Disseminated Peritoneal Endometriosis Evolving to High-Grade Endometrial Stromal Sarcoma: A Case Report with Review of the Literature

Introduction

Endometrial stromal sarcomas (ESS) are uncommon mesenchymal neoplasms of the uterus, composed of cells closely resembling normal proliferative endometrial stromal tissue. ¹ Endometrial stromal sarcomas account for 0.2% of all uterine malignancies and 7%–15% of all uterine sarcomas. ² Endometriosis is a known risk factor for development of ESS and in few ESS patients, a clinical history and/or histologic evidence of endometriosis is present. ³

This article describes a case of a 35-year-old female presenting with lower-abdominal pain, diagnosed as disseminated peritoneal endometriosis at several occasions, who, 4 years after her initial diagnosis, developed a high-grade ESS (HG-ESS).

Case

A 35-year-old female presented with dull, continuous lower-abdominal pain that she had for 3 months prior and for secondary infertility. Examination revealed that was lower-abdominal tenderness but no rigidity. Ultrasonography of the abdomen and pelvis did not reveal any abnormality. Her serum cancer antigen (CA)–125 level was raised. A laparoscopic examination was performed, which showed bowel adhesions. A biopsy taken from the bowel adhesions revealed the presence of endometrial glands surrounded by stroma and scattered hemosiderin-laden macrophages. Based on these histopathologic findings, a diagnosis of endometriosis was offered. She received 2 doses of a gonadotropin-releasing hormone analogue. Later, she did not follow up.

Two years still later, this patient presented again with severe abdominal pain and distension. Clinical examination revealed massive ascites. Magnetic resonance imaging was ,performed which showed gross ascites with peritoneal enhancement and peritoneal thickening with nodular deposits in the pelvis. Her serum CA-125 level was within normal limits. The left ovary was normal, while the right ovary had a small cystic lesion measuring 2 cm in maximum diameter. Cytologic examination of the ascitic fluid did not show any malignant cells in 3 consecutive samples over 3 months. A laparoscopic evaluation was planned; however, owing to her dense adhesions, a laparotomy had to be performed, which revealed massive hemorrhagic ascites with multiple nodular deposits on the peritoneum, over the uterus, on both ovaries, on the bowel, bladder base, and on the subdiaphragmatic surface. Based on a clinical suspicion of malignancy, a total abdominal hysterectomy (TAH) with a bilateral salpingo-oophorectomy (BSO) was performed. Simultaneously, deposits present over the bowel and urinary bladder were also sampled.

Microscopic examination of multiple sections from the bilateral ovaries, and fallopian tubes, as well as the bowel, serosal, and urinary-bladder nodules showed of benign-appearing endometrial glands surrounded by abundant endometrial stroma and a few hemosiderin-laden macrophages, mainly on the serosal aspect. No significant pleomorphisms or atypical mitotic figures were noted. Based on these findings, a diagnosis of disseminated peritoneal endometriosis was rendered (Fig. 1). On immunohistochemistry, the endometrial glands and stroma were highlighted by estrogen and progesterone receptor immunostaining (Fig. 2). The patient was started on parenteral leuprolide (3.75 mg) and oral letrozole (2.5 mg, once daily). Intramuscular injection of depot medroxyprogesterone acetate (150 mg every month) was also prescribed and a monthly follow-up was advised. However, she was again lost to follow-up.

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FIG. 1.

Panel of photomicrographs from the total abdominal hysterectomy and bilateral salpingo-oophorectomy specimen. (A) Section showing a dilated endometrial gland surrounded by endometrial stroma in the thickened serosa outside the myometrium (hematoxylin and eosin [H&E], 2 × ). (B) Section showing a benign endometrial gland surrounded by endometrial stroma and foci of calcifications in the thickened peritoneum over the ovary (H&E, 2 × ). (C) Section showing a benign endometrial gland surrounded by endometrial stroma in the thickened serosa over the fallopian tube (H&E, 2 × ); (D) Section from the bowel nodule showing benign endometrial glands surrounded by endometrial stroma (H&E, 2 × ). (E) Higher magnification to highlight the benign endometrial glands (H&E, 10 × ). (F) Higher magnification to highlight the bland appearance of the surrounding endometrial stroma (H&E; 20 × ).

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FIG. 2.

Estrogen receptor (ER, left) and progesterone receptor (PR, right). Immunohistochemistry for ER and PR showing nuclear positivity in the endometrial glands as well as the surrounding stroma (10 × ).

One year later, the she presented to the emergency room with pain in her abdomen, shortness of breath, and constipation. A contrast-enhanced computerized tomography (CECT) revealed a 5.2 × 5.7–cm heterogeneous lesion in her pelvis and another heterogeneous lesion measuring 8.8 × 6.1 cm in the gastro-splenic region with a radiologic suggestion of endometriosis or peritoneal malignancy. The patient was investigated further for invasive/infiltrative endometriosis. Proctoscopy showed normal mucosal appearance. There was no evidence of endometriosis. Cystoscopy did not show any endometriotic deposits, calculi, or diverticula in the urinary bladder. Colonoscopy revealed erythematous and hyperemic mucosa of terminal ileum and splenic flexure. A laparotomy was planned but had to be postponed because she had a urinary-tract infection with Escherichia coli.

Results

One month later, she presented with severe pain abdomen and breathlessness. Clinical examination revealed hemorrhagic shock with hemoperitoneum. An exploratory laparotomy followed by resection of ruptured gastro-splenic mass was performed. However, despite several attempts of resuscitation, this patient could not be revived.

