Primary low-grade extrauterine endometrial stromal sarcoma with sex cord elements involving the omentum: A case report with review of literature :Chikkanaganna P Manjula, V Suguna Beluru, B. K. Hanumantha Raju, Naina Mary Simon, Archives of Medicine and Health Sciences

CASE REPORT
Year : 2022 | Volume : 10 | Issue : 1 | Page : 87--90

Primary low-grade extrauterine endometrial stromal sarcoma with sex cord elements involving the omentum: A case report with review of literature

Chikkanaganna P Manjula¹, V Suguna Beluru², B. K. Hanumantha Raju³, Naina Mary Simon⁴,
¹ Department of Pathology, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka, India
² Department of Pathology, Saptagiri Institute of Medical Sciences, Bengaluru, Karnataka, India
³ Department of Urology, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka, India
⁴ Department of Pathology, Christian Medical College, Vellore, Tamil Nadu, India

Correspondence Address:
Dr. Chikkanaganna P Manjula
Department of Pathology, Kempegowda Institute of Medical Sciences, Banashankari 2^nd Stage, Bengaluru - 560 070, Karnataka
India

Abstract

Endometrial stromal sarcoma (ESS) is a rare mesenchymal neoplasm, accounting for 0.2% of all uterine malignancies. They also occur in extrauterine locations such as ovaries, rectal wall, pelvic peritoneum, and vagina, where it is associated with endometriosis. Here, we present a case of extrauterine ESS of the omentum, which resembled a urachal cyst on imaging studies. Intraoperatively, the bladder was normal, and multiple solid cystic nodules were noted in the omentum. Histopathological examination revealed features of spindle cell neoplasm. Immunohistochemistry helped in arriving at the final diagnosis of low-grade endometrial stromal sarcoma with sex cord-like elements. However, extensive sampling did not reveal endometriotic foci. Further investigations to search for a primary lesion in the female genital tract were futile, and patient remained asymptomatic 2 years after surgery. Like in uterine ESS, surgery remains the mainstay of treatment.

How to cite this article:
Manjula CP, Beluru V S, Raju BK, Simon NM. Primary low-grade extrauterine endometrial stromal sarcoma with sex cord elements involving the omentum: A case report with review of literature.Arch Med Health Sci 2022;10:87-90

How to cite this URL:
Manjula CP, Beluru V S, Raju BK, Simon NM. Primary low-grade extrauterine endometrial stromal sarcoma with sex cord elements involving the omentum: A case report with review of literature. Arch Med Health Sci [serial online] 2022 [cited 2023 Mar 23 ];10:87-90
Available from: https://www.amhsjournal.org/text.asp?2022/10/1/87/347973

Full Text

Introduction

Endometrial stromal sarcomas (ESSs) are rare mesenchymal neoplasms composed of cells morphologically resembling endometrial stroma in the proliferative phase.[1] Endometrial stromal tumors are categorized into the endometrial stromal nodule, low-grade ESS (LG-ESS), high-grade ESS, undifferentiated ESS, and uterine tumor resembling ovarian sex cord tumor (UTROST) by the 4th edition of WHO classification. LG-ESS accounts for <1% of all uterine malignant mesenchymal tumors, and it is the second most common tumor after leiomyosarcoma.[2] It contributes to 0.2% of all uterine malignancies with an annual incidence of 1–2 per million women. The mean age of occurrence is 48–52 years, and 10%–25% of the affected women are in the premenopausal period.[3] Occurrence of ESS primarily in extrauterine location and showing extensive sex cord-like differentiation is rare and hence is reported here.

Case Report

A 48-year-old woman of gravida 2, para 2 and live births 2 presented with a complaint of abdominal pain for 3 months. It was insidious in onset and gradually progressive. Her menstrual cycles were regular. She has had both full-term vaginal deliveries. She had undergone tubectomy 20 years back and laparoscopic cholecystectomy for cholelithiasis 6 years back. Ultrasonogram abdomen showed two infraumbilical, midline, heterogeneous masses, each measuring 5.9 cm × 5.8 cm and 7.2 cm × 3.9 cm with no enhanced vascularity.

Contrast-enhanced computerized tomography imaging of the abdomen and pelvis showed variably thickened, noncommunicating, two, well-defined, oval-shaped, partly solid, and partly cystic masses in the infraumbilical region. The larger mass measured 6.7 cm × 5.8 cm and was adherent to the dome of the urinary bladder. The smaller mass measured 4.5 cm × 3.5 cm and was located beneath the anterior abdominal wall. These findings favored a diagnosis of the infected urachal cyst [Figure 1].{Figure 1}

The patient underwent cystoscopy followed by exploratory laparotomy. Intra-operatively urinary bladder was normal. Multiple omental nodules and cysts were noted. Omentum with the nodules was excised after separating the adhesions from the stomach and intestinal loops.

