, which is not pathologically confirmed, may be considered as an asbestos-related DPT in the presence of pleural plaques, or in the presence of asbestosis, or in individuals with a definite history of asbestos exposure, regardless of the presence of pulmonary tuberculosis or other pulmonary infection,
2) Epidemiologic diagnostic guideline of asbestos-related pleural plaque and DPT
The presence of pleural calcification is related with the higher occupational & environmental exposure and the lag time from asbestos exposure to diagnosis.
The associated factors for plaque length includes the higher occupational exposure and the long distance from source. However, it is not consistent with previous studies, suggesting its relationship with mixed environmental and occupational exposures in Korea.