Delayed diagnosis of Herlyn-Werner-Wunderlich syndrome with diffuse adenomyosis in bilateral horns

We present you a case of 43 years nulliparous female who presented in our tertiary care hospital with dysmenorrhea and irregular menstrual bleeding since few years after her menarche. As she was unmarried and not desiring for fertility, history of infertility or pregnancy loss was neither relevant nor of concern in our case. Previously, on gynecological visit and Ultrasound scan, she was incorrectly diagnosed with subserosal uterine fibroid and was only being treated for pain with NSAIDS and counselled for myomectomy/hysterectomy. However absence of left kidney in left renal fossa and other ectopic sites on ultrasound scan was suggestive of left renal agenesis. Due to persistent symptoms, this time she came to our health care center seeking further treatment. Per abdomen examination was normal. Visual inspection of genital areas did not show any abnormality. Routine blood investigations along with hormonal profile and thyroid function tests which were within normal limits.

Ultrasound (Abdomen and Pelvis) showed 2 separate divergent uterine horns with wide fundal cleft. Two separate cervices were seen. Ill-defined hypo echoic collection was noted in left cervix suggesting some obstruction distally, however no definite obstructing lesion was noted ( Fig. 1 ). Endometrial cavities were separate with no communication between them. Bilateral uterine horns were enlarged with multiple subendometriotic and myometrial cysts and indistinct junctional zone ( Fig. 2 ). There was absence of left kidney in left renal fossa along with other possible ectopic sites suggestive of left renal agenesis ( Fig. 3 ). Fig. 1 Two separate divergent uterine horns with wide fundal cleft and 2 separate cervices (right-bold white arrow and left –open white arrow) with collection in left cervical canal (thin white arrow). Fig 1 Fig. 2 Enlarged bilateral uterine horns with heterogeneous echotexture (right- open white arrow, left- block white arrow) and multiple subendometriotic and myometrial cysts (thin white arrows) and indistinct junctional zone. Fig 2 Fig. 3 Normal right kidney (block white arrow) with empty left renal fossa (open white arrow). Fig 3 Two separate divergent uterine horns with wide fundal cleft and 2 separate cervices (right-bold white arrow and left –open white arrow) with collection in left cervical canal (thin white arrow). Enlarged bilateral uterine horns with heterogeneous echotexture (right- open white arrow, left- block white arrow) and multiple subendometriotic and myometrial cysts (thin white arrows) and indistinct junctional zone. Normal right kidney (block white arrow) with empty left renal fossa (open white arrow). This triad of 2 separate uterus and cervix, left sided hematocolpos and left renal agenesis clinched the diagnosis of Herlyn-Werner-Wunderlich -Syndrome with features suggestive of adenomyosis in bilateral horns. However, definite vaginal septum was not visualized. So for further classifying the subtypes as well as for definitive diagnosis of adenomyosis, patient's was advised for MRI pelvis. MRI pelvis showed- Two separate uterus with widely divergent apices, 2 separate cervices and vagina ( Fig. 4 ). Vaginal canal of right uterine horn was patent whereas there as a linear hypointense band obliterating the left vaginal canal (likely septum) with collection in left cervical canal measuring approximately 6 mL showing T1/T2 SPAIR high signal intensity (s/o hematocolpos) ( Fig 5 ). There was no communication between the cervix on both sides. Fig. 4 T2 Sagittal and Coronal images showing 2 separate uterus (Right- bold white arrow, left- block white arrow) with widely divergent apices (bold blue arrow), 2 separate cervices (right-curved white arrow, left- curved block arrow) and vagina (right-thin white arrow, left- thin blue arrow) . Fig 4 Fig. 5 Sagittal T2 weighted image showing T2 hypo intense vaginal septum (Thin white arrow). T1/T2/SPIR axial images showing high signal intensity collection in left cervical canal suggestive of hematocolpos (bold white arrow) and normal right cervical canal (block white arrow). Fig 5 T2 Sagittal and Coronal images showing 2 separate uterus (Right- bold white arrow, left- block white arrow) with widely divergent apices (bold blue arrow), 2 separate cervices (right-curved white arrow, left- curved block arrow) and vagina (right-thin white arrow, left- thin blue arrow) . Sagittal T2 weighted image showing T2 hypo intense vaginal septum (Thin white arrow). T1/T2/SPIR axial images showing high signal intensity collection in left cervical canal suggestive of hematocolpos (bold white arrow) and normal right cervical canal (block white arrow). Both the uterine horns were enlarged with normal endometrium and loss of junctional zone. Asymmetrical thickening of myometrium was noted in bilateral uterine horn with multiple T1 low, T2/SPAIR high signal intensity foci(s/o cysts) in subendometriotic region and myometrium of both uterine horns. These findings were in favor of diffuse adenomyosis in bilateral uterine horns ( Fig. 6 ). Fig. 6 T2 axial image showing enlarged bislateral uterine horns with asymmetrical myometrial thickening (thin white arrows) with normal endometrium(thin blue arrows), loss of junctional zone(block white arrows) and multiple subendometriotic cysts (bold white arrows). Fig 6 T2 axial image showing enlarged bislateral uterine horns with asymmetrical myometrial thickening (thin white arrows) with normal endometrium(thin blue arrows), loss of junctional zone(block white arrows) and multiple subendometriotic cysts (bold white arrows). Coronal SPAIR image showed absence of left kidney in left renal fossa ( Fig. 7 ). Fig. 7 T2/SPAIR Coronal image showing absence of kidney in left renal fossa (thin white arrow). Fig 7 T2/SPAIR Coronal image showing absence of kidney in left renal fossa (thin white arrow). All these findings were in favor of Herlyn-Werner-Wunderlich –Syndrome Class Ia with adenomyosis. Following this, patient was counselled about her condition and treatment options. Patient was not desiring for fertility, so hysterectomy option was offered as a definitive treatment option along with vaginal septoplasty and medical treatment for adenomyosis as other option. However, patient was reluctant for hysterectomy and vaginal septoplasty was done to relieve hematocolopos as a cause of pain. And for adenomyosis she was kept on hormonal medications. Currently she is having regular menstrual periods and dysmennorhea has decreased as compared to before.

