Intra-abdominal sequestration of the lung and elevated serum levels of CA 19-9: a diagnostic pitfall

Abstract

Background

Extralobar pulmonary sequestration is an uncommon congenital abnormality that is rarely diagnosed after the age of 40 years. We describe a 64-year-old woman with an intra-abdominal sequestration of the lung and elevated carbohydrate antigen (CA) 19-9 serum levels.

Case outline

On abdominal ultrasound a semi-solid cystic tumour was demonstrated that showed tight connection to the tail of the pancreas according to computed tomography. Cytological examination of the percutaneous biopsy did not lead to a definitive diagnosis. CA 19-9 serum levels were repeatedly elevated >250 IU/ml. With a tentative diagnosis of a tumour of the tail of pancreas the semi-solid cystic mass was resected. Frozen section histology suggested the diagnosis of pulmonary sequestration, which was confirmed by definitive histological examination. Immunohistochemical staining of the specimen with a specific monoclonal antibody against CA 19-9 showed strong immunoreactivity. Three months later the elevated CA 19-9 serum levels returned to normal.

Discussion

Elevated CA 19-9 serum levels have been described in benign pulmonary and mediastinal cystic lesions and in one case of extralobar intrathoracic lung sequestration. Although there is evidence that malignancies may arise in congenital lung cysts, CA 19-9 serum levels have not been investigated in such cases. Based on our results elevated serum values of CA 19-9 in combination with a cystic semi-solid mass in the left subphrenic space should include the differential diagnosis of extralobar pulmonary sequestration.

Introduction

Pulmonary sequestration is an uncommon congenital abnormality characterised by the presence of non-functioning lung tissue which usually has no communication with the normal bronchial tree and which is supplied by an anomalous systemic artery instead of a pulmonary arterial branch ¹. Both the extralobar and intralobar forms probably develop from an accessory lung bud of the primitive foregut. In intralobar sequestration abnormal pulmonary tissue is incorporated within the normal lung and shares a common covering of visceral pleura. In contrast, in extralobar sequestration abnormal lung tissue is separated from normal lung and has its own pleural investment. Extralobar sequestration is usually an incidental finding on routine investigations and is predominantly diagnosed in the first decade of life. Diagnosis after the age of 40 is extremely unusual ²,³. Carbohydrate antigen (CA) 19-9 is expressed by a variety of normal and neoplastic tissues. There is evidence that unstable epithelial cells within the cyst walls may lead to premalignant proliferation and neoplasia ². We report the case of a 64-year-old woman with a cystic tumour in the left upper abdomen and elevated CA 19-9 serum values. The tumour turned out to be caused by an intra-abdominal sequestration of the lung.

Case report

In a hitherto healthy 64-year-old female patient a semi-solid cystic tumour in the left subphrenic space was picked up incidentally by abdominal ultrasound during a routine check. The patient was in good general condition and without symptoms. The abdominal ultrasound demonstrated a well-defined echogenic semi-solid tumour with multiple cystic areas. According to a computed tomography (CT) scan this lesion was in tight connection to the tail of pancreas (Figure 1). An extraluminal compression of the splenic flexure of the colon was found at colonoscopy. CA 19-9 serum levels were repeatedly elevated with >250 IU/ml (normal 35 IU/ml). Cytological examination of the percutaneous biopsy of the lesion showed fatty tissue, fibroblasts and epithelial cells without abnormalities.

Figure 1. .

Computed tomography of the lesion with puncture needle in situ. A well-defined semi-solid tumour with multiple cystic areas in tight connection to the tail of the pancreas is shown.

Surgical excision of the cystic mass was performed with a tentative diagnosis of a tumour originating from the tail of pancreas. The lesion was approximately 8 cm in diameter and had no connection to any abdominal organ but was strongly adherent to the left diaphragm. Frozen sections during the surgical intervention demonstrated lung tissue. Definitive histological examination confirmed the intraoperative diagnosis, revealing fibrous and fibromuscular tissue with embedded cartilage and ample glandular formation with cysts lined by mature respiratory epithelium consistent with the diagnosis of pulmonary sequestration (Figure 2). Immunohistochemical staining performed with a specific monoclonal antibody against CA 19-9 (clone C241:5:l:4; Novacastra, Newcastle, UK) showed a strong immunoreactivity in the epithelial lining of dilated bronchi predominately localised to the apical membrane and the cytoplasm, but also within the amorphous material inside the lumen (Figure 2, insert).

