Management of atypical complicated abdominal masses in the second trimester of pregnancy.

An obese woman, with a body mass index of 33, in her 40s, G1P0A1, came to our attention during the second trimester of pregnancy (21 weeks of gestational age, GA) for severe and acute abdominal pain located at the upper left quadrant and the pelvis (Visual Analogue Scale=5 for both sites) associated with mild dyspnoea. Her first and second trimester routine screening reported a low risk for aneuploidies (confirmed at the non-invasive prenatal testing) and a regular fetal morphology. First, she was admitted to the emergency room for a thorough multidisciplinary evaluation: she had normal oxygen saturation (median value 97%), a physical examination of the thorax revealed a normal heart rate (median value 74 bpm) and blood pressure (median value 100/60 mm Hg). The ECG was normal. Then, she was transferred to the Obstetrical and Gynaecological Division. The abdomen seemed to be more enlarged than expected for the gestational age, with a tender swelling and a taut-elastic mass occupying all the upper left quadrant, measuring 18 cm, without clinical signs of ascites. The bimanual vaginal examination showed the presence of a fixed mass in the lesser pelvis of about 9 cm, rounded and hard, that partially bulged at the posterior fornix. Analgesic therapies (paracetamol 1000 mg intravenously two times per day) and semi-orthostatic position, hypothetically limiting the diaphragmatic compression from the pregnant uterus and enormous abdominal masses, slightly decreased the symptoms without any supplemental oxygen or ventilation support, reducing pain from 5 to 1 according to the Visual Analogue Scale. During the hospital stay, the patient developed a low-grade fever. So, a PCR for severe acute respiratory syndrome, Coronavirus 2 nasopharyngeal swab was performed, showing a negative result; on the contrary, a Klebsiella pneumoniae infection was detected in urine samples. Moreover, the blood test showed a status of iron deficiency anaemia with haemoglobin (Hb) 9.9 g/L (n.v. 12.0–16.6 g/L) and serum ferritin of 25 mcg/L (n.v. 15–300 mcg/L); a slight increase of C reactive protein with a value of 1.39 mg/dL (n.v. 0–0.3 mg/dL); and an increase of the neutrophilic count (white blood cells 11.29×103 /uL (n.v. 4–10×10 3  /uL) with neutrophils 9.27×10 3  /uL (n.v. 2.8–5.5×10 3  /uL)), consistent with pregnancy-related changes.

After the surgery, the worsening anaemia (Hb 7.5 g/L, HCT 24.3%), together with the persistence of the iron deficiency, required intravenous iron supplementation (ferric carboxymaltose 1 g) and two blood transfusions with success (Hb 10.0 g/L, HCT 30.4%). The patient was discharged without complications 10 days after the surgery and entered an obstetrical strict follow-up every 3 weeks, showing fetal growth (86th percentile, according to the WHO fetal growth chart calculator, available online at https://srhr.org/fetalgrowthcalculator/ #/), and amniotic fluid index. The peritoneal fluid was negative for both cultural and cytological tests. The pathological examination revealed the presence of benign uterine leiomyomas, areas of ischaemic necrosis near the twisted pedicle. The caudal myoma would have represented a huge obstacle for the fetal head progression during the expulsive phase of labour. Thus, an elective caesarean was performed on the same surgical scar as soon as the fetus reached 37 weeks of gestation, minimising the risk of uterine scar rupture with an excellent neonatal outcome. The patient does not currently report symptoms related to myoma, even though the size of the residual pelvic myoma has slightly reduced to 7.5 cm. The patient has been breastfeeding well, but she prefers to be unscheduled for the next surgical step due to the partial postpartum regression of the residual leiomyomas, the absence of symptoms and the fulfilment of motherhood. The baby is growing up well.

Due to the worsening of clinical conditions (mass-related abdominal pain and restrictive lung disease dyspnoea due to the size of the abdominal masses), the necessity of a conclusive diagnosis, the risk for complications 4 (rupture, torsion and infection), and the prospect of uterine enlargement along with fetal growth, the patient underwent laparotomy with a longitudinal xiphos-pubic cut at 21 w+6 d after informed consent. First, we collected two samples of the free peritoneal fluid for cultural and cytological purposes. Then, we explored the abdominal cavity, verifying the presence of fetal cardiac activity. Surprisingly, the cranial mass was a huge pedunculated, atypical cystic and taut-elastic leiomyoma of the uterus, highly vascularised, initially twisted and leaking, probably justifying the fever during the hospital stay (see figure 2 ). Therefore, the surgical team decided to excise the mass from its uterine implant gently using a double clamp (see figure 2 ). Once the stalk was cut, the exposed root was carefully closed with a single absorbable suture. The caudal mass, originating from the uterine torus, was left in situ to minimise obstetric risk. This mass appeared fixed, with a smooth surface and soft texture like a large cystic intramural-subserosal leiomyoma. The surgery lasted 2 hours and 25 min. Notably, the patient received progesterone prophylaxis 100 mg intramuscularly, starting intraoperatively and then continuing 100 mg intramuscularly per day until discharge. After that, the patient received an intramuscular caproate hydroxyprogesterone (341 mg 1 fl intramuscularly every 3 days, as reported on the package leaflet) until the elective delivery. Intraoperative antibiotic prophylaxis with cefazolin 2 g intravenously was followed by postoperative antibiotic treatment with cefazolin 1 g intravenously three times per day + clarithromycin 500 mg two times per day during the hospital stay according to the urine culture’s antibiogram (Klebsiella pneumoniae highly sensitive to cephalosporins and clarithromycin).

