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Introduction

In patients with hematological malignancies, the spleen is a common site of involvement (1,2). The incidence of metastasis to the spleen in patients with lung cancer has been reported to be a few percent to 21% when investigated by autopsy (3,4). By contrast, however, reports of spleen metastasis from lung cancer either at the time of initial diagnosis or during the clinical course are extremely rare (5). In the present study, the case of a patient with lung adenocarcinoma who developed isolated metastasis to the spleen following surgery is described. A review of this rare metastasis in patients with lung cancer was also conducted.

Case report

A 63-year-old woman presented with the incidental detection of a nodule 30 mm in diameter in the left lung on chest radiography, at the Mito Medical Center of the University of Tsukuba (Mito, Japan). At the age of 57 years, the patient had undergone a left mastectomy due to breast cancer; however the patient was asymptomatic and had been in good health since then. The physical examination was unremarkable. The chest computed tomography (CT) scan revealed a well-circumscribed mass in the left lower lobe of the lung that measured 30×27×18 mm with specular appearance (Fig. 1). The routine laboratory tests were normal, as were tumor markers including carcinoembryonic antigen. The patient was diagnosed with adenocarcinoma on the basis of pathological examination of transbrochial biopsy specimens. Distant metastasis was not detected. Informed consent was obtained, and the patient underwent lobectomy of the left lower lung and mediastinal lymph node dissection. The final pathological diagnosis was lung adenocarcinoma staged as pT3N2M0, stage IIIB. An EGFR exon 19 deletion was identified. Soon after the surgical resection, the patient received adjuvant postoperative chemotherapy. However, 12 months after the surgery, a follow-up abdominal CT scan revealed three nodular lesions of ≤10 mm in diameter in the spleen (Fig. 2). No metastatic lesions in the liver, adrenal gland and abdominal lymph nodes were found. The splenic nodular lesions were considered to indicate an inflammatory disease such as granuloma. However, fluorodeoxyglucose positron emission tomography (FDG-PET)/CT confirmed uptake in these nodules in the spleen, but there was no other metastatic sites (Fig. 3). The patient then underwent splenectomy. As the resected tumor had the same characteristics as the specimen of the primary lung carcinoma and was positively immunostained for thyroid transcription factor-1 and cytokeratin 7, the tumor was pathologically diagnosed as spleen metastasis from lung adenocarcinoma (Fig. 4). Thereafter, the patient received treatment with four courses of cisplatin and vinorelbine, and was well without any signs of tumor progression.

Figure 1. Chest computed tomography revealed a well-circumscribed mass in the lower lobe that measured 34×30×24 mm and had a specular appearance.

Figure 2. Follow-up abdominal computed tomography scan revealed metastatic lesions of diameter ≤15 mm in the spleen (arrows).

Figure 3. Fluorodeoxyglucose-positron emission tomography/computed tomography confirmed uptake in the nodules in the spleen. There were no other sites of metastasis.

Figure 4. (A) Primary resected lung adenocarcinoma lesion and (B) resected spleen tumor (hematoxylin and eosin staining, ×200). (C) Immunostaining of thyroid transcription factor-1 in the resected spleen tumor (hematoxylin and eosin staining, ×200).

Discussion

Although numerous cases of abdominal visceral metastases from lung cancer have been reported (6,7), metastasis to the spleen from lung cancer is considered to be rare and is usually detected only at autopsy (8,9). The early detection of metastasis to the spleen is challenging since the majority of patients are asymptomatic in the early stage of such metastasis. However, as the availability of CT scanning and ultrasonography has increased, this has enabled spleen metastasis to be diagnosed more accurately (10–12). CT scanning and ultrasonograpy can provide a quick, direct and non-invasive evaluation of spleen metastasis; however, some metastasis cannot be identified by ultrasonograpy because of the effect of air in the stomach and colon. Therefore, abdominal CT scans should be considered for use if spleen metastasis is suspected. Several studies have reported the clinical significance of FDG-PET/CT scanning in the detection of spleen metastasis from lung cancer (13–17). In the present case, FDG-PET/CT was useful for confirming the presence of malignant lesions in the spleen.

We previously evaluated spleen metastasis from lung cancer (18). In the study, 12 (1.2%) of 997 consecutive patients with lung cancer had spleen metastasis, and isolated spleen metastasis in the absence of widespread disease was considered an extremely rare event (18). All 12 cases had accompanying metastasis to other organs, including the paraaortic lymph nodes, bone, lung and liver, which also suggested a poor outcome for patients with spleen metastasis (18). Moreover, it is noteworthy that all 12 patients exhibited more than one metastatic site in the abdomen. The most common site of metastasis was the lymph nodes in the abdomen. Therefore, it was concluded at that time that spleen mass accompanying metastasis to other abdominal organs in patients with a known lung cancer should be regarded as a metastasis. We recently conducted a review of patients with lung cancer and spleen metastasis, and found 20 such patients (10–15,17,19–30). In these 20 patients, it was notable that all but 4 of the 20 patients had no abdominal metastasis other than spleen metastasis. Therefore, it should now be recognized that spleen metastasis is not necessarily accompanied by abdominal organ metastasis. The difference between our previous study (18) and the recent case reports might be due to the development of imaging modalities and the advancement of knowledge in such rare metastasis.

The incidence of spleen metastasis is considered to differ among histologic types of lung cancer (3,4,18). Small cell lung cancer has been recognized to be the most common cell type likely to metastasize to the spleen and squamous cell lung carcinoma the least likely (3,4). In our previous study of lung cancer metastasis, adenocarcinoma had almost the same frequency of spleen metastasis as small cell lung cancer (1.3 vs. 2.0%, respectively), while in squamous cell carcinoma, only 0.6% of patients developed spleen metastasis (18). When reviewing recent case reports, however, 5 of the 20 patients with lung cancer and spleen metastasis had squamous cell carcinoma (12,21,27–29). These results indicate that the spleen is a possible site to which disease may spread in patients with advanced or recurrent lung cancer, including those with squamous cell carcinoma of the lung.

With regard to the radiological classification of spleen metastasis dependent on pathological examination, there may be four types, known as solitary, multiple, microscopic and diffuse. Sardenberg et al presented three main macroscopic patterns: Macronodular, micronodular and diffuse (17). The latter two types might not be apparent in abdominal CT scans, although FDG-PET/CT scanning may detect the diffuse type of spleen metastasis. In our previous study, the solitary nodular type was the most common, and in a review of recent case reports, the solitary type was confirmed as the most common type (10,12–17,19–21,23,26). The differential diagnosis of a solitary nodule or nodules in the spleen includes several diseases, either benign or malignant (31). In differential diagnosis, FDG-PET/CT scanning can be useful to identify whether the lesion is malignant (13–17).

A mass in the spleen accompanied by metastasis to other abdominal organs in a patient known to have lung cancer or with a history of lung cancer should be regarded as a metastasis. In addition, an isolated splenic mass in the absence of abdominal metastatic disease elsewhere should also be considered likely to represent a metastasis. An isolated spleen mass identified at the initial diagnosis or during the clinical course in a patient with lung cancer should be considered for an interventional approach and can provide pathological material.

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