R4 임효석

Introduction Bronchioloalveolar carcinoma (BAC) : A subtype of pulmonary adenocarcinoma that is distinguished by - its peripheral location - well-differentiated cytology - growth along intact alveolar septa (the so-called "lepidic" growth pattern) - tendency for both aerogenous and lymphatic spread

Epidemiology and Risk factors Incidence Bronchioloalveolar Carcinoma

Risk factors 1. Smoking - Patients with BAC are three to four times more likely to have ever smoked than age-matched controls, and the risk is increased with heavier and more prolonged smoking. However, approximately one-third of cases of BAC occur in individuals who have never smoked. - Another one-third are former or intermittent smokers. 2. Other postulated etiologic factors of BAC - Scarring - Occupational exposure (sugarcane farmers, petroleum manufacturers, and workers in the construction, shipping, wood, and paper mill industries) - Viral infection : jaagsiekte sheep retrovirus (JSRV)

Pathology Pathologic features of Bronchioloalveolar carcinoma (BAC) : A subtype of pulmonary adenocarcinoma that is distinguished by - its peripheral location - well-differentiated cytology - growth along intact alveolar septa (the so-called "lepidic" growth pattern) - tendency for both aerogenous and lymphatic spread WHO lung tumor classification of Adenocarcinoma and BAC : Pure BAC subtype Mixed adenocarcinoma with a BAC component

Subtypes of BAC 1. Mucinous 2. Nonmucinous 3. Mixed mucinous and nonmucinous (or indeterminated form) - Mucinous form : associated with lobar consolidation : derived from respiratory goblet cells. constituted 20 to 25% of BACs. tend to spread and form satellite tumors or pneumonic consolidation  worse prognosis - Nonmucinous form : associated with solitary lesion : show ultrastructural and immunophenotypic features of either Clara cells or type Ⅱ pneumocytes. constituted 60 to 65% of BACs. usually solitary nodules and have very good prognosis

Clinical presentation 1. Solitary peripheral nodule - localized disease is more common in patients with BAC compared to those with other types of NSCLC. (38%) - better prognosis - Many small peripheral lesions due to BAC  ground glass appearance on chest CT : improved prognosis  pure or minimally invasive BAC 2. Lobar consolidation - Resemble that with bacterial pneumonia. - CT scans typically show air bronchograms or the CT angiogram sign. - The diagnosis of BAC may not be considered until the clinical symptoms and radiographic abnormalities fail to respond to antibacterial treatment. - Poor prognosis

3. Multifocal pulmonary nodules - A third form of BAC - Surgical resection in this setting may be associated with prolonged survival in carefully selected patients. - 7 th edition of the TNM staging system 1) the same lobe are classified as T3 2) ipsilateral nodules in another lobe of the same lung are classified as T4 3) nodules in the contralateral lung are classified as M1a

Clinical symptoms - Usually reflect the extent of disease involvement. - Patients with a solitary peripheral nodule are often asymptomatic. - More extensive tumors 1) Cough 2) Shortness of breath 3) Hemoptysis 4) Weight loss 5) Fever ( 괴사성 폐렴과는 달리 고열을 보이지는 않음 ) 6) Bronchorrhea : > 100mL/day of watery sputum  이로 인한 fluid loss 와 electrolyte imbalance 도 야기 될 수 있다. 7) Hypoxemia : V/Q mismatch 의 증가, shunt 로 fatal hypoxemia 초래.

Diagnosis and staging Solitary peripheral nodule - The diagnosis is generally established with surgery and pathologic examination of the resected tumor. - The preoperative CT radiographic appearance may provide information suggesting the diagnosis of BAC. - 종격동 림프절 확대, 원격전이 및 절제 후의 재발을 거의 보이지 않음 - CT 상 말단 폐에 focal ground glass appearance, 와 consolidation 의 혼재 로 보임. - 종양 내에 가성 공동 혹은 공기방울 음영 (bubble lucency), open bronchus sign, pleural tag 등을 동반할 수 있다.

