Endometrial stromal sarcomas with extensive endometrioid glandular differentiation: report of a series with emphasis on the potential for misdiagnosis and discussion of the differential diagnosis

Aims:  To describe a series of endometrial stromal sarcomas with large numbers of endometrioid-type glands.
Methods and results:  The eight tumours occurred in patients aged 42–74 years. In three cases, the neoplasm arose in the uterine corpus and in the others there was either an extrauterine origin or the origin could not be determined since multiple sites were involved. In four cases, glands were present throughout the neoplasm and in the others there were areas of typical endometrial stromal sarcoma without glands. In one case, glands were present only in the recurrent neoplasm. The malignant stromal component comprised, for the most part, typical endometrial stromal sarcoma. In two patients, repeated biopsy specimens from the vagina or cervix were initially diagnosed as endometriosis, and in some cases there was a significant delay in diagnosis. Apart from endometriosis, other diagnostic considerations, depending on the tumour location and exact morphology, included adenomyosis, adenosarcoma and carcinosarcoma.
Conclusions:  Endometrial stromal sarcoma with extensive endometrioid glandular differentiation is rare. The presence of glands often results in diagnostic difficulty with a significant risk of misdiagnosis or delay in diagnosis. It is likely that some cases reported in the literature as aggressive endometriosis represent this entity.     

Endometrial stromal sarcoma of the rectosigmoid colon arising in extragonadal endometriosis and revealed by portal vein thrombosis

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 76% of cases, and extragonadal sites are identified in 24%. Endometrioid carcinoma is the most common histologic type; sarcoma is very rare. We report a case of low-grade endometrial stromal sarcoma of the rectosigmoid colon presenting with epigastric pain due to portal vein thrombosis. This tumor arose from extragonadal endometriosis in a 61-year-old woman and was treated by surgical resection. The main differential diagnosis of this unusual colonic neoplasm includes primary mesenchymal tumors, such as gastrointestinal stromal tumors.     

Two Previously Unemphasized Features of Endometriosis: Micronodular Stromal Endometriosis and Endometriosis with Stromal Elastosis

This report draws attention to two unusual features of the stromal component of endometriosis that can create problems in diagnosis. One of these is the exclusive presence of endometriotic stroma, so-called stromal endometriosis, that can occasionally take the form of microscopic nodules of endometriotic stroma on the pelvic peritoneum and other locations. This finding, which we refer to as a micronodular stromal endometriosis, can be overlooked entirely or lead to confusion with peritoneal involvement by low-grade endometrial stromal sarcoma. The other finding we describe is the presence of a prominent elastotic stromal response to endometriosis that can occasionally obscure or even focally obliterate the typical endometriotic stroma. This finding, although nonspecific, can be a diagnostic clue to the presence of endometriosis, especially when accompanied by the presence of the typical endometriod glands of that lesion. Int J Surg Pathol 8(3):223-227, 2000     

Parenchymatous pulmonary endometriosis - metastases of a low-grade endometrial stromal sarcoma?

Based on the data of a case of parenchymatous endometriosis of the lung in which three and a half years later a low-grade endometrial stromal sarcoma of the uterus was diagnosed the origin of this disease is discussed. The follow up of this patient gave the impression that the pulmonary nodules were early metastases of low-grade endometrial stromal sarcoma, which was initially not detected in the routine gynecologic examination. Furthermore, as histological and immunohistochemical examinations are not sufficient to distinguish reliable between endometriosis of the lung and pulmonary metastases from low-grade endometrial stromal sarcoma. In literature, in none of the few cases of parenchymatous pulmonary endometriosis a hysterectomy was performed to exclude a low-grade endometrial stromal sarcoma. Thus, parenchymatous pulmonary endometriosis nodules might be metastases and their occurrence should cause the treating physician to consider a distant metastatic spread from low-grade endometrial stromal sarcoma.     

