A rare case report of low-grade endometrial sarcoma: A surgical tale from Himalayas

Abstract

Introduction

In the context of female genital tract malignancy, uterine sarcoma is considered the rarest form of the disease. Despite the inert nature of low-grade endometrial sarcoma, they must be meticulously diagnosed on time, with an exact grading of the severity and staging of the disease, which further guides the treatment modality and prognosis.

Case summary

A married Asian female without any significant past medical and surgical history complained of abdominal distension and discomfort, which was progressive in nature, for which a radiological assessment was made that showed features suggestive of endometrial sarcoma. Total abdominal hysterectomy with sapingoopherectomy was done without any perioperative complications. Histology further confirmed the diagnosis. Post-operatively, the patient had an unremarkable hospital stay and was discharged home.

Discussion

Endometrial stromal sarcoma is one of the rare malignant entities presenting usually in late adult females, but sometimes it can present at an earlier age as well. Abdominal masses in females, although usually overlooked as benign, can sometimes be associated with a malignant picture. Low-grade endometrial sarcomas have been seen to masquerade other minor benign cases, such as leiomyoma. Despite the rarity of such malignant conditions, diagnosis and management are rather straightforward, and post-operative patient prognosis has been found to be rewarding.

Conclusion

Among the uterine sarcoma cases, endometrial sarcoma comes under the malignant disease of the least occurrence. Compared to other malignant conditions, these patients present with minor symptoms like discomfort, which may go unchecked. The major factor that should be noted is the on-time diagnosis and appropriate choice of treatment modality. Overall, despite a minute prevalence and difficult diagnosis, the prognosis of the patient is rather good.

Highlights

• •Endometrial stromal sarcoma (ESS) is a rare and challenging condition that usually affects women in their late 40s and 50s.
• •Low-grade Endometrial stromal sarcoma is an underrated differential diagnosis in the presentation of abdominal mass.
• •Ultrasound lacks specificity for ESS and can suggest an incorrect diagnosis of more prevalent conditions such as adenomyosis or, in our case — an ovarian cyst.
• •Total abdominal hysterectomy with bilateral salpingo-oophorectomy is recommended for LG-ESS treatment.
• •Timely diagnosis and prompt surgical intervention can halt the disease progression, thereby achieving the best prognosis.

1. Introduction

Uterine sarcomas are rare encounters among the tumors of the female genital tract that account for approximately 1 % of all female genital tract malignancies and 3–7 % of uterine cancers [1]. They may arise from connective tissue, smooth muscle or endometrial stroma and are histologically classified into leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS) and undifferentiated uterine sarcoma (UUS) [2]. The endometrial stromal sarcoma variant is an even rarer occurrence, constituting approximately 10 % of all uterine sarcomas with an annual incidence of 1–2 per million women [3]. Based on histopathological, immunohistochemical and molecular features, WHO has classified endometrial stromal sarcoma into four grades: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS) [4]. The histological grading directly correlates with the prognosis; high-grade ones are generally aggressive, and low-grade ones have an inert nature. ESS has been staged from I to IV by the International Federation of Gynecology and Obstetrics (FIGO). While postmenopausal women are usually prone to uterine sarcomas, the LG-ESS variant has a slightly younger age predilection, targeting a median age of 50 years [5]. The diagnosis is challenging because clinical examination and imaging findings are usually inconclusive, and a histopathological examination is almost always required to provide a definitive diagnosis. Surgical management by Total Abdominal hysterectomy and Bilateral Salpingo-oophorectomy is the standard recommendation for LGESS, and the patient is planned for routine long-term follow-up and adjuvant therapy since it has a very high recurrence rate [6]. This case report have been written in accordance with SCARE guideline [7].