Informed consent has been obtained to include case details, personal information and images of the patient in publication.

HWWS is a very rare congenital anomaly of the genitourinary system characterized by uterus didelphys with blind hemivagina and ipsilateral renal agenesis more common on right side.. Our case differs from other case reports due to association with diffuse bilateral adenomyosis which is uncommon in this syndrome as obstruction is at the level of vagina. Also there was delayed diagnosis which was due to misdiagnosis rather than delayed symptoms. If there had been early diagnosis, patients could have lived pain free life these long years and also adenomyosis might have been prevented if it occurred secondary to this syndrome. Hence early and appropriate work-up should be done to prevent long term complications like infertility.

HWW syndrome is a rare congenital anomaly of the genitourinary system characterized by uterus didelphys with ipsilateral obstructed hemivagina and ipsilateral renal agenesis more common on right side [ 4 ]. Herlyn, Werner, and Wunderlich described this uterine anomaly associated with renal agenesis in the 1970s and hence the name was given [ 4 , 6 ]. It occurs secondary to mullerian duct abnormality [ 1 ]. Failure of development of mesonephric duct leads to renal agenesis which in turn influences development of the ipsilateral Mullerian duct [ 2 , 7 ]. Hence this anomaly is the result of failure of fusion of mullerian ducts and abnormal development of wolffian duct [ 7 ]. Uterus didelphys consists of 2 completely symmetric separate uterine cavities each with its own endometrial cavities and cervices [ 8 ]. About three-fourth of the cases present with complete or partial longitudinal vaginal septum [ 5 ]. Most of the cases present with renal agenesis and hematocolpos and/or hematometra due to obstruction by vaginal septum [ 8 ]. Detailed examination of urogenital system should be done when female genital anomaly is initially identified and vice versa [ 7 ]. Patient can also present with ectopic insertion of ureter and endometrioma [ 9 ]. There are 9 main types of uterine anomalies according to American Society for Reproductive Medicine (ASRM) [ 6 ]. Uterus didelphys belongs to class III among these 9 anomalies [ 10 ]. HWW syndrome usually presents after menarche with symptoms secondary to hematocolpos like cyclical dysmenorrhea but there can be delayed presentation if vaginal septum is incomplete [ 11 ]. Long term complications like endometriosis and infertility can occur if diagnosis or presentation is delayed [ 5 ]. Development of adenomyosis is less likely to occur in HHWS than in other syndromes as there is decreased risk of penetration of endometrial cells within myometrial layer because obstruction is at level of vagina which accommodates pressure of hematocolpos [ 12 ]. However, adenomyosis can also present as a primary lesion [ 13 . In our case too diffuse adenomyosis in bilateral horns was present. Ultrasound is cheap and noninvasive modality to diagnose uterine anomaly, hematocolpos and renal agenesis, however septum cannot be clearly delineated in contrary to MRI [ 3 ]. Magnetic resonance imaging (MRI) is the imaging modality of choice for the diagnosis and classification of MDA and also to diagnose associated pathologies such as endometriosis, pelvic inflammation and renal abnormalities [ 14 ]. Vaginal septoplasty is the treatment of choice for obstructed hemivagina with hematocolpos [ 2 , 14 ]. In complications like adenomyosis hormonal menstrual suppression is done initially and hysterectomy may be considered if symptoms are persistent and patient does not want to preserve fertility [ 15 ].

The Herlyn-Werner-Wunderlich syndrome is characterized by 3 entities like uterus didelphys, unilateral obstructed hemivagina and ipsilateral renal agenesis [ 1 ]. This syndrome was first described in 1922 in a young woman with symptoms of pelvic pain and a pelvic mass after menarche with regular menstruation [ 2 ]. It is also called OHVIRA [ 3 ]. It occurs due to mullerian duct abnormalities and usually presents at puberty with clinical features like dysmenorrhea and hematocolpos [ 4 ]. On USG uterine didelphys, hematocolpos and renal agenesis can be diagnosed, however evaluation of vaginal septum can be done better on MRI [ 3 ]. Presentation can be delayed if vaginal septum is incomplete [ 5 ]. It is more common on right side as compared to left [ 2 ]. Though various case reports are available on this syndrome, our case differs from others in view of its delayed diagnosis with associated diffuse adenomyosis in bilateral horns.