The multidisciplinary care of a woman presenting with lymphoma in pregnancy whose delivery was also complicated by placenta accreta spectrum

Abstract

We report the case of a 44-year-old presenting with breathlessness in her second trimester of pregnancy diagnosed with pulmonary diffuse large B cell lymphoma (DLBCL) which was further complicated by a placenta accreta spectrum (PAS) disorder. In pregnancy, she was treated with rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone, which was associated with neutropenic sepsis requiring admissions to the intensive care unit with respiratory compromise. She safely delivered an infant at 31 weeks but required a hysterectomy at the time for PAS and seven days ventilation on the intensive care unit post-operatively. It is the first case report of DLBCL and PAS in pregnancy.

Introduction

Pregnancy-associated Non-Hodgkin lymphoma (NHL) is rare, with an incidence of ∼2 per 10,000 females per year in the UK.¹ Diffuse large B cell lymphoma (DLBCL) comprises 48% of NHL presenting in pregnancy.² DLBCL affecting primarily the lungs is uncommon.³ There are no cases in the literature of pulmonary DLBCL presenting in pregnancy.

PAS is reported as affecting 2–90 per 10,000 births internationally, with rising incidence associated with previous caesarean section and increased maternal age. It is a serious obstetric complication and carries a high risk of haemorrhage and need for hysterectomy.⁴

We report a rare case of pulmonary DLBCL complicated by placenta accreta syndrome (PAS) during pregnancy. It shows the benefits of multidisciplinary planning, and highlights the important role of the obstetric physician in facilitating a multidisciplinary approach to pregnant women with complex medical issues.

Case report

A 44-year-old pregnant woman presented to the urgent respiratory assessment clinic at 12 weeks’ gestation with a three-week history of shortness of breath, a cough with frothy sputum and six-month history of weight loss. This was her second pregnancy, which like her first was conceived by egg donor in vitro fertilisation (required because of diminished ovarian reserve). Her first child was delivered by elective caesarean section for breech presentation. Additionally, she had a 13-year history of enteropathic arthropathy affecting her knees, ulcerative colitis and asthma. Her medications consisted of azathioprine, sulphasalazine, folic acid and inhalers. She had stopped infliximab prior to conception. Clinical examination revealed chest wall tenderness but was otherwise unremarkable. Initial investigations and their results are shown in Table 1 and Figure 1.

Table 1.

Results of investigations.

Investigation	Result
CRP	67 mg/L
White cell count	4.87 µL
Lactate	1.0 mmol/L
Creatinine	39 µmol/L
Chest radiograph	Widespread semi-confluent airspace desiccation with a slightly nodular pattern.
Arterial blood gas	PaO2 8.9 kPa (FiO2 of 0.6) Sats 95%
CT chest	Patchy consolidation and widespread pulmonary nodules throughout the lungs ranging from 2 mm to 25 mm diameter with semi-solid edges. No pulmonary embolus (see Figure 1)
Blood cultures	No growth
Respiratory viral PCR	Negative
Cytomegalovirus PCR	Not detected
Epstein Barr virus PCR	16,650 copies/mL
Epstein Barr virus DNA	4.22 log10 copies/mL
Adenovirus PCR	Not detected
Enterovirus PCR	Negative
Histology of lung nodule	High-grade diffuse large B cell lymphoma, EBV driven, most likely associated with immune suppression due to azathioprine (for ulcerative colitis)

CRP: C = reactive protein; PCR: polymerase chain reaction.

Figure 1.

Computed tomography of chest: coronal view.

She was admitted by the acute medical team, with input from an obstetric physician. A provisional diagnosis of atypical chest infection with possible underlying respiratory disease was made. High flow oxygen therapy, antibiotics and antifungals were commenced, as well as prophylactic dose of low molecular weight heparin (LMWH). She deteriorated and required admission to the intensive care unit (ICU) but failed to improve. On day 11, biopsies of the lung nodules were performed which led to the diagnosis of DLBCL. She was too unwell to have a bone marrow biopsy or imaging of the abdomen and pelvis at this point. However, extra lymphatic involvement of the lungs made it stage 4B.

Cytotoxic treatment was commenced with rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (R-CHOP). Within 48 h, she improved with reduced oxygen requirement allowing discharge to the ward. Five days post RCHOP, she required treatment for neutropenic sepsis and was commenced on granulocyte-colony stimulating factor.

Routine ultrasound scanning at 20 weeks revealed an anterior and low-lying placenta covering the previous caesarean scar. Ultrasound performed at 24 weeks’ gestation by a fetal medicine consultant experienced in diagnosing PAS, at a tertiary referral hospital, showed numerous abnormal placental lacunae on grey-scale scanning suggesting an increased likelihood of PAS. However, the colour-flow Doppler imaging performed at the same time was equivocal. A multidisciplinary discussion surrounding the merits of a magnetic resonance imaging scan occurred and it was concluded that it would not influence management.