2. Case summary

We present a case of 38 years old Asian female who presented to the outpatient department of gynecology and obstetrics with the complaint of pain abdomen for six months, increasing in intensity since the last 3 months, the pain was continuous in nature, with a burning sensation aggravated on activities and relieved during rest. She gave a history of dysmenorrhea for three months, onset of pain D1 till D3 of menstruation relieved on medication. The patient noticed a mass per abdomen for three months, which increased in size over a period of 3 months. There was no history of PV discharge, fever, loss of appetite, or weight loss. Bowel and bladder habits were normal. No history of Diabetes mellitus, hypertension, thyroid disorder, tuberculosis, genital tract malignancies, or any other chronic illness in the past. No history of medication for any chronic illness. As per her obstetrics history she was married for 15 years with the first child (female) born 14 years back via normal delivery at home, and the second child (female) was born 11 years back via normal delivery at home and no significant antenatal, natal and post natal history Her menstrual history did not suggest any abnormalities, and she had regular cycles; the length of the cycle being 28 ± 5 days, the duration of flow was 3–4 days, and she used 2–3 pads/day, which were partially soaked, no history of passage of clots, dysmenorrhea was present but was relieved on medication. There is no history of intermenstrual bleeding or post-coital bleeding. Her past medical and surgical history were uneventful. During her presentation to our outpatient department, her general condition was fair, well-built, and nourished, with a BMI of 20.4 kg/m², her vitals were stable, and there were no significant findings in the respiratory, cardiovascular and neurological examination. On her per-abdominal examination, on inspection, the umbilicus was central and inverted, all quadrants were moving equally with respiration, there were no scars, sinuses, dilated veins, or visible pulsation, and hernial orifices were intact. On palpation, there was no local rise in temperature, the abdomen was non-tender, and there was an ill-defined mass palpable below the level of umbilicus in the midline, the size of which corresponded to an 18-week gravid uterus. The mass had a firm consistency with an irregular outline. The upper border was smooth and well-defined, and the lower border was not palpable. The mass had restricted mobility. On percussion, a dull note was felt over the mass. On performing a bimanual pelvic Examination, the uterus could not be felt separate from the mass, and the mass was felt high up in the pouch of Douglas.

An ultrasound scan of the pelvis showed a normal-sized uterus with an endometrial thickness of 4 mm and a cystic lesion measuring approx. 117 × 103 × 105 mm with septations noted in the POD region over the posterior fundus. The ovaries and adnexa appeared normal, and there was no free fluid in POD. A provisional diagnosis of ovarian cyst under query was made because of the impression of a large cystic lesion with septation noted in the pouch of Douglas region. Tumor markers were within normal range CEA: 2.2 ng/ml (<5) CA-125: 23.8 (35 U/ml) Beta hCG: 1.39 Alpha fetoprotein: 1.14 (<10).CT scan of abdomen showed An oval well defined cystic lesion measuring about 10.3 × 11.8 × 10.7 cm in mid abdominopelvic region. It has thickened regular enhancing wall (6.1 mm). No evidence of internal enhancement of mentioned lesion on contrast study (Fig. 1). It is abutting right side of uterus with poor adjacent fat plane at places and compressing urinary bladder inferiorly with maintained adjacent fat plane. No evidence of fat attenuation/solid component/calcification B/L ovaries not separately visible Suggestive of ovarian lesion — likely benign. Total abdominal hysterectomy (Fig. 2) with right salpingectomy with left sapingoopherectomy was done with no intraoperative or postoperative complications. No pelvic lymph node metastasis and extension was observed during intraoperative period. Operative findings revealed a uterus approximately correlating to an 18-week gravid uterus size and had a smooth outline. The right tube and ovary were normal, and the left tube was normal; the left ovary was adherent to the posterior surface of the uterus. On the cut-section of the uterus, the whole endometrial cavity was occupied by a cystic mass (10 × 10 cm) containing straw-colored mucinous/serous fluid around 500 ml (Fig. 3). The wall of the cyst was rough. The endocervical canal was normal. Post-operatively, a histopathological examination and immunohistochemistry were performed, which confirmed the diagnosis of LG-ESS with characteristics suggestive of myometrium. The specimen was positive for malignancy, Morphological features s/p endometrial stromal sarcoma, LESS, the tumor was limited to the uterine fundus and corpus with a tumor size of 9 cm. The lymphovascular invasion was focal, and the peritoneal/ascitic fluid was negative for malignancy. The tumor was classified as TNM: T1b Nx Mx and FIGO stage (2015): IB. Other details included the endometrium in the secretory phase, and bilateral fallopian tubes were unremarkable. In the left ovary, cystic follicles were also noted. Hence, according to the new 2009 FIGO Staging, it was stage IB disease of low-grade endometrial stromal sarcoma. Furthermore, the postoperative period was uneventful, and the patient was discharged after five days with a prescription of antibiotics, Iron tablets, and vitamin C. Patient was followed up for the initial few months, and there were no new complaints. The patient was symptomatically better, and the patient was further suggested for additional care by the Department of Oncology. Later there was not any need for chemotherapy as well.

