A 38-year-old female was diagnosed with papillary adenocarcinoma of the thyroid gland following a fine-needle aspiration biopsy in Kansai Medical University Takii Hospital in July 2009. However, a CT scan of the chest revealed the presence of multiple nodules of varying sizes in each of the lungs (Fig. 1A). Consequently, an 18-FDG-PET/CT scan was performed. A lesion with high 18-FDG uptake [maximum standard uptake value (SUV_max), >4.9] was observed in the left lobe of the thyroid gland (Fig. 1B and C). However, the results revealed that none of the pulmonary nodules demonstrated 18-FDG uptake (SUV_max, <1.6; Fig. 1C and D). To elucidate whether the pulmonary nodules were metastatic, a CT-guided needle biopsy of the lungs was performed.

Histological examination was performed as part of routine clinical practice. Briefly, the 7-µm thick sections obtained from formalin-fixed and paraffin-embedded tissues were used for further examination. Resected tissue was fixed in 10% formalin neutral buffer solution (Muto Pure Chemicals Co., Ltd., Tokyo, Japan) at room temperature overnight. Hematoxylin and eosin (H&E) staining was used according to standard clinical histological examination. Light microscopy (BM43/DP27, original magnification, ×400; Olympus Corporation, Tokyo, Japan) was used for observation. H&E staining was performed with Tissue-Tek DRS Slide Stainer (Sakura Fine Tek Europe B.V., Flemingweg, Netherlands) according to manufacturer's protocol. Immunohistochemical staining for αSMA and Ki-67 was performed with Histofine Histostainer 36A (Nichirei Biosciences Inc., Tokyo, Japan) using primary antibodies against αSMA and Ki-67 according to manufacturer's protocol.

The 4 µm thick sections obtained from formalin-fixed and paraffin-embedded tissues were deparaffinized in xylene and rehydrated in a graded series of alcohol to water. Antigen retrieval was performed using 10 mM citrate buffer (pH 6.0) at 121°C for 15 min. Sections were washed in TBS. Antigen retrieval was not performed when examining the expression of αSMA. Sections were blocked with 3% H₂O₂ at room temperature for 10 min and then incubated for 1 h at room temperature with the antibodies against αSMA (catalog no. 712021; clone no. 1A4; pre-diluted working solution for Histostainer) or Ki-67 (catalog no. 718017; clone no. SP6; pre-diluted working solution for Histostainer) (both from Nichirei Biosciences Inc., Tokyo, Japan).

The sections were subsequently incubated with the Histofine Simple Stain MAX PO (Nichirei Biosciences Inc.) for 30 min at room temperature according to the manufacturer's protocol. Staining was visualized by adding 3,3′diaminobenzidine (K5007; Dako; Agilent Technologies, Inc., Santa Clara, CA, USA) for 10 min at room temperature. Sections were counterstained with haematoxylin for 1 min and then dehydrated with a series of alcohols and xylene.

The lung biopsy tissue specimen revealed a disordered arrangement of spindle-shaped tumor cells (Fig. 2A), and immunohistochemical examination indicated that the cells stained positive for α-smooth muscle actin (α-SMA). The Ki-67 ratio was <1% (Fig. 2B and C). These findings were consistent with the phenotypic characteristics of benign leiomyoma (1). At the age of 37, the patient had experienced extensive genital bleeding due to a uterine myoma, and an emergency total hysterectomy with a right oophorectomy was performed. Histological examination of the preexisting uterine myoma tissue specimens, which were obtained during a previous surgical resection (Japan Community Health Care Organization Hoshigaoka Medical Center, Osaka, Japan), was performed as aforementioned. The results of the histological examination revealed the presence of intravascular leiomyomatosis, which is associated with the pathogenesis of PBML (4). Thus, a definitive diagnosis of PBML was established.

As the pulmonary lesions were not attributable to metastases of thyroid cancer, the patient underwent a subtotal thyroidectomy with a curative intention. The tumor-node-metastasis classification pathological stage of the tumor was identified to be pT1aN1aM0 (5). With regard to PBML, observation without the use of aggressive therapy is recommended when the tumor is clinically quiescent (3).

A 62-year-old post-menopausal female was referred to Kansai Medical University Takii Hospital for an investigation due to the presence of numerous pulmonary nodules detected in a routine chest radiography in August 2013. The patient had experienced bilateral upper back pain for two weeks prior to the first appointment at this hospital. The patient had no history of uterine myoma. A chest CT revealed the presence of a tumor in the right upper lung that was 60 mm in diameter and numerous nodular lesions of varying sizes in each of the lungs, in addition to a soft tissue mass that was 70 mm in diameter in the left second rib (Fig. 3A). The parameters assessed included complete blood count and standard clinical laboratory examinations, and the expression levels of specific tumor markers were within normal limits, including carcinoembryonic antigen, serum cytokeratin-19 fragments and Pro-gastrin-releasing pepetide. Contrast-enhanced magnetic resonance imaging of the head revealed a tumor in the left parietal lobe that was 20 mm in diameter, with an edema. As the patient was suspected to have a lung cancer with pulmonary, bone and brain metastases, an 18-FDG-PET/CT scan was performed. The results indicated abnormally high 18-FDG uptake in the right upper lung tumor, the left third rib tumor, atlas vertebra, fourth thoracic vertebra, bilateral ilia and multiple bilateral pulmonary nodules in the lungs (Fig. 3B-D; SUV_max, 20.1). Subsequently, a CT-guided needle biopsy of the right upper lung tumor was performed. Histological examination of the lung biopsy tissue specimen revealed a disordered arrangement of spindle-shaped tumor cells with mild atypia (Fig. 2D). Immunohistochemical examination revealed that the cells stained positive for α-SMA (Fig. 2E). By contrast, CD34, S-100, estrogen receptor (ER) and progesterone receptor (PgR) expression was not detected in these cells. The Ki-67 ratio was <1% (Fig. 2F). These findings are consistent with the phenotypic characteristics of benign leiomyoma. In order to confirm the pathological diagnosis, an additional CT-guided needle biopsy of the tumor of the left rib was performed. The results of the second biopsy tissue specimen from the tumor of the left rib corroborated the findings from the first biopsy specimen obtained from the tumor in the right lung. Consequently, a definitive diagnosis of PBML was established. The patient received whole brain irradiation followed by palliative irradiation for the pulmonary nodules in the right upper lung and left second rib. However, no treatment response was observed and the tumors were identified to be growing (Fig. 4). After three months, the patient was re-admitted to hospital due to a consciousness disorder. Corticosteroids and glycerin were administered, and the neurological symptoms were temporarily improved. However, the patient succumbed to septicemia with Clostridium perfringens.