Isolated ureteral extrauterine endometrial stromal sarcoma: an unusual presentation

Abstract

Extrauterine endometrial stromal sarcomas (EUESSs) are rare tumours occurring without primary uterine involvement. They are classified as primary or secondary, depending on uterine involvement by stromal sarcomas. A 56-year-old woman who earlier underwent bilateral modified radical mastectomy for adenocarcinoma and total abdominal hysterectomy for endometrial stromal sarcoma, followed by tamoxifen therapy, presented with left loin pain. On evaluation, she had a left renal calculus with hydroureteronephrosis. Before percutaneous nephrolithotripsy, ureteroscopy revealed a polypoidal mass that was diagnosed as EUESS. The mass arose primarily within the ureteral lumen, with periureteric tissue uninvolved. She underwent left radical nephroureterectomy with adjuvant hormonal treatment. This is probably the first case of EUESS arising de novo from within the ureteral lumen without endometriosis, to be reported in medical literature. Immunohistochemistry facilitates earlier diagnosis. Cytoreductive surgery is the definitive treatment and multidisciplinary approach helps in overall survival of the patient.

Background

Endometrial stromal sarcomas (ESSs) are rare malignancies involving the endometrium of the uterus. They account for 15%–25% of all uterine sarcomas and 0.2% of all malignancies of the genital tract.¹ Extrauterine ESS (EUESSs) are those tumours that arise primarily from organs other than the uterus. EUESS can be classified into primary and secondary. Primary EUESSs occur without primary uterine involvement.² Secondary EUESS should then include all patients with other organ involvement who have had uterine ESS in the past. In patients who have had a prior hysterectomy, such classification (of EUESS) depends on the final histopathological report of the hysterectomy specimen. The principal issue in such patients is in defining whether the tumour is primary or secondary, particularly in those who have undergone a hysterectomy in the past.³

EUESS has been reported to occur in many organs. The common locations for EUESS include the ovaries, peritoneum, vagina, colon, anterior abdominal wall, small bowel, stomach, lung.⁴ Their extrauterine location, low incidence, non-specific symptoms and ability to mimic other pathologies present as a major diagnostic challenge in most cases.

EUESS involving the ureters is rare and only a very few cases are reported in the literature.⁵ The reported cases either presented with endometriosis or as a pelvic mass, infiltrating into the distal ureter. Isolated ureteral ESS, with intra-mural location, non-involvement of periureteric tissue and/or adjacent organ involvement has not been reported so far in the medical literature. Here, we report a rare case of a middle-aged woman who presented with loin pain and haematuria. On evaluation, she was diagnosed to have secondary ureteral EUESS, involving the distal ureter with resultant ureteral obstruction. There was no evidence of pelvic mass or pelvic organ involvement. To the best of our knowledge, ours is probably the first case to be ever reported of isolated ureteric involvement in secondary EUESS. The unusual presentation, features masking prompt diagnosis and diagnostic challenges faced are discussed here.

Case presentation

A 56-year-old woman presented with left loin pain and occasional painless haematuria for 1 month. She had undergone bilateral modified radical mastectomy for adenocarcinoma of the breast 10 years back and had completed a full course of adjuvant chemotherapy and radiotherapy. She also received adjuvant tamoxifen, 10 mg once a day, for 3 years. Eight years ago, she underwent radical hysterectomy for menorrhagia and the biopsy report was low-grade ESS. Physical examination of chest and abdomen were normal. There was no cervical or groin lymphadenopathy. Per-vaginal and digital rectal examinations were normal, with evidence of hysterectomy.

Investigations

On evaluation, her haemoglobin was 6.33 mmol/L. Her blood urea nitrogen and serum creatinine levels were within normal limits. The urine microscopy was normal and the urine culture was sterile. Ultrasound abdomen revealed a left hydroureteronephrosis with a 1.5 cm renal pelvic calculus. Figure 1A, B illustrates the coronal and cross-sections of CT of the abdomen showing a 1.3 cm left renal pelvic calculus. There was a left mild hydroureteronephrosis with dilatation extending up to the distal ureter.

Figure 1.