Fig. 1.

CT abdomen and pelvis showing an oval well defined cystic lesion measuring about 10.3 × 11.8 × 10.7 cm in mid abdomino-pelvic region. It has thickened regular enhancing wall (6.1 mm). No evidence of internal enhancement of mentioned lesion on contrast study. It is abutting right side of uterus with poor adjacent fat plane at places and compressing urinary bladder inferiorly with maintained adjacent fat plane. No evidence of fat attenuation/solid component/calcification B/L ovaries not separately visible suggestive of ovarian lesion.

Fig. 2.

Total abdominal hysterectomy with right salpingectomy with left sapingoopherectomy was done. Operative findings revealed grossly a uterus 18-weeks size with a smooth outline, right tubes and ovary were normal. The left tube was normal and left ovary was adherent to posterior surface of uterus.

Fig. 3.

On cut section the whole endometrial cavity was occupied by a cystic lesion with a straw colored mucinous/serous fluid (500 ml).

3. Discussion

Endometrial stromal sarcoma (ESS) is a rare and challenging condition that usually affects women in their late 40s and 50s. Our patient had an unusually early disease presentation at the age of 38 years. Uterine sarcoma contradicts the usual trend of most gynecological tumors getting discovered at an early stage with the help of routine checkups, as these are usually asymptomatic and clinically mimic a common benign uterine tumor, leiomyoma. The most common clinical presentation of ESS is abnormal uterine bleeding (45 %) was the most common clinical presentation, followed by palpable mass (20 %), and rapid growth of leiomyoma (10 %). 1/4th of the patient can be asymptomatic [8]. Clinically, a uterine mass may be assessed based on its size, contour, and mobility of the uterus with adnexas. A fixed mass is more suggestive of a malignant neoplasm than a mobile mass. However, this is not pathognomonic since a malignant neoplasm with no uterine serosal invasion may be mobile, and a mass associated with endometriosis or pelvic infection may be fixed. Unfortunately, no examination findings can distinguish a leiomyoma from a uterine sarcoma. The index case also presented with a history of dysmenorrhea, abdominal pain and a palpable abdominal mass. Although ESS runs an indolent course, extrauterine involvement, notably on the ovaries, rectal wall, peritoneum, and vagina, has been found in up to 30 % of women posing a diagnostic challenge due to site-specific varied presentation [3].

A study conducted by Masand et al. reported associated endometriosis in approximately 60 % of their cases [9]. In cases where endometriosis was not identified, it might have evolved from gland-poor endometriosis, overgrowth of tumor obscured the underlying endometriosis, or it may arise de novo from the coelomic epithelium. A history of endometriosis was not available in our case at the time of diagnosis.

Ultrasound lacks specificity and can suggest an incorrect diagnosis of more prevalent conditions such as adenomyosis or leiomyoma, or, in our case — an ovarian cyst. MRI may be helpful in women with ESS; however, it does not provide a definitive diagnosis. Uterine curettage is an important method of preoperative diagnosis of ESS because despite the bulk of the tumor always being intramyometrial, most of these sarcomas involve the endometrium as well. However, the sensitivity of uterine curettage is compromised in cases where the lesion is completely within the myometrium [3]. The definitive diagnosis thus depends upon the histological examination done postoperatively. Morphologically, LG-ESS usually displays a multinodular growth, with poorly defined tan to yellow soft nodules within the myometrium and endometrium, but in some cases, it can look identical to endometrial stromal nodules (ESN) with a deceptively well-circumscribed appearance. Thus, the histopathological distinction of these two pathologies is important where the latter still retains the well-circumscribed nature histologically. It may occasionally present with infiltrative margins; however, these should be 3 mm or less in maximum dimension and not exceed three foci. LG-ESS usually appears infiltrative histologically, with a tongue-like margin formed from cells closely resembling those of endometrial stroma in the proliferative phase and lymphovascular invasion (LVIS). An important point of note is that the biopsy of the specimen cannot make a diagnosis of LG-ESS with certainty as the margins of the tumor cannot be assessed properly, and thus, a hysterectomy specimen is preferred. [10] Immunohistochemistry can be very useful in the diagnosis of LG-ESS. While ESS, leiomyoma, and LMS may be expressed in ESS, leiomyosarcoma, and leiomyoma, a valuable marker for ESS is diffuse CD-10 reactivity, a marker which can also differentiate LG-ESS from HG-ESS [11].

Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the recommended surgery for LG-ESS treatment [12]. Complete resection of disease without fragmentation and with negative surgical margins should be the end target of the surgery. In cases of young women, ovary-sparing surgery can be considered depending on tumor hormonal receptor status, and myomectomy should be considered only for young patients with a strong desire for fertility, with fully informed consent and a planned hysterectomy after the completion of pregnancy [13]. However, this recommendation has conflicting findings, with Lissoni et al. reporting successful pregnancy without recurrence in 50 % of the patients [14], and Koskas et al., in their case study, finding a shorter than usual recurrence of the tumor after pregnancy [15]. Despite having a low malignant potential and an indolent course, they are well known for their late recurrences even in patients with stage I disease. LGESS has a relatively high recurrence rate, at about 60 %, and the disease-related death rate is estimated to be between 15 % and 25 % [16]. With the high likelihood of recurrence, clinicians confidently recommend the use of adjuvant chemotherapy, radiation therapy, and/or hormone therapy to suppress tumor growth, even in cases of localized tumors effectively. However, these recommendations for adjuvant chemotherapy and radiotherapy have been drawn based only on evidence from retrospective study designs [17]. Hormone therapy with progestins, tamoxifen, gonadotropin-releasing hormone (GnRH) analogs, and aromatase inhibitors are suggested for LGESS stages 3–4 and for recurrent disease [18]. Patients should also be planned for a routine follow-up on a long-term basis. Despite the high rates of recurrence, the overall prognosis is quite favorable. While primary LGESS patients have 5-year disease free survival and overall survival rates of over 90 % 5-year, patients with LGESS recurrence have higher recurrence and mortality rates, and the survival rate for stages III–IV is 50 % [19,20]. Currently, there are several pros and cons to each of the methods used for identification of uterine sarcoma preoperatively. Elevated serum markers CA-125, LDH, CRP, and D-dimer may points towards uterine sarcoma, but are susceptible to other factors and lack specificity. Compared to other modalities ultrasound is affordable and convenient, and is considered the best method of screening, but does not well identify whether the uterine masses are benign or malignant. Although MRI has good soft tissue resolution, there is a certain rate of misdiagnosis because certain degenerative types of uterine fibroids have similar signal intensities. PET-CT is considered diagnostic modality with the highest accuracy but is expensive and difficult to access in middle income countries. Preoperative biopsy pathology is the gold standard for diagnosis, but requires a high level of physician skill and has the potential for inadequate sampling and missed examinations. Clinical manifestations such as rapidly growing tumors and elevated serum markers in patients, abnormalities in imaging examinations can alert clinicians to avoid crushing masses of unknown. Preoperative puncture biopsy with its long term results are also under observation for potential diagnostic modality with high accuracy [21].

4. Conclusion

Among the cases that presents as abdominal mass, low grade endometrial sarcoma is one of the differential diagnosis that comes into the context rarely due to its significantly minimal prevalence. Timely diagnosis and prompt surgical intervention can halt the disease progression hence bringing about the best prognosis and further helps to avoid multi system involvement.

Sources of funding

None.

Ethical approval

It is exempted at our institutions. We don't need to get approval from the ethical committee for the case report.

Registration of research studies

Not a first in man study.

Consent

Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

Conceptualization: Sagun Ghimire.

Writing original draft: Sagun Ghimire, Pratima Shrestha, and Kritick Bhandari.

All authors were involved in reviewing, editing, supervising, and preparing the final manuscript.

Guarantor: Sagun Ghimire.

Declaration of competing interest

None.