Benign pulmonary metastasizing leiomyomatosis in pregnancy: a rare complication after cesarean section

Benign metastasizing leiomyoma (BML) was first reported by Steiner in 1939 (1) as a rare tumor of benign histologic appearance, well-differentiated smooth muscle cells and dense connective tissue in the lung. Association with typical uterine leiomyomas has clearly been shown (2,3). Very recently, it has been confirmed that BML correlates positively with a history of previous hysterectomy for uterine leiomyoma (4). Because both benign uterine and pulmonary tumors have been found to depend on the estrogen and progesterone status, their growth is mainly retained to be hormone dependent (5). Therefore, hormone-level changes such as pregnancy and menopause might have important effects on the general course of the disease. We report a case of BML in a woman with a history of multiple uterine fibroids whose pregnancy was complicated by recurrent chest infections, pre-eclampsia and intrauterine growth retardation (IUGR). A 31-year-old caucasian woman (gravida 2, para 1) underwent hysterectomy plus oophorectomy for multiple uterine fibroids associated with pulmonary metastasizing leiomyomatosis 6 months after a lower segment cesarean section (LSCS). She was followed in her second pregnancy, and multiple uterine fibroids were only detected on an early ultrasound scan when she was referred for a pelvic mass compatible with 20–22 weeks gestational size uterus. A history of recurrent chest infections treated with antibiotics was recorded throughout this pregnancy. Serial sonographic monitoring during the pregnancy revealed the fibroids to have grown, while the fetus showed evidence of IUGR. At 30 weeks' gestation, she was admitted to the antenatal ward with evidence of pre-eclampsia such as dipstick proteinuria, raised blood pressure (143/100 mmHg compared with 112/76 at the booking visit) and mild headache. From then on, she was closely monitored as follows: 4-hourly blood pressure, daily urinalysis, pre-eclampsia toxicosis blood, 24-h urinary collection, and daily cardiotocography. Steroid prophylaxis (Betamethasone 12 mg i.m. twice 12 h apart) was given and hypertensive treatment (Methyldopa 250 mg oral 8 hourly) was started as required. At 31 weeks' gestation, a deteriorating condition characterized by persistent high blood pressure, severe headache, proteinuria, presence of visual disturbances and absent end diastolic flow at the fetal Doppler studies, prompted us to perform an emergency LSCS. A LSCS was performed under spinal anesthesia using a 27-gauge Whitacre needle. The operative findings showed a central necrotic fibroid (˜7 cm) in the corpus of the uterus and a highly abnormal lower uterine segment that was riddled with enlarged multiple fibroids and distended veins. An alive-active female infant was delivered as breech and immediately admitted to the special care baby unit where she required supplemental oxygen and antibiotics for mild respiratory distress syndrome (RDS). Maternal blood pressure was quite stable throughout the surgery. An estimated blood loss of 1000 mL was promptly replaced by 1000 mL of colloid and 2 units of blood. A magnesium sulfate infusion was started after LSCS for 24 h. The patient was then transferred to the delivery suite for routine postoperative management. Approximately 4 h postcesarean section, she was looking quite pale and started to complain of tiredness, increasing chest pain and breathlessness. Oxygen saturation was 95% on 4 L/min oxygen. Both anesthetist and medical opinions were requested. On auscultation of the chest, bilateral basal inspiratory crackles were present. Arterial blood gas analysis showed: pH 7.41, PaO2 8.7, PaCO2 4.29, base excess −2.4 mmol/L, and bicarbonate 20.7 mmol/L. A chest X-ray was arranged to rule out an amniotic fluid embolism, pulmonary embolism, pneumothorax or pulmonary edema. After two consecutive chest X-rays showing a picture of fluid overloaded, the presence of innumerable discrete pulmonary nodules was clearly revealed in both lung fields (Fig. 1). Subsequently, a chest computerized tomography (CT) was performed. This confirmed the same picture as the X-ray and showed no mediastinal lymphadenopathy. At that stage, the differential diagnosis laid between primary or metastatic pulmonary malignancy and miliary tuberculosis. A bronchoscopy using a flexible fiber-optic system with biopsy and bronchial washing was also performed. Cytopathology of the bronchial washing showed an appearance suspicious of malignancy, but no granulomata were seen. Conversely, no malignant cells were found in the microscopy of the salivary sputum. The histopathology of the lung samples showed several scattered well-demarcated nodules composed of smooth muscle bundles without cellular pleomorphisms or mitotic activity. These features were collectively consistent with the entity known as BML. Extensive nodular shadowing throughout both lungs. The lesions are diffuse with no zonal predominance. Once the final diagnosis was made, Medroxyprogesterone acetate 150 mg daily was started in an attempt to shrink the pulmonary leiomyomata. Within 1 week from the diagnosis the respiratory symptoms had improved significantly, and she was discharged 3 days later. Further visits were