Unenhanced CT abdomen and ureteroscopic view of the bullous lesion in the distal ureter. CT abdomen showing the 1.3 cm left renal pelvic calculus; coronal view (A) and axial view (B). Ureteroscopic view of the circumferential solid polypoidal mass lesion obstructing ureteral lumen (C) and dilated proximal ureter with the guidewire in situ (D).

Differential diagnosis

The clinical diagnosis appeared straightforward. The cause of left loin pain was attributed to the renal calculus. The mild left ureteric dilatation was thought to be a residual dilatation of a passed out tiny ureteric calculus. However, at this stage (until a ureteroscopy was done), a few differential diagnoses were borne in mind, which included the following: distal ureteric stricture, radiolucent matrix stone and necrosed renal papilla. At no point in time (until confirmation with biopsy), ureteric ESS was ever considered as a possible diagnosis.

Treatment

Given her bothersome left loin pain, and as the cause of the pain was thought to be renal stone, a left percutaneous nephrolithotripsy (PCNL) was planned. However, because of left hydroureteronephrosis, an initial diagnostic left ureteroscopy was performed using a 6/7.5 Fr semi rigid ureteroscope, to ensure that none of the differential diagnoses gets missed out. Figure 1C, D illustrates the ureteroscopic view of the bullous polypoidal lesion and proximal dilated ureter with the guide wire in situ, respectively. The bullous lesion in the distal ureter occluding the lumen of the left ureter appeared like an inflammatory reaction that one gets at the site of ureteric impaction. Further negotiation of the scope beyond the lesion was abandoned because of the telescopic movement of the entire ureter. The rigid ureter raised suspicion of malignancy or extraneous compression, and hence, balloon dilatation of the obstructed segment was not attempted.

CT scan did not reveal any mass compressing or infiltrating into the ureteral lumen. Biopsy was taken from the ureteral mass and sent for both frozen section and conventional histopathological examination. As the frozen section report was inconclusive, the patient was turned prone and PCNL was completed. Though there were no changes in the ultimate outcome, performing PCNL in a patient with suspected ureteral malignancy was a cause of ethical concern. However, as the initial frozen section report was inconclusive, we decided to proceed with PCNL. Urine cytology from the ureteric catheter placed before PCNL showed atypical cells along with exfoliated metaplastic urothelial cells. However, this report was obtained only after the renal stone was removed and a double J stent placed. The final histopathology report demonstrated oval to spindle-shaped cells arranged in whorls and fascicles interspersed with thin-walled blood vessels. The cells showed strong receptor positivity for oestrogen and progesterone receptors (ER/PR). There was no evidence of increased mitosis or necrosis. In immunohistochemistry, tumour cells showed vimentin positivity but were negative for CD 10. Given the previous history of ESS and a strong ER/PR positivity, a diagnosis of low-grade EUESS was made. Since she had ESS of the uterus in the past, ours is a case of Secondary EUESS.

Considering a history of multiple malignancies in past, as histopathology reports were suggestive of low-grade EUESS, a whole-body Positron Emission Tomography (PET) Scan was done. Figure 2A illustrates the cross-sectional image of the kidney and figure 2B showing the distal ureter with DJ stent in situ. Figure 2C represents the whole body PET CT image, showing no evidence of distant metastasis. The PET CT did not show any evidence of extraneous compression of the distal ureter or any distant metastasis. Left laparoscopic radical nephroureterectomy and distal ureterectomy with a cuff of bladder excision (open technique) were performed.

Figure 2.

Whole-body PET-CT scan illustrating the kidneys, distal ureter and whole-body scan. Cross-section of the kidneys showing left renal calculus (A) and that of distal ureter showing the stent in situ with no mass encasing or exerting pressure effect over the distal ureter (B). Whole-body 18-Fluoro Deoxy Glucose Positron Emission Tomography (18-FDG PET CT) scan (2C) showing no regional or distant metabolic activity anywhere in the body.

