Adenocarcinoma in situ in type I congenital pulmonary airway malformation

Introduction

Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation, is a rare developmental malformation of the lower respiratory tract, due to abnormal branching morphogenesis. ¹ Type I CPAM is the most common form. ² Malignant transformation in longstanding cases of type I CPAM is extremely rare. ³ We present the case of a 28-year-old patient with mucinous adenocarcinoma in situ of the lung characterized by the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in type I CPAM.

Case report

A 28-year-old man presented with a 2-month history of cough with expectoration and occasional fever. He had suffered these episodes on and off for many years but never sought medical help. Chest radiography showed a large cyst in the right lower zone (Figure 1). Computed tomography showed a large cavity in the right lower lobe of the lung, measuring approximately 7 × 8 × 7 cm (Figure 2), with an eccentric mass lesion in the anterolateral wall. There was no mediastinal or hilar lymphadenopathy. Infective cyst and bronchogenic cyst were in our differential diagnoses. A right lower lobectomy was performed via an open thoracotomy (Figure 3). Histopathology of the resected lung specimen showed a large cyst lined by ciliated columnar epithelium with underlying fibroblastic tissue. Pulmonary parenchyma around the cyst showed tall columnar mucinous epithelium extending along the alveolar spaces in a lepidic pattern, and mucoid material within some adjacent alveoli (Figure 4, Figure 5). The tumor was positive for cytokeratin-7 and negative for cytokeratin-20, thyroid transcription factor-1, napsin A, and CDX2 on immunochemistry. Histopathology and immunohistochemistry were consistent with a diagnosis of mucinous adenocarcinoma in situ arising in type I CPAM. Mutation testing showed a missense mutation in codon 12 of the KRAS gene. The patient had an uneventful postoperative period and was advised follow-up every 6 months.

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Figure 1.

Chest radiograph showing a large air-filled cystic lesion in the right lower zone.

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Figure 2.

Computed tomography showing a cavity in the right lower lobe with an eccentric mass lesion in the anterolateral wall.

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Figure 3.

Intraoperative photograph showing the opened cavity in the right lower lobe of the lung (arrows).

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Figure 4.

The cystic spaces lined by ciliated epithelium and alveoli lined by tall columnar mucinous epithelium. Hematoxylin and eosin stain, original magnification ×100.

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Figure 5.

The alveolar space lined by mucinous epithelium. Hematoxylin and eosin stain, original magnification ×400.

Discussion

In 1977, CPAM was classified into three types by Stocker and colleagues. ³ In 2009, two subtypes were added to the Stocker classification: type 0 and type IV. Type 0 is the rarest and most fatal form, involving the entire lung. Type I is the most common CPAM arising from distal bronchi or proximal bronchioles and involving a single lobe of the lung with a single cyst of 2–10 cm in diameter. Adjacent alveoli are usually normal. Longstanding lesions may rarely undergo malignant transformation with adenocarcinoma in situ. Type II comprises multiple cysts of 0.5–2 cm in diameter. Type III consists of very large cysts that can involve an entire lobe or several lobes of the lung. Type IV lesions have cysts with a maximum diameter of 7 cm and are often associated with pneumothorax and infection. They are strongly associated with malignancy, especially pleuropulmonary blastoma. ⁴

Adenocarcinoma in situ in association with type I CPAM was first described in 1953. ⁵ Very few cases have been reported so far. CPAM is usually distributed equally between the right and left lungs, and most often occurs in a lower lobe. ⁶ Patients usually present with cough, hemoptysis, and recurrent lower respiratory tract infections. Adenocarcinoma in situ develops in approximately 1% of unresected cases of type I CPAM. ⁷ As in our patient, it is usually discovered incidentally in cysts resected during adolescence or adulthood. It arises from the mucinous bronchiolar cells and alveoli, with a noninvasive growth pattern and pure alveolar distribution (lepidic growth). A KRAS mutation has been reported in mucinous adenocarcinoma of the lung in patients with CPAM. ⁸ It represents an early event in carcinogenesis and is associated with a poor prognosis. When detected, surgical management is indicated for type I CPAM. The rationale of surgical management is to eliminate the risk of malignant transformation and infection. Lobectomy is the preferred surgery. We present this case because of its rarity.