Grossly, the ruptured gastro-splenic mass predominantly was composed of hemorrhagic tissue. All of the tissue was sampled. The sections showed predominantly hemorrhage and large areas of necrosis. However, a few areas showed sheets of viable tumor cells depicting moderate nuclear pleomorphisms, oval-to-elongated nuclei, fine chromatin, occasional prominent nucleoli and scanty cytoplasm. These cells were interspersed with numerous small arterioles. Frequent mitotic figures were noted (7–8/10 high-power fields; Fig. 3). Based on these features a diagnosis of HG-ESS, possibly evolving from disseminated endometriosis, was made.

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FIG. 3.

Panel of photomicrographs from the gastro-splenic mass. (A) Section showing predominantly fresh hemorrhage and necrosis with nuclear debris (hematoxylin and eosin [H&E], 10 × ). (B) Section showing viable tumor cells adjacent to the necrotic foci (H&E; 10 × ). (C and D) Higher magnifications to show the viable tumor cells arranged in sheets with interspersed spiral arteriolelike vascular channels (H&E, 20 × ). (E) Section showing sheets of tumor cells with mild-to-moderate nuclear pleomorphism, prominent nucleoli and scant to moderate cytoplasm (H&E, 40 × ). (F) Section from the viable tumor area showing scattered mitotic figures (H&E; 40 × ).

Discussion

Endometrium is a specialized tissue of the human body; this tissue is able to proliferate, shed, and regenerate. Endometriosis is defined as the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. Depending on the area identified, endometriosis can be categorized as endopelvic or extrapelvic. Despite the rarity of extrapelvic endometriosis, cases of endometriosis involving the gastrointestinal tract, urinary tract, upper- and lower-respiratory tract, diaphragm, pleura, pericardium, and as abdominal scars have been reported in the literature. ⁴

In less than 1% of women, these endometriotic lesions can undergo malignant transformation. The criteria for diagnosis of a malignancy arising in endometriosis are: (1) demonstration of a clear endometriotic area in the proximity of the tumor; (2) no other primary site for the tumor; and (3) an histologic appearance consistent with an origin from endometriosis. ³ The malignancies that might evolve from preexisting endometriosis include epithelial ovarian cancers, other Müllerian-type tumors including Müllerian-type mucinous borderline tumors and serous borderline tumors, and sarcomas. ² Most common epithelial malignancies associated with endometriosis include endometrioid adenocarcinoma and clear cell carcinoma. Among the sarcomas, the most-common are the adenosarcomas and ESS. ²

The World Health Organisation has classified ESS into 3 categories: (1) low-grade ESS (LG-ESS); (2) HG-ESS; and (3) undifferentiated uterine sarcoma (UUS). ¹ The exact etiopathogenesis is not yet clear, however, two hypotheses have been put forward. One hypothesis is the direct malignant transformation of endometriosis. There are reports in the literature documenting ESS in association with endometriosis. However, the exact incidence of ESS developing in endometriosis is not known. The other theory is origin as a de novo tumor, potentially derived from Müllerian cells. There are a few reports suggesting the origin of ESS from submesothelial pluripotent cells, which are considered to be widely distributed in the abdominal and pelvic cavities. To summarize, ESS may originate from endometriosis or from metaplasia of the pluripotent Müllerian cells. ²

ESS show immunopositivity for CD10, estrogen receptor (ER), and progesterone receptor (PR) and are negative for desmin, smooth-muscle actin and S-100. For delineation of high-grade from low-grade ESS, ER, PR, and CD10 are helpful, because they typically show diffuse positivity in LG-ESS but are often lost in HG-ESS, while cyclin-D1 shows diffuse strong positivity in HG-ESS. ⁵

In the present case, the patient had been diagnosed as having endometriosis after examination of a biopsy from her bowel adhesions. Subsequently, she underwent a TAH with BSO with resection of peritoneal deposits, which, on histopathology, revealed disseminated peritoneal endometriosis. Two years later, histopathologic examination of the gastro-splenic mass revealed development of HG-ESS.

ESS can occur many months to years after the original diagnosis of endometriosis, potentially creating a diagnostic challenge. ⁶ The new ESS classifications include LG-ESS with underlying t(7;17) resulting in JAZF1–SUZ12 or JAZF1-JJAZ1 fusions. ⁷ HG-ESS is defined as an ESS with t(10;17)(q22;p13) rearrangement leading to YWHAE-FAM22 or YWHAE–NUTM2A/B gene fusions, while UUS is a “wastebasket category” that does not harbor any specific chromosomal translocations. Other less-common gene fusions, including, PHF1-JAZF1, PHF1-EPC1, MEAF6-PHF1, ZC3H7-BCOR and MBTD1-CXorf67 have also been reported in LG-ESS.^5–8

Additionally, a thorough review of literature was also performed to identify all the previously reported cases of extragenital ESS evolving in preexisting or coexisting endometriosis (with documented evidence of preexisting/concomitant endometriotic foci). Table 1 enumerates 24 such cases of extragenital ESS developing from endometriosis.^9–31 There are only 2 such previously reported cases documenting development of ESS in the peritoneum with preexisting endometriosis.^10,19

Conclusions

The reported frequency of malignant transformation in endometriotic lesions is quite low; however, their prompt recognition is important, as such developments might prove fatal, as in the current case. This case highlights the importance of close follow-up of patients with endometriosis to ensure an early diagnosis of malignant transformations.