Renal cell carcinoma in pregnancy

Although rare in women of childbearing age, renal cell carcinoma is the commonest renal neoplasm occurring in pregnancy¹ and is potentially curable with prompt diagnosis and treatment. However, the symptoms can mimic more common disorders such as urinary tract infection.

CASE HISTORIES

Case 1

A woman aged 28, gravida 2, para 1, was referred for evaluation of a right renal mass at fourteen weeks' gestation. She had no previous history of hypertension, renal disease, or pre-eclampsia. The mass had been detected after onset of right flank and loin pain, and hypertension of 150/90 mmHg, at twelve weeks' gestation. Urinalysis, urea, electrolytes and creatinine were normal. Urine cytology was negative. Renal ultrasonography revealed a 10 × 6.5 × 7.4 cm solid mass with heterogeneous echotexture arising from the lower pole of the right kidney.

After extensive counselling and consulation with obstetric staff, it was decided that she should undergo a right radical nephrectomy, which was performed at seventeen weeks' gestation. She received standard perioperative antibiotic prophylaxis, and in addition low-molecular-weight heparin and a twenty-four-hour infusion of the tocolytic β-agonist ritodrine. Postoperatively she recovered without incident and was discharged on day seven. The remainder of the pregnancy was uneventful. She was induced at forty weeks' gestation for worsening hypertension, and gave birth to a healthy boy weighing 2.5 kg.

On histopathological examination the surgical specimen contained a grade II clear-cell renal carcinoma, with a maximum diameter of 9 cm. Pathological staging was T2 N0 Mx. The patient remains well with no evidence of recurrence at twelve months' follow-up.

Case 2

A woman of 24, gravida 1, para 0, was referred at twenty-three weeks' gestation for assessment of episodic haematuria. She had no relevant medical history. Microscopic haematuria had been detected at her antenatal booking visit at twelve weeks' gestation. Microbiological culture was negative at that time and no further evaluation was performed until twenty-four weeks' gestation when she was referred with right loin pain and episodic frank haematuria. A full blood count and urea, creatinine and electrolytes were normal. Renal ultrasonography revealed a well-defined 5 cm solid mass arising from the medial aspect of the mid to lower part of the right kidney. An ultrasoundguided biopsy was taken but the cytopathological appearances did not allow certain differentiation between an oncocytoma and a well-differentiated renal cell carcinoma. The urine contained atypical epithelial cells consistent with renal cell carcinoma. Further evaluation by magnetic resonance imaging confirmed the presence of a mass with an intermediate signal and slight heterogeneity. There was no evidence of surrounding soft tissue invasion or of retroperitoneal lymph node enlargement.

After further obstetric consulation, she underwent a right radical nephrectomy at twenty-five weeks' gestation. Preoperatively she received prophylactic corticosteroids to reduce the likelihood of neonatal respiratory distress syndrome, should she deliver before term. She also received indometacin as a tocolytic agent. Initial postoperative recovery was uneventful; however, she did experience symptoms suggestive of preterm labour on the sixth postoperative day and was treated with an infusion of ritodrine for twenty-four hours. Her symptoms settled and she was discharged. She subsequently underwent induction of labour at forty weeks' gestation and a 3.3 kg boy was delivered by emergency caesarean section for fetal distress.

Histopathological examination revealed a grade I renal cell carcinoma. There was no invasion of the renal capsule. There has been no evidence of recurrence at 5 years' follow-up.

COMMENT

Although renal cell carcinoma accounts for 3% of all adult malignancies, it is rare in women of childbearing age. To date there are reports of about fifty cases diagnosed during pregnancy: it is the most common renal neoplasm reported in pregnancy, accounting for half of all primary tumours¹. Sex and age matched data do not exist to allow comparison of the relative proportion occurring outside of pregnancy, although in general terms there is no evidence of an increased incidence of malignant neoplasms in pregnancy².

