Precursor Lesion of BAC

Definition: When lung tissue resected for cancer is examined carefully, small, single or multiple, proliferative lesions, 1-7 mm in diameter, can often be found away from the main tumor, which is usually, but not always, adenocarcinoma. The lesions have been designated bronchioloalveolar cell adenoma or atypical adenomatous hyperplasia (AAH) of unknown malignant potential, and are believed to be precursor lesions of BAC [1].

Histologically, the lesions are not encapsulated and not associated with scarred lung. Atypical epithelial cells line alveolar walls that show variable thickening. Larger lesions show more cytologic atypia than smaller ones.

Here, at higher magnification, epithelial cell nuclei show random orientation in the cytoplasm, slight hyperchromaticity, and irregularity in shape. By immunohistochemistry, many of these cells are type II cells. A nuclear vacuole, characteristic, but not diagnostic of type II cells, is present at the arrow.

Histologic Features of AAH

Behavior: Because there is subjectivity in separating AAH from metastasis of the primary, especially a primary BAC, a study comparing outcomes of patients with primaries accompanied by AAH, primaries without AAH, and primaries with metastases in the same resection was performed. The patients with AAH in their resected lungs had the same survival as those without, but patients with metastases in the resected lungs had a worse outcome for the same stage of the primary tumor [6]. This study suggests that a histologic distinction between AAH and metastatic tumor can be made. It does not clarify the significance of AAH as a precursor to cancer.

Another lesion confused with bronchioloalveolar carcinoma: Bronchiolization seen in diffuse fibrosis of the lung can resemble BAC.

The spread of respiratory epithelium from bronchioles (B) to line air spaces in scarred, inflamed lung is called bronchiolization. Although the pattern can resemble BAC, ciliated cells--extremely rare in BAC--are usual, and squamous metaplasia, not found in BAC, is frequent. Cells are not enlarged and N/C ratios are normal. Squamous metaplasia is present at the lower right.

References

1. Miller R. Bronchioloalveolar cell adenomas. Am J Surg Pathol 1990; 14:904-912.

2. Carey F, Wallace W, Fergusson R, Kerr K, Lamb D. Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases. Thorax 1992; 47:1041-1043.

3. Nakayama H, Noguchi M, Tsuchiya R, Kodama T, Shimosato Y. Clonal growth of atypical adenomatous hyperplasia of the lung: cytofluorometric analysis of nuclear DNA content. Mod Pathol 1990; 3:314-320.

4. Kitamura H, Kameda Y, Ito T, Hayashi H, Nakamura N, Nakatani Y, Inayama Y, et al. Cytodifferentiation of atypical adenomatous hyperplasia and bronchioloalveolar lung carcinoma: immunohistochemical and ultrastructural studies. Virchows Arch 1997; 431:415-424.

5. Kitamura H, Kameda Y, Nakamura N, Nakatani Y, Inayama Y, Iida M, Noda K, et al. Proliferative potential and p53 overexpression in precursor and early stage lesions of bronchioloalveolar lung carcinoma. Am J Pathol 1995; 146:876-887.

6. Suzuki K, Nagai K, Yoshida J, Yokose T, Kodama T, Takahashi K, Nishimura M, et al. The prognosis of resected lung carcinoma associated with atypical adenomatous hyperplasia. A comparison of the prognosis of well-differentiated adenocarcinoma associated with atypical adenomatous hyperplasia and intrapulmonary metastasis. Cancer 1997; 79:1521-1526.

Discussion

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