Endometrial stromal sarcoma of the sigmoid colon arising in endometriosis: a case report with a review of literatures

Most of malignant tumors arising in ovarian and extraovarian endometriosis are carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in intestinal endometriosis are rarely described, but its clinicopathologic features have not been well characterized. Here we report a case of endometrial stromal sarcoma of the sigmoid colon arising in endometriosis with a review of six additional cases of endometrial stromal sarcoma arising in intestinal endometriosis found in English literatures. The patients ranged in age from 36 to 64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some patients had a previous history of endometriosis. Most of the tumors arose in the rectosigmoid colon. The histologic features were the same as their uterine counterpart. No death of disease had been reported. This rare tumor should not be confused with gastrointestinal stromal tumor clinically and histologically.     

Symptomatic intracavitary (noninvasive) cardiac metastasis from low grade endometrial stromal sarcoma of the uterus.

We report a 49-year-old woman who was operated upon 33 years ago for uterine endometrial stromal sarcoma of low-grade malignancy. The patient showed obstruction of the right ventricular outflow tract. An echocardiogram and MRI showed that a mass emanating from the inferior vena cava filled the right atrium, the right ventricle, and part of the pulmonary artery. The entire intracavitary neoplasm was successfully removed and diagnosed as low-grade endometrial stromal sarcoma. To our knowledge, this is the second report of a low-grade endometrial stromal sarcoma reaching the heart via the inferior vena cava. In this case an intracavitary metastasis may be a feature indicating the progression of the endometrial stromal sarcoma. Therefore, this neoplasm should be included in the differential diagnosis of cardiac intracavitary neoplasms. Patients affected by this tumor may benefit from early identification and resection of the obstructing neoplasm.     

Extrauterine low-grade endometrial stromal sarcoma: Report of three cases

Three cases of rare low-grade endometrial stromal sarcoma of the extrauterine tissue are presented. Each one occurred In the ovary, pelvic and abdominal cavities. Two were associated with endometriosls. Histologically, the tumors were characterized by an infiltrative and diffuse proliferation of uniform round or oval cells, abundant small vessels, low mitotic activity, the presence of foam cells and vascular Invasion. lmmunohistochemically, all tumors expressed vimentin, muscle markers (desmin, muscle-specific actin and α-smooth muscle actin) and progesterone receptors. Two tumors were diploid and one was aneuploid by flow cytometry. All patients were well with no evidence of disease 16–39 months after surgery. It Is suggested that this neoplasm may arise with or without endometriosis under hormonal Influence. This rare variant of Müllerian tumors should not be confused with adenosarcoma and soft tissue tumors, such as smooth muscle tumors and solitary fibrous tumor.     

Endometrial Stromal Sarcoma Presenting as Prevesical Mass Mimicking Urachal Tumor

Endometrial stromal sarcoma (ESS) is a mesenchymal neoplasm that usually occurs as a primary tumor of the uterine corpus, but rarely arises in other sites, such as the ovary, pelvic cavity, mesentery, omentum and intestine. Herein, we present a rare case of low-grade ESS presented as prevesical mass. A 60-yr-old woman who had undergone total hysterectomy for endometriosis eleven years ago was presented with incidentally detected prevesical pelvic mass. Since malignant transformation of urachal remnants was possible, the mass was suspected to be a urachal tumor. Extraction of the mass was performed, and the histopathologic diagnosis was low-grade ESS. In summary, prevesical tumor is rare but in patients with endometriosis, we suggest endometriosis and its possible malignant changes should be taken into account in the differential diagnosis of prevesical mass.     

Endometrial stromal sarcoma of the small bowel

Endometrial stromal sarcoma (ESS) is a rare mesenchymal neoplasm of the uterus, which is predominantly composed of endometrial stromal cells. When this feature is encountered in the extragenital area, the diagnosis is sometimes difficult especially if endometriosis is not present. We report a case of ESS arising in the small bowel without associated endometriosis in a 75-year-old woman and review the literatures for 16 cases of extrauterine extraovarian ESS. The most common site of the extrauterine extraovarian ESS is the gastrointestinal tract (8/16 cases). It is intimately associated with endometriosis (12/16 cases) as the case of ovarian ESS. Most ESSs were immunoreactive for CD10 (5/5 cases), progesterone receptor (10/10 cases), and estrogen receptor (9/11 cases), and negative for CD34 (0/7 cases). It may have a higher tendency for dissemination beyond its site of origin (12/16 cases) than its uterine counterpart. In conclusion, a careful morphological examination combined with immunohistochemical studies and consideration of ESS in the differential diagnosis would help in obtaining an accurate diagnosis in these rare circumstances.     