Histopathology revealed a 2 cm lesion in the distal ureter and was diagnosed as low-grade ESS with no lymphovascular invasion. Figure 3A (×200 magnification) and figure 3B (×400 magnification) illustrate the H&E stain microphotographs of the distal ureteric mass where uniform sheets of oval to spindle-shaped tumour cells with prominent vessels and extravasated red blood cells are seen. Immunohistochemistry showed tumour cells with vimentin positivity and diffuse strong nuclear positivity for ER and PR. Figure 3C, D illustrates the immunohistochemistry microphotographs, depicting the ER and PR positivity, respectively. The biopsy of the nephrectomy specimen showed evidence of chronic pyelonephritis and acute interstitial nephritis. The postoperative period was uneventful. The patient was started on oral medroxyprogesterone for 8 weeks.

Figure 3.

H&E and immunohistochemistry (IHC) sections of the excised distal ureter showing EUESS. (A) (H&E, ×200 magnification) showing uniform sheets of oval to spindle tumour cells and intervening capillaries (white arrow) and (B) (H&E, ×400 magnification) showing prominent vessels with extravasated red blood cells (yellow arrow). (C, D) are the IHC images illustrating ER (×100 magnification) and PR (×200 magnification) positivity. ER, oestrogen receptor; EUESS, extrauterine endometrial stromal sarcomas; PR, progesterone receptor.

Outcome and follow-up

She is on regular follow-up for 1 year, without any complaints. There were no local or distant recurrences. She completed the full course of hormonal therapy and is advised to undergo a Positron Emisson Tomography (PET) CT scan after 1 year.

Discussion

ESS is part of a complex group of mesenchymal uterine neoplasms, representing 1% of all uterine malignancies.⁶ It is the second most common mesenchymal neoplasm involving the uterus, following leiomyosarcoma. Endometriosis is often recognised as the most common offending agent.⁷ Most of the EUESSs arise from endometriosis and turn malignant over some time.⁸ However, endometriosis needs not to be present in all patients with EUESS.⁹

EUESSs were classified as primary and secondary depending on whether the uterus is affected with ESS or not. Most literature mentions only primary EUESS. Secondary EUESS appears self-explanatory. EUESSs involving the urinary tract are relatively uncommon. In one of the largest series of ESS involving 63 cases, Masand et al observed ovary, bowel and peritoneum as the common organs affected.¹⁰ Tian et al reported six cases describing the urinary bladder as the primarily involved organ.¹¹ Ureteric involvement by EUESS is rare. Most published reports are on the infiltration of the ureteric wall from an external source. Cruz Guerra et al report a case of a 64-year-old woman who had undergone abdominal hysterectomy for ESS 30 years before, presenting with pelvic endometriosis infiltrating into the ureter.¹² Mercier et al reported a similar case of ureteral involvement, following ureteric reimplantation.¹³ Our patient, though similar to Mercier’s report, is unique because the disease was primarily located within the ureteric lumen, localised to the ureteral wall with non-involvement of the periureteric tissue. This is probably the first-ever case of secondary ureteral EUESS to be reported in the literature, arising de novo from within the ureteral lumen. Table 1 compares our study with similar earlier published studies of secondary EUESS affecting the urinary tract.

Table 1.

Comparison with other studies showing secondary EUESS with urinary tract involvement

Authors	Type of study	No of cases	Organ affected
Masand et al10	Original article	63	2 cases of urinary bladder
Tian et al11	Original article	6	All 6 involving urinary bladder
Cruz Guerra et al12	Case report	1	Secondary EUESS, pelvic endometriosis infiltrating into the ureter
Mercier et al13	Case report	1	Ureteral involvement, following left ureteric reimplantation, without pelvic endometriosis
Our study	Case report	1	Isolated Ureteral involvement arising de novo, without previous ureteric surgeries or pelvic endometriosis

EUESS, extrauterine endometrial stromal sarcomas.

Our case is probably the first ever to report an isolated secondary EUESS of the ureter arising de novo within the ureteral wall, without prior ureteric surgeries, extrinsic compression or pelvic endometriosis. Various risk factors may contribute to the development of EUESS. Patients on tamoxifen use, oestrogen therapy or those with a history of previous pelvic radiation or breast or ovarian cancer are additional predisposing factors for the development of EUESS.^{14 15} It needs to be emphasised that our patient had ingested tablet tamoxifen for three long years.

