Bronchioloalveolar Carcinoma in African Americans

Posted by James

INTRODUCTION

Lung cancer is the leading cause of cancer related deaths in the United States among both men and women. There were 164,100 new cases and 156,900 deaths estimated for 2000. Nonsmall-cell lung cancer accounts for 80% of all cases, with the remaining 20% presenting as small-cell cancer. Adenocarcinomas are subdivided histologically into four subtypes; acinar, papillary, mucinous, and bronchio-alveolar carcinoma (ВАС).

ВАС is the least common but most controversial primary malignant pulmonary neoplasm. More than 1,200 cases of ВАС have been reported in the literature. The incidence of squamous cell carcinoma is decreasing because of reduced smoking in men, whereas the incidence of adenocarcinoma is increasing. Most of this is attributed to the increasing incidence of ВАС from 4-20% in recent years. The pathogenesis is unclear, and pathologic distinction from adenocarcinoma is arbitrary. Nevertheless, ВАС is generally considered a distinct entity. Its diffuse form was described by Malassez in 1876 in a patient discovered at autopsy to have a bilateral, multinodular, malignant tumor originating in the lung and confined to the thorax. In 1903, Musser characterized the pneumonic variant. They were variously designated as carcinomapneumonia, bron-chiolar carcinoma, alveolar cell carcinoma, or pul­monary adenomatosis. Because of multiplicity of nomenclature, it was difficult to assess the relative incidence over the years as reported differently by different investigators. In 1960, Liebow introduced the term “bronchioalveolar carcinoma.”
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Currently, diagnostic criteria are: presence of no other primary adenocarcinoma, no central bronchial source, no disruption of the pulmonary interstitial structure, and growth of malignant cells lining the alveolar septa. The etiology of ВАС is unknown. Commonly, it is associated with scars from previous tuberculosis, prior inflammatory processes, other pulmonary infections, and idiopathic fibrosis. Whether scar formation stimulates epithelial proliferation, which may initiate the malignant transformation, or fibrosis is a tissue response to a tumor itself is not settled.

The name ВАС implies an uncertain origin. Origins from type-2 pneumocytes, Clara cells, and bronchiolar mucous cells have been hypothesized. The multicentricity is poorly understood, and it seems that multiple nodular variant is probably due to aerogenic and lymphatic dissemination. Alternatively, multiple tumors may develop concomitantly. Jaagsiekte is a retrovirally mediated form of pulmonary adenomatosis in sheep. It is characterized initially by proliferation of alveolar cells and eventually by a malignant tumor similar to ВАС. Transmission from animals to humans has not been documented, but ВАС has been detected in patients exposed to infected sheep. Intranuclear inclusions have been noted, but a virus has not been detected. Microscopically, the tumor cells appear as tall columnar or cuboidal cell proliferation that fills the adjoining alveoli, often with papillary formations. The cells may rest on the stroma of distant air spaces and project into the lumen in a saw-toothed fashion. The underlying lung parenchyma shows integrity of interstitial framework and alveolar septa. Mucus is usually scanty or absent in the cuboidal, papillary, or irregular epithelial types. Some cytologic atypia may be present. The cells are more often cuboidal and may be gigantic or bizarre in papillary forms. Multicentric lesions represent advanced disease rather than multicentric origin. The progression occurs along the airways and/or by aerosolization or tumor emboli. This may be the reason for better survival observed in patients with multiple unilateral diseases than in those with bilateral lesions, implying that unilateral lesions represent extensive local disease, whereas bilateral lesions represent metastatic disease. Infrequently, localized ВАС may progress to diffuse disease or metastasize to regional lymph nodes or distant sites. Though diffuse ВАС generally carries a relatively poor prognosis regardless of the histologic subtype, some patients can live for years with slowly progressive disease. The natural history and prognosis of metastatic ВАС is similar to or worse than that of other lung cances. Koga et al. from Japan have recently noted clinicopatho-logical and molecular evidence indicating the independence of ВАС components from other subtypes of human peripheral lung adenocarcinoma.
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The evaluation and management of ВАС is similar to that of other types of lung cancers. CT scan will detect more multicentric lesions than the chest x-ray. Mediastinoscopy is not routinely recommended because of low incidence of lymph node metastases. Bronchoscopy is usually not helpful, as most of the lesions are peripherally located and are not intrabronchial. However, advanced disease is more amenable to biopsy. Patients with unilateral disease should undergo resection if otherwise in good health, including those with multiple unilateral lesions. At surgery, complete lymph node assessment must be done. Thereafter, patients should be assessed every four-to-six months for two years, then annually. Evaluation should include physical examination, chest x-ray, sputum cytology, and serum chemistry. Pulmonary resection should be considered for recurrent ВАС, although long-term survival seems unlikely. Like in other forms of lung cancers, patients who have Tl disease (<3 cm) fare better than those with T2 disease (>3 cm).

Earlier reports suggested that metastatic ВАС is resistant to radiation and chemotherapy. Only symptomatic and supportive care was recommended. Feldman et al. showed that metastatic ВАС and adenocarcinoma had similar clinical manifestations, chemotherapeutic response, and prognosis. The overall chemotherapeutic response rates were 32% for metastatic ВАС and 33% for metastatic adenocarcinoma. The responses were usually limited. Recurrence develops in 30-40% of patients during long-term follow-up. Most of the recurrences are within five years, and patients have been found to live for an extended period of time after recurrence. Thus, the natural history of ВАС is different from other cancers in that its progression is slower. Dumont et al. reported that the natural history of ВАС is especially influenced by its nodular or diffuse nature, vascular invasion, and aerogenous spread. From 29 institutions of the SWOG (Southwestern Oncology Group), 53 previously untreated patients with stage-3b/4 ВАС were entered into a phase-2 trial with Paclitaxel 140 mg/m²/cycle by 96-hour infusion every three weeks. Of 43 currently evaluable patients, 12% had partial response, and 40% showed stable disease. tadalis sx 20

Median survival was 10 months, with a 45% one-year survival after registration at the time of reporting this study. Recently targeted systemic therapy, such as the epidermal growth factor receptor inhibition with tyrosine kinase inhibitors, has been shown to have remarkable activity against ВАС. Earlier, Pestana et al. reported growth inhibition of adenocarcinoma cells by antibodies against epidermal growth factor receptor and ganglioside GM3. In this study we reviewed the clinical and pathophysiological features of ВАС in African Americans.