The diagnosis and management of atypical or symptomatic abdominal masses during pregnancy present significant clinical challenges. Diagnostic options are limited to clinical examination, ultrasound (US) with colour Doppler and non-contrast MRI. Preoperative US is particularly valuable in identifying symptomatic uterine leiomyomas located along the anterior wall of the gravid uterus, whether submucosal or pedunculated. 1 MRI offers superior diagnostic accuracy for multiple, large, intramural or posterior leiomyomas, as it can precisely determine the distance between the myoma and the uterine cavity. 1 The diagnostic role of serum tumour markers during pregnancy remains under debate. 2 Notably, CA-125 levels physiologically rise during the first trimester and subsequently normalise. 2 3 Therefore, isolated measurements are not diagnostic, while serial evaluations can provide useful trends for differential diagnosis and follow-up. 2 3 Optimal management requires careful multidisciplinary risk assessment to balance obstetric risks with the rarity and complexity of these clinical scenarios.

Myomas can often be misdiagnosed as adnexal masses: the incidence during pregnancy is 0.3–10.1% and 1–6%, respectively . 1 3 In the present case, the initial evaluation showed the abdominal masses that appeared as two huge decidualised endometriomas, except for the caudal solid component of the pelvic mass that seemed like a posterior intramural-subserosal myoma of the uterus with cystic degeneration of 58×71 mm at both US and MRI imaging. In the absence of definitive management guidelines for pelvic masses in pregnancy, the multidisciplinary team considered that elective surgery could be associated with a decreased risk of preterm delivery. 1 During the pregnancy, the serum CA-125 usually reaches two peaks, one in the first trimester (median 23 U/mL, p<0.00001) and the other one in the third trimester of pregnancy (median 21 U/mL, p<0.001) compared with those in the second trimester (median 14.0 U/mL) 5 ; on the contrary, the present case showed a value of 41.8 U/mL, higher than the median value during the second trimester. CA-125 is mainly used as an oncological marker for ovarian cancer (standard current cut-off ≥35 U/mL), especially in over-50-year-old women (higher area under the curve, positive predictive value, sensitivity and specificity), even though it can relate to many benign conditions such as endometriosis and adenomyosis (>19 U/mL), pelvic inflammatory disease, menstruation, early and near-term pregnancy (median 23 and 21 U/mL, respectively), risk of miscarriage and also myoma (cut-off <19 U/mL). 5 7 The key elements that oriented the clinical decision were the presence of huge and vascularised masses with mixed (solid and cystic) components with an actual risk of complication (rupture/torsion/infection), the clinical condition (worsening pain and dyspnoea), possible mass’ growth with a higher chance to go through hypoxia, necrosis and degeneration, 8 the slight positivity of oncological markers (CA-125=41.8 U/mL), and the space limit to guarantee further uterine physiological enlargement. Due to the possible tumorous origin and the uncertain origin of the masses, the patient also underwent an MRI without contrast for better diagnostic accuracy after the ultrasound examination. According to the up-to-date recommendations, the gadolinium-enhanced MRI should not be performed during pregnancy, unless strictly necessary, due to rheumatological, inflammatory or infiltrative skin conditions, risk of stillbirth or neonatal death. 9 Therefore, the multidisciplinary team performed the non-enhanced MRI, avoiding more than 1.5-T MRI, considered reasonably safe after the first trimester. 9 In this instance, the multidisciplinary team comprising surgeons, gynaecologists and obstetricians opted to proceed with longitudinal laparotomic surgical management subsequent to obtaining a designated written informed consent from the patient. The superior one exhibited a pedicle at the time of surgical assessment, thereby presenting a significant risk for an acute, typical complication. This constituted the rationale for limiting the procedure to the upper myomectomy. Furthermore, serial and intermittent transvaginal ultrasounds monitored fetal viability throughout the operation, supported by the prophylactic administration of intraoperative progesterone. According to a large multicentric study conducted by Zhao et al , it is mandatory to check and document the fetal heart rate before, during and after the surgery. 10 Usually, the surgical management is delayed until after birth, preferring a medical and expectant approach, 3 even if Sakinci et al conducted a recent study in a tertiary centre which showed that there were no statistically significant differences between the group of women who underwent caesarean section (CS) plus myomectomy compared with patients without myoma who underwent only CS in terms of preoperative and postoperative Hb values or blood transfusion rates (p >0.05); however, hospitalisation and surgery duration were significantly higher in the group that underwent CS myomectomy (p =0.001 and p =0.001, respectively). 11 The mean myoma size was 8.3 ± 4.1cm with a statistically significant and positive correlation between myoma size and hospital stay (p =0.01). 11 The same research study also showed a statistically significant and inverse correlation between the size of the myoma and the delivery week (p = 0.035). 9 Uterine leiomyomas follow a non-linear trend of size changes during pregnancy and puerperium. 12 In detail, the size of leiomyomas increases by 6.90% every week: 6.12% (p<0.001) between the first and second trimesters and 3.10%±0.39% between the second and third trimesters (p<0.05). 13 Therefore, the growing trend of uterine leiomyomas during pregnancy is significantly higher during the first trimester 12 13 than in later gestational ages. Inversely, the size of myomas in the third trimester and 6 weeks after the delivery significantly decreased (mean value 44.25%±36.05%, p<0.05). 13 These papers showed the importance of an accurate US examination of the size, location, number and distance of uterine myomas from the placenta before the surgical approach. 3 5 In the case of uterine myomas diagnosed during pregnancy, conservative treatment is usually preferred to a surgical approach, due to the risk of severe bleeding, pregnancy loss, preterm labour and uterine rupture. However, myomectomy should be considered in cases of complicated masses with torsion of pedunculated myoma or persistent symptoms without benefits from conservative treatment. 14 The surgery must be as short as possible for preserving the pregnancy and it can be performed also with a laparoscopic approach, preferably with an open Hasson technique in case of lower gestational age (first and early second trimester), smaller volume of the mass and specific site (not intramural) of the myoma. 14 This approach guarantees a better outcome in terms of maternal morbidity and vaginal birth. However, the present case shows a common situation of bias selection in preferring the laparotomy to laparoscopic approach in the case of bigger, numerous, intramural or critical locations which can correlate with a higher rate of CS, due to a huge myoma adherent to the posterior wall of the isthmic site of the uterus that would have behaved as an obstacle to vaginal birth. I am a patient of the gynecology team of this hospital, and I am alive thanks to them. I live in a town far from this hospital and when I went by ambulance to the various hospitals in the province, as my case was complicated, I was advised to go to this hospital. Regarding the entire team of the gynecology department, I can only say that they are all exceptional and that they have all been close to me. They thoroughly studied my case to manage it. They were precise in everything and I entered a strict follow-up program of weekly clinical evaluation. I feel safe with them. The chief surgeon and all the doctors on his staff became my angels. Thanks to them, I am here to tell you about my experience. Thanks to them, my little girl managed to survive and come into the world. Mum and her baby will be grateful to them for life. Massive symptomatic abdominal masses in pregnancy require detailed physical and imaging assessment using bimanual examination, expert ultrasonography and non-contrast MRI. Surgical management is reserved for cases with oncological suspicion or complications such as torsion, rupture or intractable pain. Laparotomy is preferable after the late second trimester to minimise obstetric risk.