We received an omentectomy specimen measuring 60 cm × 16 cm × 1.5 cm with six nodules of variable sizes. The largest nodule measured 7 cm × 6 cm × 2 cm and was partly solid and partly cystic. Two of the nodules were completely cystic, measuring 4 cm × 3 cm × 2 cm and 3 cm × 2 cm × 2 cm, respectively. These cysts were multiloculated, had a smooth inner surface, and exuded clear fluid. Three of the nodules were solid, each measuring 1 cm across with a gray pink cut section [Figure 2].{Figure 2}

Histopathology sections studied from the solid and cystic areas showed similar features, comprising sheets of spindle-shaped cells arranged in short fascicles with small arterioles in between. These cells had scant cytoplasm, round to ovoid nuclei that exhibited mild nuclear pleomorphism and indistinct nucleoli. Admixed among these were a few polygonal cells having a moderate amount of eosinophilic to vacuolated cytoplasm. Interspersed amidst the spindle cells were anastomosing cords, trabeculae and nests of darkly stained cells. The stroma had a fine fibrillary collagenous appearance. Necrosis was not seen in the sections studied [Figure 3]. A provisional diagnosis of spindle cell neoplasm, possibly gastrointestinal stromal tumor (GIST), low-grade leiomyosarcoma, and extrauterine ESS (EESS) with sex cord elements were considered.{Figure 3}

Immunohistochemistry (IHC) showed neoplastic spindle cells positive for CD10, estrogen receptor (ER), progesterone receptor (PR), and WT1. Desmin was positive in sex cord-like elements [Figure 4]. Neoplastic cells were negative for cyclin D1, MIC2, CD34, CD117, and DOG1. Ki67 proliferation index was 5%–6%. Based on morphology and IHC findings, a diagnosis of LG-ESS with sex cord elements was diagnosed. The patient was subjected to a thorough radiological evaluation postsurgery to look for primary in the uterus; however, it was not found and the patient remained asymptomatic during 2 years of follow-up.{Figure 4}

Discussion

LG-ESS, also known as endolymphatic stromal myosis, is a malignant tumor composed of cells resembling stromal cells of proliferative phase endometrium, exhibiting infiltrative growth into the myometrium and/or lymphovascular spaces. They are indolent tumors with an excellent prognosis.[4] LG-ESS occurring in extrauterine location is very rare. In a large case series on extrauterine stromal sarcomas reported from MD Anderson Cancer Center, the most common sites were ovaries, rectal wall, pelvic peritoneum, and vagina.[5] Other rare locations include the larynx, lung, and sigmoid colon.[6],[7] A meta-analysis by Buchholz et al. showed rectosigmoid to be the most common primary extrauterine location, and in only two cases, omentum was involved exclusively.[8] The present case showed multiple omental nodules with no involvement of the female genital tract or colon.

The most common clinical presentation includes either an abdominal mass, pelvic mass, pain, vaginal bleeding, or gastrointestinal symptoms such as hematochezia, constipation, diarrhea, and altered bowel habits. Approximately 25% of the diagnosed cases had an initial pathologic diagnosis other than EESS, including GIST, leiomyoma, and sex cord-stromal tumor. The median age at diagnosis is 50 years, with the majority in the fifth decade and in early menopause.[5],[8]

EESS usually occurs in association with endometriosis as reported by Masand et al. where 30 of 63 cases showed foci of endometriosis, and another study showed endometriosis in 15 of 20 cases. Many authors have reported the incidence of EESS along with endometriosis in various locations such as parametrium, omentum, sigmoid mesentery, transverse mesocolon, and ovary.[5],[9] This gives a clue to its pathogenesis. Malignant transformation of endometriosis, although rare, is a well-recognized phenomenon. Yantiss et al. have reviewed 17 cases of endometriosis in the gastrointestinal tract that showed premalignant and malignant transformation, of which endometrial adenocarcinoma accounted for the majority of the malignant tumors.[10] Six cases of vaginal LG-ESS have been reported in the literature not associated with endometriosis. Lauchlan SC has suggested a hypothesis that coelomic epithelium can differentiate into mullerian type of stroma in sites outside of uterus but confined to female genital tracts such as Fallopian tube, ovaries, and pelvic peritoneum.[11] However, in the present case, the extensive search did not yield endometriotic foci. Various hypotheses put forward to explain such cases include (1) gland poor endometriosis, (2) complete replacement by tumor, and (3) de nova malignant transformation of peritoneal or coelomic multipotential epithelial cells.[5] Another interesting hypothesis is the role of hormone replacement therapy (HRT) in the development of EESS, as noted by Masand et al. In their study majority of the postmenopausal women were on long-standing HRT. In a meta-analysis by Buchholz et al., 4 of 20 cases had HRT.[5],[8] Long-term use of vaginal conjugated estrogen cream is also causative as it is known to get absorbed into the bloodstream.[7] The present case, however, did not have a history of HRT. Similar de nova occurrence of EESS has been recorded in the literature in various sites such as lung, larynx, vulva, and vagina.[6]

