Renal cell carcinoma treatment during pregnancy: Histopathological findings suggestive of rapid tumor growth.

INTRODUCTION: Diagnosis of renal cell carcinoma during pregnancy is rare. We report a case of renal cell carcinoma during pregnancy with rapid growth. CASE
PRESENTATION: A 39-year-old woman presented to our hospital for treatment of renal tumor at 22 weeks gestation. The tumor had a cystic lesion with a partition and showed rapid growth from 28 mm to 32 mm over a period of 4 weeks. The tumor was diagnosed as renal cell carcinoma and an open partial nephrectomy was scheduled at 26 weeks gestation. The operation and perioperative course were successful. Pathological findings confirmed the tumor to be clear cell renal cell carcinoma with G2 > G3, Fuhrman grade 2, pT1a, negative surgical margin, and positive detection of progesterone receptor.
CONCLUSION: We reported the successful management of a patient who was diagnosed with renal cell carcinoma during pregnancy. We also had a suggested association between rapid growth tumor and progesterone based on histopathological analysis of the tumor.

caesarean section

hand assisted

Laparoscopic

not available

partial nephrectomy

robot‐assisted partial nephrectomy

renal cell carcinoma

radical nephrectomy

We experienced the successful management of a patient with RCC during the antenatal period. The association between rapid tumor growth and progesterone receptor based on histopathological analysis of the tumor was suggested.

Introduction

Although a diagnosis of cancer during pregnancy is rare, approximately one in every 1000 pregnant women is diagnosed with cancer during the prenatal period.1 Among urological tumors, RCC is the most common during pregnancy.2 We describe a case of RCC during pregnancy and speculate about rapid growth of the tumor, based on unique pathological findings.

Case presentation

A 39‐year‐old woman presented to the former hospital due to abnormal findings in her right kidney during an ultrasound on a physical examination. At the time, she was 18 weeks pregnant. The ultrasound findings comprised a heterogeneous, well‐demarcated mass at the middle pole of the right kidney with an approximate diameter of 28 mm (Fig. 1a). Magnetic resonance imaging revealed a multifocal cystic renal mass at the middle pole (Fig. 1b). The initial treatment plan was observation, followed by resection after birth. However, the tumor increased in size by 4 mm over a period of 4 weeks (Fig. 1c). Thus, the patient was recommended to undergo resection, and was referred to our hospital.

Figure 1

(a) Abdominal ultrasound revealing a heterogeneous, well‐demarcated mass with an approximate diameter of 28 mm at the middle pole of the right kidney at 22 weeks of gestation. (b) Magnetic resonance imaging coronal view revealing a multifocal cystic renal mass at the middle pole. (c) Abdominal ultrasound revealing a heterogeneous, well‐demarcated mass with an approximate diameter of 32 mm at the middle pole of the right kidney at 26 weeks of gestation.

Fine‐needle biopsy was performed to rule out benign tumors, such as mixed epithelial and stromal tumors. The pathological diagnosis was RCC. As the tumor showed definite growth, we chose to perform resection after discussion with the patient, as well as our anesthesiology and obstetrical services. At 26 weeks’ gestation, right open PN was performed. We chose a retroperitoneal approach in the left lateral position with fetal monitoring because we thought it to be important to perform the procedure safely in a conventional procedure. If symptoms of premature labor were observed in association with the operation, administration of a uterine contraction inhibitor was considered. The surgery was successfully completed without any problems for the patient or fetus. Compared to typical PNs, the vessels around the kidney were well‐developed; thus, more careful manipulations were needed. The patient recovered well and was discharged on postoperative day 5. Pathological examinations showed clear cell RCC, G2 >G3, Fuhrman grade 2 (Fig. 2b) with progesterone receptor expression and without estrogen receptor expression (Fig. 2c). The patient delivered her baby naturally without further complications at 40 weeks’ gestation.

Figure 2

(a) Specimen. (b) Pathological identification of the lesion as clear cell RCC. (c) Progesterone receptor immunostaining showing partial positivity (Allred score 2 + 2 = 4). Magnification: ×20.

Discussion

To date, there have been 24 reported cases of RCC during pregnancy (Table 1). Generally, young people exhibit translocation RCC, but the manifestation differs in pregnant patients, such that most reports of RCC during pregnancy have been the clear cell type. In these past cases, surgeries were performed in early pregnancy and the sizes of the tumors have all been >4 cm. In 21 of 24 cases (88%), RN was performed, with eight cases (33%) receiving laparoscopic surgery.