The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects

Although the histologic diagnosis of endometriosis is usually straightforward, many diagnostic problems can arise as a result of alterations or absence of its glandular or stromal components. The diagnostic difficulty in such cases can be compounded by tissue that is limited to a small biopsy specimen. The appearance of the glandular component can be altered by hormonal and metaplastic changes, as well as cytologic atypia and hyperplasia. Although the last 2 findings are often referred to collectively as "atypical endometriosis," they should be separately recognized as their premalignant potential likely differs. In some cases, the endometriotic glands are sparse or even absent (stromal endometriosis). The stromal component can be obscured or effaced by infiltrates of foamy and pigmented histiocytes, fibrosis, elastosis, smooth muscle metaplasia, myxoid change, and decidual change. Occasional findings in endometriosis that may raise concern for a neoplasm include necrotic pseudoxanthomatous nodules, polypoid growth (polypoid endometriosis), bulky disease, and venous, lymphatic, or perineural invasion. Inflammatory and reactive changes within, adjacent to, or at a distance from foci of endometriosis can complicate the histologic findings and include infection within endometriotic cysts, pseudoxanthomatous salpingitis, florid mesothelial hyperplasia, peritoneal inclusion cysts, and Liesegang rings. The histologic diagnosis of endometriosis can also be challenging when it involves an unusual or unexpected site. Five such site-specific problematic areas considered are endometriosis on or near the ovarian surface, superficial cervical endometriosis, vaginal endometriosis, tubal endometriosis, and intestinal endometriosis, including the important distinction of an endometrioid carcinoma arising from colonic endometriosis from a primary colonic adenocarcinoma. Finally, endometriotic foci can occasionally be intimately admixed with another process, such as peritoneal leiomyomatosis or gliomatosis, resulting in a potentially confusing histologic appearance.     

Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas

Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.     

Uterine epithelioid endometrial stromal sarcoma presenting as a "cervical polyp"

Although appearance of conventional uterine endometrial stromal sarcoma is easily recognized on histology, it may uncommonly assume unusual appearances such as uterine tumor resembling ovarian sex-cord tumor, thereby hindering its diagnosis. Recently, its manifestation as an epithelioid neoplasm was described. In this report, we detail yet another instance where this tumor adopted an epithelioid morphology, presenting itself as a polyp extruding from the cervical os in a 41-year-old Chinese woman. Both the polypectomy and subsequent hysterectomy specimens revealed a predominant proliferation of CD10-negative, caldesmon-negative, and CD117-positive epithelioid cells set within a stroma containing vascular proliferation resembling endometrial stromal tumor. Areas of typical low-grade endometrial stromal sarcoma containing spindle cells that were focally positive for CD10 and negative for CD117 were present in close association with the epithelioid areas. The differential diagnoses and possible implication of CD117 positivity are discussed.     

Hepatic endometrial stromal sarcoma

Endometrial stromal sarcomas are rare tumors that may recur or metastasize many years after their initial presentation. Though most recurrences are within the pelvis, distant metastases can occur, and are most common to the lungs. Metastases to the liver are extremely rare. Herein we report two cases of endometrial stromal sarcoma with metastases to the liver without a prior history of endometriosis, accompanied by their histology, immunohistochemistry, and molecular analysis in the context of a relevant literature review.     

Uterine endometrial stromal sarcoma with smooth muscle and glandular differentiation

This report describes a uterine tumour exhibiting areas of both endometrial stromal and smooth muscle differentiation. There was extensive intravascular permeation within the myometrium as well as extrauterine vascular involvement. The endometrial stromal component had a myxoid appearance and the smooth muscle component exhibited the typical features of intravenous leiomyomatosis. An additional feature was the presence of numerous benign endometrial-type glands within the neoplasm. In many areas a "zoning" phenomenon was present, with endometrial glands surrounded by endometrial stroma, which was in turn surrounded by smooth muscle. This unique combination of endometrial glands, endometrial stroma, and smooth muscle has, to the best of our knowledge, not been described previously and adds to the morphological spectrum of mixed endometrial stromal-smooth muscle tumours. This report discusses the differential diagnosis of this lesion, which has been designated a low grade endometrial stromal sarcoma with smooth muscle and glandular differentiation.     