More extensive lesions (multifocal disease or consolidation) - FNA or bronchial washing  cytology 로 pulmonary malignancy 진단 pure BAC 와 adenocarcinoma with BAC component 를 감별할 수 없지만 치료적 관점에서 볼 때 이러한 extensive state 에서는 감별을 하는 것이 의미가 없다.

Treatment The management of patients with BAC and mixed adenocarcinoma with a BAC component is similar to that for patients with other types of NSCLC at a comparable stage. Locoregional disease - Surgery is the preferred treatment for patients with stage I or II BAC. - Lobectomy, Segmentectomy > wedge resection (Stage I) - Radiation therapy 1) should be used as a part of a multimodality strategy for patients with stage III disease. 2) for patients with early stage disease who are not candidates for surgery

Systemic disease : advanced disease 1. Chemotherapy : more chemoresistant than other histolocal types of NSCLC. - The Southwest Oncology Group (SWOG) evaluated a 96-hour infusion of paclitaxel in 58 patients with BAC. Partial responses were observed in 8 patients (14 percent) and stable disease in 23 (40 percent). Median survival was 12 months. - The European Organization for Research and Treatment of Cancer (EORTC) evaluated a three-hour infusion of paclitaxel in 18 patients with BAC. Two patients had a partial response and another nine had stable disease. Median survival was 8.6 months, and one-year survival was 35 percent. 2. Small molecule EGFR inhibitors : erlotinib, gefitinib

Management of bronchorrhea 1) Corticosteroid and macrolides have been used to decrease inflammation, which may contribute to bronchorrhea. 2) Prostaglandins may play a role in increased transepithelial chloride secretion that contributes to the pathogenesis of bronchorrhea in some patients. This has provided the rationale for the use of inhaled indomethacin. 3) Octreotide has been associated with effective palliation of bronchorrhea in a patient with advanced BAC. 4) In several case reports, the use of small molecule EGFR inhibitors to control the underlying tumor has resulted in improvements in associated bronchorrhea, sometimes within 24 hours. The mechanism of action of the drugs in managing bronchorrhea may be different than its antitumor effect

Summary and recommendations Bronchioloalveolar carcinoma (BAC) is a histologic subtype of adenoca rcinoma of the lung It is characterized by peripheral location, well-differentiated histology, a lepidic growth pattern, and the potential for both aerogenous and ly mphatic spread. BAC can present as an asymptomatic solitary peripheral nodule or with pulmonary symptoms due to multifocal disease or lobar consolidation. The prognosis is generally better for any given stage of disease, compare d to non-BAC non-small cell lung cancer (NSCLC).

항생제 치료 16 일 째

추적 검사 4 개월 째 남은 우하엽 경화성 병변 PCNA 시행 Mucinous adenocarcinoma Op 시행 병기 : T3N0M0, Ⅱ B 항암치료

Taking home messege 고령의 폐렴 환자들에게 적절한 치료를 하였는데도 방사선 검사상, 호전되지 않고, 병변이 남아있는 ‘ 호전되지않는 폐렴 (non-resolving pneumonia)’ 가 있을 수 있다. 흔하지는 않지만, ‘ 호전되지 않는 폐렴 ’ 의 원인이 경화성 폐암으로 뒤늦게 진단 되는 경우도 있다. 경화성 병변으로 나타나는 세기관지폐포암의 경우 다양한 임상 증상 과 영상 소견을 보일 수 있고, 폐렴과 구분이 어려워 주의를 요한다. 경화성 폐암의 경우, 조기진단을 하면 근치적 절제가 가능하기 때문에 신속하고 정확한 검사를 시행하는 것이 중요하다. 따라서, 폐렴 환자들에서 처음 검사에서 악성 세포가 없었다고 하더라 도, 경화성 병변이 지속된다면 세기관지폐포암을 염두에 두고 신중하 게 추가 검사를 고려해야 한다.