planned routinely. The Medroxyprogesterone acetate was stopped and gonadotrophin-releasing hormone (GnRH) analogue at a dose of 3.6 mg was given monthly for six consecutive months in order to shrink the uterus before proceeding to hysterectomy ± salpingo-oophorectomy. A chest X-ray done 4 months later demonstrated persistent appearance of bilateral lung nodularities. A total abdominal hysterectomy with left salpingo-oophorectomy was performed 6 months after delivery. Previous right salpingo-oophorectomy was noted at the time of surgery. She was routinely seen in medical and gynecologic clinics to assess her progress, but no additional treatment was recommended. Chest X-ray still showed pulmonary nodules 4 months after surgery, but she was without pulmonary complaints, and her spirometry test remained quite stable. The same radiographic and clinical findings were reported throughout the next 12 months (Fig. 2). Twenty months after surgery, she was completely asymptomatic and lung function showed no major impairment despite the persisting extensive radiologic abnormalities. Due to the absence of any further pulmonary symptoms, we decided to continue with medical and chest X-ray follow-ups. Thirty-two months after surgery, she was clinically well with no new evidence of progression of disease on chest X-ray. Widespread nodules throughout both lungs, which are essentially unchanged in comparison with the previous examination. BML is a rare condition characterized by the occurrence of benign smooth muscle tumors, most often located in the lung, in association with uterine leiomyomatosis. This condition may present in women of any age with uterus leiomyoma. Bachman and Wolff (2) reported that metastasizing leiomyoma occurs in women between 36 and 64 years old, while Horstmann et al. (6) found that it occurs in women between 30 and 74 years old. Although few cases of BML may be associated with respiratory symptoms such as dyspnoea, cough and chest pain, most of them are generally asymptomatic and diagnosed coincidentally by routine chest X-ray done for other reasons. As previously reported, the clinical appearance of BML varies from chronic inactive appearance to rapid progression leading to respiratory failure and death (2). The typical radiographic appearance of this benign condition shows multiple pulmonary nodules similar in appearance to malignant disease or miliary pattern (7). Either microscopic intravascular spread of tumor cells or multifocal independent proliferation of smooth muscle tissue has been believed as a pathogenetic hypothesis of BML. The present case report seems to sustain the former hypothesis as the most likely. Although multiple uterine fibroids were present throughout all of the pregnancy, the clinical situation precipitated suddenly after emergency LSCS. Collectively, this evidence together with a recent report (4) shows as the primary source for the pulmonary metastases to be the uterus, but hematogenous spread of tumor cells may occur when surgery is performed. Both to shrink the uterine leiomyomas before surgery and to improve the respiratory symptoms, Medroxyprogesterone acetate first and GnRH anologue after were administered. In accordance with other authors, hormone-dependent treatment produced pulmonary function improvement and leiomyomas regression (3). Considering the uterus as the primary site for the metastasizing process (3), and known the efficacy of surgical castration in this tumor (8), a hysterectomy with a salpingo-oophorectomy was performed. While pulmonary nodules were constantly present after surgery, no obvious growth of the multiple lesions as well as deteriorating clinical findings were observed in our as well as in other hands (4). To our knowledge, this is the first case in literature that reports BML as a life-threatening event in association with a pregnancy already complicated by pre-eclampsia and IUGR. Only Horstmann et al. (6) had previously described a case of BML in a pregnant woman. In contrast to our case, although these authors also pointed out the hormonal dependence of this condition, they reported a spontaneous regression of pulmonary nodules during pregnancy and puerperium. The difference between the two reports could lie on the mode of delivery, in fact, while the woman in the present case had an emergency cesarean section, the women in the case reported by Horstmann et al. had a spontaneous vaginal delivery. This evidence further supports the higher risk of BML after a surgical procedure of the uterus. In conclusion, we retain that when persistent pulmonary symptoms are presenting together with a history of multiple uterine fibroids during pregnancy, although rare, a diagnosis of BML should be considered amongst the differential diagnoses of breathlessness after LSCS. A prompt diagnostic management by chest X-ray and CT, bronchoscopy and transbronchial biopsy should be addressed as mandatory. Finally, when possible, a combination of medical and surgical treatment has to be considered as an effective therapeutic plan for the regression of the benign tumors and improvement of the pulmonary function in case of BML. Address for correspondence: Luciano G. Nardo Department of Obstetrics and Gynaecology Wexham Slough Berkshire SL2 4HL UK e-mail: lnardogyn@hotmail.com