The Peritoneal Fluid Levels of Interleukin-12 in Women with Endometriosis

PROBLEM: Interleukin-12 (IL-12) is produced mainly by monocytes/macrophages, and it induces proliferation and cytotoxicity of T-cells and natural killer cells. In women with endometriosis, natural killer cell activity in the peritoneal fluid is significantly decreased. We aimed to measure the peritoneal fluid level of IL-12 in endometriosis. METHOD OF STUDY: We measured IL-12 levels in peritoneal fluid samples from women with or without endometriosis and in supernatants from endometrial stromal, ovarian stromal, and mesothelial cell cultures, using a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: The median concentration of IL-12 in the peritoneal fluid of women with endometriosis was 1.1 pg/ml (range, 0.2–5.5) and was 1.6 pg/ml (range, 0.4-2.8) in women without endometriosis, not a statistically significant difference. IL-12 was not detected in the supernatants of endometrial stromal, ovarian stromal, and mesothelial cell cultures. CONCLUSION: Concentrations of IL-12 in the peritoneal fluid of women with or without endometriosis are low, but they are detectable and are not affected significantly by the presence of endometriosis.     

Clinicopathologic and immunohistochemical study on 8 cases of malignant mixed müllerian tumor

The clinico-pathological features of eight cases of malignant mixed müllerian tumor, a rare neoplasm composed of an admixture of epithelial and stromal elements, are reported. Four of the tumors located in the endometrium, three in the cervix and one in the ovary. Microscopically, the epithelial elements ranged from poorly to well differentiated adenocarcinoma. Homologous stromal sarcoma cells were present in six tumors and heterologous elements were also seen in the other two tumors. Immunohistochemical studies showed diffuse cytoplasmic staining of keratin in the epithelial elements of all the eight cases. Sarcomatous cells were positive focally for keratin in four spindle cell sarcoma cases. Desmin immunoreaction was moderately positive in the sarcomatous element of four neoplasms. Follow-up result was available in 7 patients of whom 3 survived and 4 died from recurrence or metastasis. Immunohistochemical findings support the stem cell origin of this tumor.     

Endometrioseassoziierte Tumorerkrankungen des Ovars

Endometriosis is a frequent gynecological disease of unknown etiology and pathogenesis. It affects the gynecological organs and the peritoneum with varying frequency and can lead to severe symptoms, mainly pain and to infertility. Despite the fact that causal therapy is not feasible diagnostic and therapeutic procedures are necessary in many cases. In a small percentage of cases endometriosis is associated with neoplastic disease and in some cases it might develop into a neoplasm via the stage of atypical endometriosis, notably in the ovaries. Tumors which are most frequently associated with endometriosis are endometrioid carcinoma, clear cell carcinoma, and low grade serous carcinoma. According to some authors tumors associated with endometriosis have a better prognosis than those without. Other tumors are Mullerian adenosarcoma, endometrioid stromal sarcoma, and seromucinous borderline tumor. In addition to the morphological findings more recent molecular findings serve to demonstrate the origin of the different types of carcinoma from endometriosis. In both endometrioid and clear cell carcinoma, loss of heterozygosity (LOH) can be found in different gene loci. Mutations in CTNNB1 (beta catenin), PTEN, KRAS and ARID1a genes have been demonstrated in endometrioid carcinoma. Cases of clear cell carcinoma have been characterized by mutations of ARID1a gene, PIK3CA and less frequently PPP2R1A and KRAS.     

Endometrial stromal sarcoma of the retroperitoneum

Endometrial stromal sarcoma (ESS) is an uncommon neoplasm whose occurrence outside the uterus is extremely rare in the absence of metastasis or extension of a primary uterine neoplasm. When ESS occurs in such locations it is often associated with the uterine adnexa or serosal surface of various organs. Although rare, ESS is usually considered in the differential diagnosis of spindle cell neoplasms in the female patient. We report a case of ESS arising in the retroperitoneum and discuss the morphologic and immunohistochemical features in the context of the differential diagnosis of a retroperitoneal low-grade spindle cell neoplasm occurring in the female patient.