She was referred to our hospital because of sudden anterior chest pain. Hematology, biochemistry and blood gas analysis were normal. A chest computed tomography (CT) scan revealed a ground-glass opacity (GGO) in her left S10 lung segment (Figure ​(Figure1A)1A) which was 1.3 cm in size, and a solitary small nodule of 5 mm in diameter localized in her left S4 segment (Figure ​(Figure1B1B).

From the beginning, we suspected lung carcinoma, but we could not get our patient's consent for performing bronchoscopic examination and surgical resection. Follow-up with CT showed that the GGO size had slightly increased and that the small nodule size had not changed. We suspected that the GGO was lung carcinoma, but it was difficult to rule out whether the small nodule was a lung metastasis. If this small nodule was not lung metastasis, the lung carcinoma could have been considered as being in the early stage. We considered that pathological examination by surgical resection was appropriate because it was also an approach for treating the lung carcinoma. We performed a left lower lobectomy and an upper lung partial resection in order to make a definitive diagnosis and to decide further therapeutic strategies. The pathological diagnosis of the GGO in her left S10 segment was primary lung adenocarcinoma(localized bronchioloalveolar carcinoma; Figure ​Figure2).2). On the other hand, pathological examination of the small nodule in her left S4 showed spindle-shaped smooth muscle cells and low cuboidal metaplastic bronchiolar epithelia, surrounded by fascicles of smooth muscle cells without mitosis and nuclear atypia (Figure ​(Figure3A).3A). Immunohistochemical staining for thyroid transcription factor-1(TTF-1) and surfactant apoprotein A (SP-A) showed epithelial structures composed of alveoli or bronchioli (Figure 3B, C), suggesting that the low cuboidal metaplastic bronchiolar epithelium derived from the pre-existing bronchiolar epithelium. There was positive immunohistochemical staining for α-smooth muscle actin (α-SMA) and spindle-shaped cells (Figure ​(Figure3D),3D), suggesting that the spindle-shaped cells were smooth muscle cells. Positive immunoreactivity for estrogen receptor (ER) and progesterone receptor (PgR) suggested that the spindle-shaped cells were uterine smooth muscle cells (Figure 3E, F). Unfortunately, a histological sample of the uterine leiomyoma was not available for comparison. The small nodule was diagnosed as a BML based on the results of immunohistochemical staining and her past history of uterine leiomyoma.

Abramson et al. [2] reported that the average age of patients with BML is 48 years old, that the period from hysterectomy to nodule discovery is variable from three months to 26 years and that the first symptom of BML may sometimes be cough or chest pain although it can also be almost indiscernible. Horstmann et al. [3] reported that the radiological presentation of BML can be as multiple nodules in 87% of cases (bilateral nodules, 70% and unilateral nodule, 17%) or as a solitary nodule in 13% of cases. The main metastatic site of BML is the lung but other sites, including lymph nodes, soft tissue of the pelvis, bone, bone marrow, greater omentum, peritoneum and heart, have been also reported [4]. Tsunoda et al. [5] reported only one case of benign metastasizing leiomyoma of the lung complicated with primary lung cancer. To the best of our knowledge, there are no cases in the literature about the association between lung cancer and BML other than this report. Thus, we believe that this is a very rare case of BML associated with primary lung cancer.

Recent studies have shown that BML is caused by lung metastasis of uterine leiomyoma, which is histologically a benign tumor with a very low grade of malignancy; uterine leiomyoma has been reported to depend on sex hormones [1,6-8]. On the other hand, Patton et al. [9] have previously reported that BML results from the monoclonal, hematogenous spread of an apparently benign uterine leiomyoma. However, these conclusions are still controversial.

Pathological examination of the BML in our case showed spindle-shaped cells without mitotic activity or nuclear atypia, surrounded by cuboidal bronchiolar epithelial cells; additional immunohistochemical staining showed that the spindle-shaped cells derived from smooth muscle cells of the uterus, and that the low cuboidal metaplastic cells derived from pre-existing bronchial cells [4]. The presence of TTF-1 is usually assessed to confirm the diagnosis of primary non-small cell lung carcinoma (especially adenocarcinoma) [10]; the purpose of TTF-1 staining in our particular case was to decide whether the low cuboidal metaplastic bronchiolar epithelium observed in the pathological specimens derived from the pre-existing bronchiolar epithelium, because it is known that TTF-1 is only expressed on the normal epithelium of the lung and thyroid [10]. We believe that the diagnosis of BML is not dependent on the expression of TTF-1. Pathological comparison between the solitary pulmonary nodule and the original uterine tumor should provide confirmatory evidence but the sample was not available. However, the small lung nodule was diagnosed as BML based on the results of the immunohistochemical staining and the past history of hysterectomy for uterine leiomyoma.