EESS is a diagnostic challenge when it occurs in extrauterine locations. It is mistaken for other mesenchymal spindle cell neoplasms, such as cellular leiomyoma, leiomyosarcoma, GIST, and solitary fibrous tumors. Despite the characteristic histological findings of spindle-shaped cells arranged in short fascicles with uniform round-to-ovoid nuclei and rare mitoses, a panel of IHC markers are needed for definitive diagnosis. The present case, in addition, demonstrated sex cord elements to add to the complexity of diagnosis. They were arranged as nests, trabeculae, and anastomosing cords of epithelioid cells with variable amounts of cytoplasm, round nucleus, small nucleoli, and minimal mitotic activity. This recapitulates the ovarian granulosa cell or Sertoli cell tumors.[6] The presence of sex cord-like elements has not been reported in an extrauterine ESS, and also multiple solid and cystic nodules exclusively in the omentum, without involving the uterus or genital tract. Due to its unusual presentation and location, the present case is the first in its nature.

The landmark publication by Clement and Scully in 1976 divided uterine tumors with sex cord elements into two groups. Group I tumors are well-recognized endometrial stromal tumors with focal epithelial-like differentiation resembling that seen in sex cord tumors. These tumors were mostly poorly circumscribed large mural masses. The focal sex cord-like differentiation was manifested by cords, trabeculae, nests, and tubules of epithelial-like cells; they were conventionally called endometrial stromal tumors with sex cord-like elements. As per the 2014 WHO classification, both endometrial stromal nodule and LG-ESS can show sex cord-like differentiation. In addition to sex cord differentiation, LG-ESS are known to exhibit variant morphology such as smooth muscle differentiation, fibromyxoid change, and endometrioid type of glands; however, their behavior is similar to LG-ESS. Group II tumors differed from Group I tumors by having a predominant or exclusive pattern reminiscent of an ovarian sex cord tumor. Most of these tumors were single, well-circumscribed, yellow to tan, mural masses of 4–10 cm in diameter, and appeared benign with no recurrence during postoperative follow-up of 4 months to 7 years.[12] They were called UTROSCT according to the 2014 WHO classification and do not contain any recognizable stromal component. They behave in a benign fashion.[13]

The present case showed positive IHC for CD10, ER, PR, and WT-1, with desmin highlighting the sex cord-like elements. Negative markers include CD 34, CD 117, DOG 1, cyclin D1, and MIC1. Son et al., in his study on primary colonic EESS, has reported a similar IHC pattern.[14] LG ESS are positive for CD10, ER, and PR with variable expression of cyclin D1. High-grade ESS are negative for CD10, ER, and PR and show strong diffuse positivity for cyclin D1. Desmin and h-caldesmon are typically positive in areas showing smooth muscle and sex cord-like differentiation.[2]

ESSs demonstrate variable genetic alterations, 50% of them show t(7;17)(p15;q21), which results in the JAZF1-SUZ12 fusion gene, which is also seen in ESS displaying fibromyxoid, epithelioid, smooth muscle, and sex cord-like differentiation. The next most common genetic alteration is t (6;10;10)(p21;q22;p11) resulting in EPC1-PHF1 gene. The rearrangements involving 6p21 are usually associated with sex cord-like differentiation.[2] Kundu et al. have reported the JAZF1-SUZ12 fusion gene in a case of colonic EESS.[15] In a study by Amador-Ortiz et al. involving six cases of EESS, JAZF1-JJAZ1 gene fusion was detected by both reverse transcriptase–polymerase chain reaction and by interphase fluorescent in situ hybridization in one case only. The low prevalence of these gene aberrations limits the clinical utility of genetic testing in EESS.[16]

In view of the rarity of EESS, treatment is usually based on the same guidelines as of uterine ESS. Surgical resection remains the primary treatment combined with a hysterectomy and bilateral salpingo-oophorectomy to rule out primary uterine ESS or ovarian ESS. Due to the abundant expression of ER and PR, hormone therapy is commonly employed to suppress the stromal proliferation in ESS. However, three different cases of EESS, which were positive for ER and PR, showed disease progression with hormone therapy.[17] The possible explanations for the unresponsiveness of EESS for hormone therapy are variation in the concentration of sex steroid receptors and relative expression of PR isoforms PR-A and PR-B between endometrial and extrauterine stromal sarcomas, the latter being less hormone responsive.[3] Not many reports are available on the efficacy of adjuvant therapy such as radiotherapy, chemotherapy, and hormone therapy, and hence further investigations are needed in this direction.

In summary, ESS can occur in varied extrauterine locations, without any evidence of endometriosis and without primary genital tract ESS. It may occur as solid or cystic mass and can show sex cord-like differentiation. An unexpected location of EESS may make the diagnosis challenging, and IHC plays an important role in it. EESS should be considered in the differential diagnosis of any abdominal spindle cell tumor. Surgical excision remains the main treatment modality.

Acknowledgment

I thank Dr. C. S. Premalatha of Kidwai Memorial Institute of Oncology, Bengaluru, for her valuable support in obtaining IHC stains.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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