Pregnancy and cancer are the only two biological conditions in which antigenic tissue is tolerated by a normally functioning immune system. However, there have been no demonstrable immunodeficiencies in pregnancy to antigens carried by tumour cells³. Furthermore, in most cases the biological behaviour of malignancy is not influenced by pregnancy, with the possible exception of a small subgroup of hormonally sensitive malignant melanomas⁴. With breast cancer, although it seems to present at more advanced stages in pregnancy, the prognosis of each stage is similar to that in non-pregnant women⁵.

In 1986, Walker and Knight¹ reviewed the presentation of renal cell carcinoma during pregnancy and found that the commonest presenting symptoms of such tumours were a palpable mass (88%) and pain (50%). Haematuria and hypertension accounted for 47% and 18% of cases, respectively. A subsequent review has suggested that there has been a change in the presentation of renal cell carcinoma in pregnant women, with diagnosis now more frequently made incidentally during ultrasound examination performed for other reasons⁶. In addition, urinary tract symptoms are experienced by many pregnant women and are often due to non-neoplastic causes, such as calculi or urinary tract infection. Similarly, hypertension, especially during the third trimester, is often induced by pregnancy and related to pre-eclampsia. This means that renal cell carcinoma may not be considered as a potential cause for such symptoms, thus leading to delay in diagnosis and treatment.

Diagnostic evaluation of the pregnant patient with possible renal carcinoma requires special consideration of non-invasive techniques and as little radiation exposure as possible to mother and fetus. As a first step, urine should be sent for cytological analysis. In non-pregnant patients intravenous pyelography (IVP) and abdominal CT are the modalities frequently employed in the evaluation of renal tumours, but there is no proven safe threshold dose of radiation exposure to the fetus⁷. Abdominal ultrasound along with magnetic resonance imaging (MRI) can adequately identify, differentiate between, and stage solid renal masses in most cases, and with their avoidance of radiation exposure to the fetus these are the investigations of choice.

Indeed, ultrasound has a similar sensitivity (85%) to that of IVP and CT for renal masses greater than 3 cm, and is much more sensitive than IVP for renal masses between 2 and 3 cm (82% v 52%)⁸. Renal radionucleotide scans, being associated with less radiation exposure than routine X-ray films, have been used to determine function of the contralateral kidney and intrinsic activity. They do, however, pose additional risks to the fetus from the passage of radiopharmaceuticals and contrast agents across the placenta. As an alternative, doppler assessment of the contralateral kidney may be employed.

There are several issues to consider when treating a pregnant woman with a solid renal mass that is suspicious for malignancy. First, the clinician's primary responsibility is to the mother, though management must take into account her wishes regarding the welfare of the fetus. Secondly, such cases should be managed in a multidisciplinary setting involving urologists, obstetricians, neonatologists, radiologists, histopathologists and oncologists. Thirdly, the standard surgical treatment of most stages of renal cell carcinoma is a radical nephrectomy, involving the en bloc removal of the entire kidney and perinephric fat within Gerota's fascia. This has been performed via both transperitoneal and extraperitoneal approaches. The small numbers of reported cases of renal cell carcinoma in pregnancy allow few conclusions to be drawn regarding the outcomes of each. However, avoidance of disruption of the peritoneal cavity in the extraperitoneal approach may theoretically be associated with less uterine irritation and in turn fewer obstetric complications, including preterm labour.

The timing of surgery is guided by the biological behaviour of such tumours and neonatal survival rates for different gestations. The doubling time of a renal cell carcinoma is estimated at 300 days⁹. Certain considerations should be made when embarking on surgery in pregnant women. Non-obstetric surgery is performed in approximately 1 in 500 pregnancies¹⁰. When surgery is performed during the first trimester there is an increased risk of preterm labour with its associated problems of fetal prematurity. However, with the improvements in neonatal care, fetal survival rates continue to increase and although actual figures vary between different neonatal units, neonatal survival rates of over 90% can be expected beyond twenty-eight weeks' gestation. Therefore, it is recommended that surgery should not be delayed in the first and third trimesters. However, if a mass is diagnosed in the second trimester then it is reasonable to wait until fetal viability before proceeding to surgery.