Over the 19-year study period, 25 patients were primarily diagnosed and treated at or referred to our facility for PBML. Two patients were excluded due to male patient (n=1), or slides were not available for review (n=1). 5 patients were followed up no more than 6 months, their baseline characteristics were described and analyzed, but their follow-up data were not included.
The clinical characteristics Of the 23 patients are shown in Table 1. The median age at diagnosis was 46 years (range, 36-62 years). Seven patients (30.4%) were identified as postmenopausal. Nineteen patients (82.6%) had a history of uterine leiomyoma; 2 patients (8.7%) had no history of uterine leiomyoma and 2 patients (8.7%) did not exam for it. Of 19 patients with history of uterine leiomyoma, 16 patients (84.2%) had undergone at least one surgical procedure for uterine leiomyoma prior to diagnosis of PBML, with the median time from the first gynecologic surgery of 10.5 years (range, 2-15 years), and 3 patients had no surgical history. Thirteen patients (56.2%) were identified with pulmonary tumors due to their respiratory or other symptoms such as cough (n=7), short of breath (n=3), chest pain (n=1), backache (n=1) and bloating (n=1). The other 10 patients (43.8%) were incidentally detected by chest imaging procedures done for other reasons such as health care examination (n=9) or follow-up after thyroid cancer (n=1).
All lesions were identified by chest CT. Multiple pulmonary nodules were identified in 18 patients (78.3%), of which 17 patients with bilateral diseases (Fig 1A，patient 13) and 1 with unilateral diseases. There were 4 patients (17.4%) with solitary PBML nodules (Fig 1B, patient 7)，and 3 of them were postmenopausal. There was 1 patient had multiple cystic diseases (Fig 1C, patient 12). In addition, PET-CT scan was performed in 11 patients (47.8%) and showed no uptake or only mild uptake of 18F-FDG(Fig 2, patient 23), with a median SUV of 2.0 (range, 1.5-3.8). Clinical physical examination and radiologic images revealed apparent extrapulmonary diseases in 3 patients (13.0%) including disseminated peritoneal leiomyomatosis (n=1), pelvic retroperitoneum mass (n=1), and pelvic retroperitoneum mass accompanied with left medial thigh muscle mass (n=1).
All 23 patients had undergone surgical procedures of pulmonary nodules for diagnosis including biopsy, wedge resection and lobectomy. 4 patients underwent thoracotomy, 8 patients underwent video-assisted thoracoscopic surgery (VATS), and 11 patients were diagnosed by Computed tomography–guided biopsy. One patient with left medial thigh muscle mass simultaneously underwent biopsy of both lung and left thigh muscle. Pathologic findings in all tissue samples met diagnostic criteria of BML. Four patients (17.4%) with solitary PBML nodules underwent a curative surgical resection (3 patients with wedge resection and 1 patient with left pneumonectomy because the mass was in the left main bronchus). The historic and operative characteristics are provided in Table 2.
Additional treatment strategy including close observation, surgical castration, medical castration with gonadotropin-releasing hormone analogs (GnRHa), estrogen receptor antagonists (tamoxifen), or aromatase inhibitors (letrozole). After surgical resection of PBML, 14 patients considered observation，5 patients underwent bilateral salpingo-oophorectomy, and 4 patients selected adjuvant medicine treatment. Of 14 patients with observation, only one patient (patient 10) had hysterectomy and bilateral salpingo-oophorectomy because of symptomatic uterine leiomyoma and progression of PBML after 8 years. All Of 5 patients with bilateral salpingo-oophorectomy had a close observation and no disease progression. Of 4 patients with adjuvant medicine treatment, 3 patients received GnRHa injections (3.75mg/month) and 1 patient took letrozole (2.5mg/day). 2 of 3 patients with GnRHa finally had bilateral salpingo-oophorectomy because their pulmonary nodules shrinked after injections but grew again after stop the medicine. Patient 17 was the most special one; she had 6 doses of GnRHa injections after diagnosis of PBML. Shortly after stopping GnRHa, the size of PBML grew slowly again, and then she underwent laparoscopic bilateral salpingo-oophorectomy. The tumor shrinked subsequently. However, bilateral pulmonary nodules on radiographic surveillance were enlarged again 3 years after surgical castration. Since then, she has been taking letrozole 2.5mg oral daily and achieved again PR 6 months after medical treatment. To the date of writing the manuscript, she has still been under treatment.
Because 5 patients were followed up no more than 6 months, their follow-up data was not included. At a median follow-up of 8 years (range, 1-18 years), 4 of 18 (22.2%) patients achieved CR, 3 (16.7%) patients achieved PR, 9 (50%) patients had SD, and 2 (11.1%) patients had PD. The clinical characteristics between patients achieved CR+PR and SD+PD were compared in Table 3. Only the characteristics of pulmonary lesions showed a significant difference between the two groups. For the 4 patients with CR (median follow-up: 11.75 years), all of them had single nodule in lung and received curative surgical resection without additional therapy. For the 3 patients achieved PR (median follow-up: 2 years), all of them received surgical castration. Of 9 patients with SD, 6 patients had only a careful observation with a median follow-up for 1.5 years (range: 1-17 years), 2 patients underwent surgical castration (8 and 11 years of follow-up), and 1 patient took letrozole for 1 year. For the 2 patients with PD, patient 14 was young and preserved her ovaries. She was followed up for 4 years, her lesion was stable at the first 3 years and grew in the past year, she chose to continue close observation because she had no symptom; patient 8 had 9 injections of GnRHa, her pelvic and pulmonary lesions grew after stopping the medicine, then she underwent bilateral salpingo-oophorectomy and surgical excision of pelvic retroperitoneum mass. She is now 6 months after the last surgery; the nodules in her lungs are stable for now.
Interestingly enough, after being diagnosed of PBML, 9 premenopausal patients preserved their ovaries at first, with the median age of 43 years (range, 36-51years). Among them, 6 patients had close observation and 3 received GnRHa injections. Finally, only 3 patients (patient 8、10 and 17) underwent bilateral salpingo-oophorectomy during 1 year, 2.5 years and 8 years of follow-up, respectively.