In view of her comorbidity and abnormal placenta, a multidisciplinary team consisting of obstetricians, obstetric physician, anaesthetist, intensivist, neonatologist, interventional radiologist and haematologist collaborated to plan for her continuing pregnancy and delivery. The aim was to deliver at 34 weeks’ gestation, under combined spinal epidural anaesthesia (to avoid positive pressure ventilation), with the presence of an experienced obstetrician and gynaecologist in case of placenta accreta and with the expectation of major haemorrhage. It was decided that she would not be suitable for prophylactic iliac artery balloon catheters in view of her malignancy and the associated thrombosis risk. As she was deemed high risk for venous thromboembolism, it was decided that prophylactic dose of LMWH was to be continued until 12 h prior to delivery, only to be withheld if there was significant antepartum haemorrhage. Prophylaxis was to continue until six weeks post-delivery.

At 31 weeks’ gestation, after the fifth cycle of chemotherapy, she was again admitted and treated for neutropenic sepsis. Her respiratory function deteriorated and she required admission to the ICU. Over the next 12 h, she felt a reduction in fetal movements and fetal heart monitoring with cardiotocography was classified as suspicious. Given delivery was potentially imminent, LMWH was omitted.

In view of this deterioration, delivery was expedited. Caesarean section was performed in the general emergency theatre adjacent to the ICU. Experienced obstetricians, gynaecologists, anaesthetists and neonatologists were present. Her respiratory compromise (partial pressure of arterial oxygen (PaO₂) 11.0 kPa, fraction of inspired oxygen (FiO₂) 0.6) meant she was unable to lie flat, excluding a spinal anaesthetic. General anaesthesia was therefore used with rapid sequence induction. Large bore intravenous and arterial access was established prior to induction. Cell salvage was used from incision, and four units of fully cross-matched blood were available.

A transverse low abdominal incision was made through her previous caesarean section scar and a high transverse uterine incision was used to avoid the placenta. A female infant weighing 1753 g was delivered (with APGAR scores of 5, 8 and 10 at 1, 5 and 10 min, respectively). She required nasal continuous positive airway pressure (CPAP) and was transferred to the neonatal ICU. After delivery of the baby, the placenta appeared to be separating; therefore, to facilitate the attempt at separating the placenta, carbetocin (100 micrograms intravenously) was administered. However, separation was incomplete with associated blood loss. The team agreed that it was necessary to proceed to hysterectomy.

The uterus and placenta were examined by a histopathologist who concluded that the appearance of the uterus was in keeping with placenta accreta. Examination of the placenta could not prove or exclude placenta accreta but was suggestive of it.

Intraoperatively, the woman was challenging to ventilate. Pressure controlled ventilation was used with peak pressure 30 cmH₂O and peak end expiratory pressure 8 cmH₂O. Her oxygen saturations were maintained at greater than 92% with FiO₂ 0.7, and arterial sampling showed PaO₂ 15.5 kPa and PaCO₂ 8.4 kPa (end tidal CO₂ 6.9 kPa). Estimated blood loss was 1800 mL, and 403 mL of cell salvaged blood was returned and one unit of packed red cells was given. Bedside coagulation testing with rotational thromboelastometry showed a normal coagulation profile. Tranexamic acid 1 g was administered intravenously.

Post-operatively, she was transferred back to the ICU sedated and ventilated. Adult respiratory distress syndrome was diagnosed and treatment included muscle relaxation, diuresis and prone ventilation strategies with no improvement. Cardiovascular instability developed and large doses of noradrenaline were required. Antimicrobial treatment was instituted with voriconazole, acyclovir, meropenem and clarithromycin.

One week after delivery, she was commenced on high-dose methylprednisolone (1 g intravenously) and over the next 48 h her respiratory function improved. She was extubated three days later, and discharged home three weeks after delivery. She was advised not to breastfeed due to the chemotherapy. Her daughter was weaned from CPAP support and allowed home at three weeks of age.

Computed tomography imaging after seven cycles of RCHOP showed some small pulmonary nodules and the cause of these remains unclear, although they have not progressed on repeated imaging. Mother and daughter remain well two years later and have been discharged from paediatric follow-up.

Discussion

MBRRACE states that when cancer is suspected in pregnancy it should be investigated in the same way and time scale as for non-pregnant women; however, risk to the fetus versus benefit should be considered and discussed with the woman to determine the appropriate pathway of investigation.

MBRRACE also highlights the importance of discussing any pregnant woman who attends the emergency department, with a medical problem, with the maternity medical team.

This case shows the importance of confirming a diagnosis as soon as possible – once the lung biopsy had been reported, appropriate treatment could be instigated and improvement in the woman's condition ensued.⁵

This case also demonstrates the importance of multidisciplinary team work. Meeting face-to-face with other specialties to plan the management of complex medical obstetric cases is instrumental in promoting safe and collaborative care.

In a pregnancy complicated by multiple issues involving many specialists, an obstetric physician can be key in facilitating the multidisciplinary care but also being the constant in the patient journey, having continuous input from presentation to discharge, and were invaluable in this case.