Surgical excision of EUESS is the recommended treatment in most patients. Adjuvant treatment with chemotherapy or radiotherapy is controversial and there are still no definite guidelines on the actual therapeutic efficacy of adjuvant treatment.¹⁶ The rarity of such tumours makes formulating evidence-based guidelines more difficult. As EUESS has a tendency to metastasise extensively and as adjuvant therapy is not shown to give a survival advantage, cytoreductive surgery is still recommended in most patients.¹⁷ Because of a dearth of literature evidence, most of the treatment for EUESS follows that of uterine ESS.¹⁸

Hormone receptor status further aids in prognosticating these tumours. Low-grade ESS tends to be ER and PR-positive in the majority of cases. Hormone therapy in such cases greatly helps lower the recurrence.¹⁹ In most of the low-grade ESS, oestrogen therapy is found to be effective.^{20 21} The benefits of hormonal therapy remains debatable, particularly in advanced and metastatic disease.

The effectiveness of adjuvant therapy is only 5%–27%. Survival further reduces recurrences after first-line treatment.²² Patients who are not fit for surgery, patients with comorbidities carrying a higher risk of surgical intervention and patients with high tumour burden are better treated with a combination of systemic therapy, hormonal therapy, palliative external beam therapy or brachytherapy.²³

Ureteric EUESS often poses a diagnostic dilemma. Because of its rarity, patients with non-specific symptoms are often misdiagnosed. CT scan might show evidence of hydroureteronephrosis, but needs a high index of clinical suspicion to make a prompt diagnosis. A biopsy is often needed from such suspicious lesions to make an accurate diagnosis. A tissue sample may often be limited in lesions involving the ureter. In such cases, hormone receptor positivity and immunohistochemistry may offer additional value. Molecular studies may offer invaluable information in such a setting. As ESS harbour chromosomal translocations, identification of gene fusions and gene translocations may be the future in the management of such cases. Conklin observed the JAZF1-SUZ12 translocation to be more specific and the most common genetic abnormality seen in most patients with ESS.²⁴ This translocation is not observed in other uterine mesenchymal neoplasms.²⁵

EUESS is a slow-growing tumour. Long, regular visits are an integral part of management to prevent recurrences. As most cases of ESS are missed out during initial evaluation, our report highlights the need for keeping EUESS on the list of differential diagnosis for lower abdominal and urinary tract tumours. The highlight of our case report is that ours is the first ever to report an isolated EUESS arising de novo from within the ureteral lumen, with no evidence of endometriosis or periureteral/adjacent organ involvement.

Patient’s perspective.

I consulted the doctor when I had loin pain in recent times. During the consultation, the doctor asked me about my personal life, relationship with my husband and kids. After examination, Iunderwent blood and urine examinations. After doing an ultrasound scan of my abdomen, the doctor told me that there is a stone in my left kidney. So he advised me to undergo a CT abdomen followed by asking me to undergo a key-hole operation for stone removal. The hospital stay was smooth and I underwent an operation the next day morning. After recovering from anaesthesia, my husband met me first and in front ofhim, my team of doctors explained that they had taken a biopsy from the left ureter which was the cause for the dilatation. After reviewing the biopsy report doctor advise me to undergo another operation which included the removal of my left kidney. Our team of doctors explained to us about my condition, possible causes, complications, similar cases in the world, prognosis and future implications. I recovered well after the operation and was discharged after 3 days of hospital stay. After reviewing the biopsy report doctor advise me to follow up with the department of oncology for hormone treatment.

I consider this whole experience a bit shocking. With a past similar experience and with the good support of my husband and the doctors who helped me with adequate counselling and good post-operative care, I now have learnt to overcome this problem and move on in life. Cheers!!

Learning points.

• Isolated ureteric extrauterine endometrial stromal sarcomas (EUESS) without endometriosis, arising de novo within the ureteral lumen, is extremely rare. Though being reported for the first time in literature, it is prudent for treating physicians to keep in mind, this rare possible entity.

• Immunohistochemistry using oestrogen receptor/progesterone receptor positivity greatly aids in the diagnosis of EUESS.

• Cytoreductive surgery is the definite treatment for EUESS. Need definite guidelines to substantiate the role of adjuvant chemotherapy or radiotherapy.

• Long and regular follow-up of EUESS is needed to prevent recurrences.

Ethics statements

Patient consent for publication

Obtained.