At the US evaluation, the cystic neoformations mimicked two huge decidualised endometriomas, while the caudal cyst appeared adherent to an intramural-subserosal leiomyoma of the posterior uterus wall measuring 58×71 mm. MRI showed two rounded, unilocular adnexal cysts with hypertrophied vessels and inhomogeneous fluid content (see figure 1 ): the caudal mass seemed adherent to a posterior intramural-subserosal myoma of the uterus with cystic degeneration of 58×71 mm. Due to the ‘steric bulk’ of the pregnant uterus and the huge masses, no connective stalk and/or tumour-feeding vessel was identified for the upper mass, orienting the diagnosis toward ovarian masses, especially endometriomas, due to the slight positivity of CA-125 during the second-trimester pregnancy (see discussion). Based on sonographic and MRI features, differential diagnoses included decidualised endometriomas and cystic degenerating leiomyomas: the slight elevation of CA-125 favoured endometrioma for the upper cyst, but the continuity with uterine tissue suggested myomatous origin for the caudal mass. Dyspnoea was attributed to mechanical compression from the massive abdominal lesions, without evidence of pulmonary or cardiac dysfunction.

Ultrasound imaging demonstrated two large, unilocular cystic masses with regular margins and peripheral vascularisation. The upper mass measured 18×12×7 cm, extending from the left subphrenic region to the uterine fundus. The lower mass measured 9.5×8× 8 cm and appeared adherent to a posterior intramural-subserosal myoma with cystic degeneration (58×71 mm). Tumour markers (CA 19–9, CA 15–3, CEA, β2-microglobulin and LDH) were within normal limits, whereas CA-125 was elevated (41.8 U/mL; normal <35 U/mL), showing an increasing trend from 36 U/mL 2 weeks earlier. Therefore, there was a slight increasing trend in the serum concentration of this marker. So, the patient underwent an MRI exam without contrast medium, which showed thick walls (1.4 cm), T1 and T2 fat-sat weighted inhomogeneous fluid content and focal hyperintense T1-T2 weighted solid components (see figure 1 ; only T2 fat-sat images were shown). The cleavage of the caudal mass was not clear, and it seemed to be in continuity with the posterior leiomyoma that had already been examined at the US evaluation. No adenopathy was identified at the MRI examination.