Figure 2. .

Fibrous and fibromuscular tissue with embedded hyaline cartilage and cysticaiiy dilated bronchial spaces lined by mature respiratory epithelium (haematoxylin and eosin-stoined section; ×20). Insert Positive immunostaining with an anti-CA 19-9 antibody predominantly localised to the apical membrane and the cytoplasm of the respiratory epithelium (streptovidin-biotin-technique; DAB-development; ×400).

The postoperative course was uneventful. One month after the excision of the tumour the CA 19-9 serum level declined to 232 IU/ml and reached normal values 2 months thereafter.

Discussion

Extralobar and especially intra-abdominal pulmonary sequestrations are extremely rare ³,⁴. Pulmonary sequestration was reported to occur in about 1% of 1051 adults undergoing resection of pulmonary parenchyma during a 24-year period ³. Intralobar sequestration is encountered about six times as often as the extralobar form ⁵. Usually extralobar sequestration is situated in the posterior mediastinum at the costophrenic sulcus or in the pleural cavity; however, it may be found elsewhere in the mediastinum as well as in the pericardial and peritoneal cavities, attached to the diaphragm and to the chest wall ³. In two-thirds of patients both the extralobar and intralobar forms are situated in the left pleural cavity. The abnormal arterial supply originates from the descending thoracic aorta. Congenital malformations such as diaphragmatic hernia are frequently associated with the extralobar form ³. Men are more often affected than women (3:1).

Extralobar sequestration is usually an incidental finding on routine investigation or during the management of systemic congenital abnormalities ⁴. Since sequestrations represent a spectrum of anomalies they should be described in detail, i.e. according to their connection to the tracheobronchial tree, the arterial supply, the visceral pleura and especially any associated anomalies, so as to facilitate their management ⁶.

The characteristic ultrasound appearance plus serial CT scans are helpful in the preoperative evaluation ⁷,⁸. The sequestered segments are usually of mixed attenuation on abdominal ultrasound and CT scans since they consist of normal lung elements such as alveolar parenchyma, cartilage and bronchial glands. The cysts are lined with respiratory epithelium and contain either mucus or air ³. Elevated CA 19-9 serum levels have been described in benign pulmonary and mediastinal cystic lesions as well as in one case of extralobar intrathoracic lung sequestration ⁹,¹⁰. There is evidence that malignancies arise in congenital lung cysts, but CA 19-9 serum levels have not been investigated in such cases ²,¹¹,¹²,¹³. De Perrot and co-workers evaluated the proliferative activity of epithelial cells within the cysts and stated that unstable epithelial cells lead to atypical adenomatous hyperplasia and neoplasia ². A malignant tendency of intralobar sequestration of the lung has been documented by small foci of neuroendo-crine tumours within these pulmonary sequestrations in two cases ¹⁴,¹⁵. The proliferation of pulmonary neuroendocrine cells as small tumours had probably occurred due to chronic hypoxia ¹⁴.

In the present case the radiological appearance of the tumour and the significantly elevated CA 19-9 serum levels led us to suspect a cystic tumour of the tail of pancreas and advise operation. Since extralobar pulmonary sequestrations located in the abdomen are rarely diagnosed before excision, and there is a positive risk of malignant change, prompt resection after diagnosis is justified except in patients with associated anomalies ⁶,¹¹,¹⁶.

We did not take into consideration the possibility of intra-abdominal extralobar sequestration of the lung. Preoperative aortography might have demonstrated the anomalous arterial supply from the aorta and led to a more conservative approach with radiographic follow-up. Nevertheless, we doubt that operation could have been avoided, as a cystic tumour of the pancreas could not have been definitely excluded. Finally, the immunohis-tochemical demonstration of CA 19-9 in the bronchial mucosa of the intra-abdominal lesion and the return of the elevated CA 19-9 values to normal within 3 months after its removal strongly argue for a causative link between extrapulmonary sequestration and the increased serum CA 19-9 in this case.

Based on the available data a cystic semi-solid mass in the left subphrenic space in close juxtaposition with the pancreatic tail and in combination with elevated serum levels of CA 19-9 is highly suspicious of an extralobar pulmonary sequestration of lung tissue mimicking a pancreatic tumour.