Table 1

Details of cases in which pregnant patients were diagnosed with RCC

Reference	Year	Age	Laterality	Tumor size	Treatment	Pathology	Mode of delivery
O'Connor et al.	2004	34	Lt.	3.5 cm	Lap.RN	N/A	Spontaneous delivery
Sainsbury et al.	2004	30	N/A	N/A	Lap.RN	N/A	Spontaneous delivery
Ceglowska et al.	2006	N/A	Rt.	N/A	RN	N/A	CS at the 38th week
Van Vasten et al.	2006	30	Lt.	6.5 cm	Lap.RN	Clear cell type	N/A
Casella et al.	2007	N/A	Lt.	N/A	RN	N/A	N/A
Stroup et al.	2008	52	Lt.	6 cm	Lap.RN	Clear cell type	CS at the 33th week
Simon et al.	2008	N/A	Rt.	N/A	RN	N/A	Aborted
Van der Veldt et al.	2008	20	N/A	N/A	N/A	N/A	N/A
Lee et al.	2008	39	N/A	14.5 × 12 × 17 cm	Lap.RN	Clear cell type	Spontaneous delivery
Buda et al.	2008	N/A	N/A	N/A	RN	N/A	CS at the second trimester
Sung Yul Park et al.	2008	36	Lt	3.8 cm	RAPN	Conventional type	N/A
Fynn et al.	2009	33	Rt.	12 × 14 cm	RN	N/A	CS at the 26th week
Bovio et al.	2009	20	N/A	5.5 × 4.5 × 3.5 cm	RN	Xp11.2 translocation	N/A
Pearson et al.	2009	N/A	Rt.	N/A	RN	N/A	CS at the 26th week
Stojnic et al.	2009	22	N/A	N/A	RN	N/A	N/A
Armah et al.	2010	26	Rt.	N/A	RN	N/A	CS at the 34th week
Bettez et al.	2011	28	N/A	9.3 cm	RN	N/A	CS at the second trimester
Yin et al.	2013	32	N/A	N/A	Lap.RN	N/A	Spontaneous delivery
Katayama H et al.	2014	46	N/A	N/A	RN	N/A	CS at the 26th week
Zsolt Domjan et al.	2014	32	Lt.	6.1 × 4.1 cm	HALLap.RN	Chromophobe cell type	Spontaneous delivery
Daniel Ramirez et al.	2016	35	Rt.	7.5 cm	RAPN	Chromophobe cell type	Spontaneous delivery
Murat Binbay et al.	2016	34	Rt.	6 × 6.5 × 6.5 cm	Lap.RN	Clear cell type	CS at the 36th week
Efe C Ghanney et al.	2017	37	Rt.	7.1 × 11 cm	RN	Clear cell type	CS at the 30th week
Ercan et al.	2018	36	Rt.	12 × 9 cm	RN	N/A	CS at the 38th week
Pesent case	2018	39	Rt.	3.5 × 3 × 3 cm	PN	Clear cell type	Spontaneous delivery

Several considerations are needed for pregnant patients with RCC. First, radical or PN must be chosen. Second, the approach should be determined: open, laparoscopic, or robotic. Although minimally invasive approaches are becoming more standardized, it is important to assess individual conditions, such as gestational week, abdominal status, the effects of pneumoperitoneum on the fetus, and tumor status (size, position, and growth speed).

If surgery is deemed necessary during pregnancy, collaboration with obstetricians and anesthesiologists is needed. Regarding anesthesia, close attention is needed to avoid hypoxia, hypotension, and the use of nonsteroidal anti‐inflammatory drugs. Notably, extended hypoxia and hypotension can lead to fetal death. Regarding obstetrics, it is important to plan for possible emergency delivery of the fetus, depending on the outcome of surgery.3

Regarding the timing of resection, it can be performed safely in the first trimester for patients who are diagnosed early. Surgeries during the second and third trimesters require additional precautions to prevent uterine contractions. Uterine manipulation and hypotension should be avoided because these negatively affect uteroplacental perfusion during this period.3 Buda et al. postponed RCC resection until 28 weeks’ gestation (threshold of lung maturation).4 In the present case, the tumor showed particularly rapid growth; thus, we thought that surgery was needed, despite the pregnancy.

RCC in pregnant patients seems to be heterogenous; each patient demonstrates differences in tumor size, status, and growth. Appropriate treatment options should be discussed with patients. Even with a plan of observation, careful follow‐up is needed with frequent ultrasound examinations to check whether the tumor shows rapid growth.

As for the rate of growth, Chawla et al. reported a mean growth rate of 0.28 cm/year in a meta‐analysis of 286 renal masses at a median follow‐up of 32 months.5

This case showed faster growth than this average speed. We were considered that this rapid growth was derived from tumor aggressiveness. When we planned the postnatal surgery, it could be estimated up to more than 50 mm at the end of pregnancy. However, clear cell RCC even with grade 2–3 usually is less likely to demonstrate 4 mm growth within 4 weeks. We supposed to the relationship between pregnancy and the tumor rapid enlargement.

There might be two reasons for the rapid growth of the tumor in the present case. First, the volume of circulating blood increases during pregnancy, which may influence tumor growth. Consistent with this, intraoperative findings of blood vessels revealed greater dilation than that typically observed. Second, changes in the levels of estrogen and progesterone during pregnancy could aid tumor growth. In general, estrogen and progesterone reach to a high peak during pregnancy. Though the direct relationships between the estrogen/progesterone level and RCC are controversial,6, 7, 8, 9, 10, 11 several reports support that the change of estrogen and progesterone was related to the growth of RCC.6, 7, 8, 9, 10 However, to our knowledge, there have been no report about the histopathologically proven finding between estrogen/progesterone receptor and RCC.

In this case, we performed histopathological evaluation of estrogen and progesterone receptor expression with the hypothesis that the interaction with hormonal change and receptor expression in the tumor would affect the tumor growth. This could have contributed to the rapid tumor growth in this case. However, further studies are needed to confirm our hypothesis.

Conflict of interest

The authors declare no conflict of interest.