Surgical management of a congenital genital tract abnormality in a patient with Lynch syndrome

Abstract

Lynch syndrome (LS), also known as hereditary non-polyposis colorectal cancer, is an inherited cancer syndrome which increases the risk of developing colorectal cancer and endometrial cancer. Individuals with LS have an increased risk of cancers of the ovary, urinary tract, stomach, small intestine, pancreas, biliary tract, brain and skin. Cancer risk reduction is recommended through chemoprevention (aspirin), surveillance (colonoscopy, assessment of the endometrium and ovaries via USS, aspiration biopsy and tumour marker monitoring; CA125) or risk reduction surgery, that is, total hysterectomy and bilateral salpingo-oophorectomy.

This is a case of a nulliparous woman in her early 30s with LS and a congenital genital tract malformation. She had a unicornuate (left) uterus and a vestigial (right) uterine horn. There was an inability to obtain a conclusive set of endometrial biopsies in this patient due to the nature of the patient’s congenital uterine abnormality. In this case, surgery was recommended to excise the vestigial horn and fallopian tube in order to optimise surveillance and fertility.

Background

Lynch syndrome (LS) is an autosomal dominant genetic syndrome associated with an increased incidence of cancer in affected families. The lifetime risk of colorectal, endometrial and ovarian cancers increases to up to 70%, 60% and 12%, respectively.^{1 2}

In this case, when considering the age of the patient, fertility preservation was an important factor when evaluating the various risk-reducing options.

Case presentation

She initially presented to the gynaecology daycase unit with a 2-day history of suprapubic pain and dysuria, a symptom which was worse during defecation.

Her medical history includes LS (MSH2 mutation) and irritable bowel syndrome. She has a strong family history of cancers associated with LS, which includes endometrial and colorectal cancers, both of which affected first-degree relatives.

She had a negative pregnancy test and positive urine analysis, suggesting a urinary tract infection (UTI).

On speculum examination, white discharge was noted. A transvaginal ultrasound scan (USS) of the pelvis showed a 2.3×3.1 cm heterogenous mass anterior to the right ovary. She was discharged home on oral antibiotics for a UTI.

She re-presented with persistent right iliac fossa pain 10 days later, although her urinary symptoms had resolved. At this point, further investigations were performed, which included cancer antigen 125 (CA-125, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and a repeat pelvic USS. All tumour markers returned within the normal range. Her repeat USS showed findings consistent with that of the initial scan.

Given the patient’s medical history of LS and the USS findings, an MRI scan of the pelvis was arranged to further assess the suspected adnexal mass. The MRI scan showed an adnexal cystic lesion adjacent to the right fallopian tube, which was of uncertain clinical significance and a left involuting corpus luteum.

Following the MRI findings, her case was referred to the local gynaecology multidisciplinary team (MDT) meeting. Based on the MDT outcome, the patient was subsequently offered two management options: to either take a more conservative approach which involved monitoring with serial imaging or, conversely, a more proactive approach with a diagnostic laparoscopy and biopsy of the right adnexal lesion. Based on her medical history of LS, she decided she would take a more proactive approach to management, choosing the diagnostic laparoscopy.

Investigations

Diagnostic laparoscopy revealed a unicornuate left uterus with a non-communicating right rudimentary horn (class IIB) and endometriotic deposits within the pelvis (figure 1). Endometriotic deposits were most likely secondary to retrograde menstruation from the horn into the pelvis, a feature that was likely contributing towards the patient’s presenting symptoms in this case.

Figure 1.

Laparoscopic image lt unicornuate uterus and rt rudimentary horn. lt, left; rt, right.

An endometrial biopsy from the left unicornuate uterus was obtained during the laparoscopy. However, as the right rudimentary horn of the uterus was blind ending, biopsy samples could not be taken. The endometrial biopsy samples taken from the unicornuate uterus showed no evidence of malignancy on histological assessment.

A review of the MRI scan (figure 2) following the diagnostic laparoscopy demonstrated that the signal within the previously described ‘right adnexal mass’ was equivalent to the signal within the endometrium of the unicornuate uterus. This provided satisfactory clinicoradiological correlation.

Figure 2.

MRI scan showing right adnexal mass.

Treatment

Following discussion of the laparoscopic findings with both the MDT and the patient, the patient was listed for risk reduction surgery. She had a laparoscopic excision of the right rudimentary horn of the uterus with right salpingectomy (figure 3). The right ovary was left in situ. The peritoneum with the endometriotic deposits in the right ovarian fossa was excised. An endometrial biopsy was obtained from the left unicornuate uterus, with excised samples sent for histological analysis.

Figure 3.

Excised rudimentary horn and fallopian tube. rt, right.

The histology report confirmed the clinical diagnosis of a right rudimentary uterine horn. The endometrial biopsy from the left unicornuate uterus demonstrated the presence of late secretory-phase endometrial tissue. The right fallopian tube showed hydrosalpinx. The endometrium of the right rudimentary horn was found to be late secretory-phase endometrium. Within the surrounding myometrium, there was a foci of adenomyosis. Peritoneum from the right ovarian fossa showed mild inflammatory changes. In summary, there was no evidence of atypia or malignancy.

The adenomyosis and peritoneal inflammatory changes secondary to the retrograde menstruation from the right rudimentary uterine horn was most likely the cause of the patient’s pelvic pain.

Outcome and follow-up

The patient’s care will continue with ongoing surveillance under the care of a gynaecological hereditary cancer specialist. The patient will be offered risk-reducing surgery in the future once she feels she has completed her family or is alternatively beyond a childbearing age.

Discussion

LS occurs as a result of inherited mutations in the DNA mismatch repair (MMR) genes. Associated genes include MLH1, MSH2, MSH6, PMS2 and the EPCAM gene. In this patient’s case, she was diagnosed with an MSH2 mutation.

Uterine congenital anomalies are most commonly caused by the incomplete fusion of the Müllerian ducts during embryonic development. There is a poor understanding of the cause of malformation during this developmental process. In addition, the role that genetics plays in uterine congenital abnormalities is still unclear.

Kwiatkowski et al explored the association between the development of congenital malformations and hereditary mutations which increase the risk of cancer, mainly BRCA and MMR mutations.³

The study concluded that both BRCA and MMR mutations significantly increase the risk of congenital uterine malformations.³

This confirmed the hypothesis from an earlier study that the malformations seen were the result of faulty or inefficient DNA repair functions within the genes.⁴

In this case, the excision of the rudimentary horn served as a risk reduction surgery as well as treatment of the symptoms secondary to adenomyosis, endometriosis and retrograde menstruation from the right rudimentary horn into the pelvis.

Infertility is well known to be associated with endometriosis; between 30% and 50% of women with endometriosis have trouble conceiving.⁵ Although there are multiple theories on the mechanism of action, there is yet to be a widely accepted explanation.

Several studies have highlighted improved fertility outcomes following surgical management in patients with stage I–IV endometriosis.⁶

The excision of the rudimentary horn also improves the patient’s fertility outcomes in the future while reducing the risks of complication during pregnancy. The main risk in this case is that of hematometra in the rudimentary uterus, which could lead to further obstetric complications.

Learning points.

• This is a case of a patient with Lynch syndrome (LS) and a congenital uterine abnormality. The presence of the former informed the management strategy for the later.

• The treatment strategy in this uncommon case was guided by input from a multidisciplinary team and the patient’s ideas, concerns and expectation.

• Congenital anomalies in patients with LS pose challenges with cancer surveillance. Hence, it is crucial that the surveillance pathway should include clear recommendations for these patients.

• This case highlights the need for further research into the possible link between hereditary mutations and congenital anomalies.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).