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Multicystic endometrial stromal sarcoma
RADIOLOGIC-PATHOLOGIC CORRELATIONS
Multicystic Endometrial Stromal Sarcoma Delia Pe´rez-Montiel, MD, Arturo Albrandt Salmeron, MD, and Hugo Domı´nguez Malagon, MD Endometrial stromal sarcoma usually has the gross appearance of a single nodule, multiple masses, or a poorly demarcated lesion with occasional cystic degeneration; however, a multilocular form has not been described in the literature. We report the case of a 25-year-old woman with a cystic multilocular lesion with thin septae measuring 8 cm, discovered by a pelvic ultrasonography. Grossly, it was a multicystic mass located in uterine fundus that was attached to myometrium and showed infiltrating borders. We propose that cystic endometrial stromal sarcoma should be included in the differential diagnosis of cystic uterine tumors. Ann Diagn Pathol 8: 213-218, 2004. © 2004 Elsevier Inc. All rights reserved. Index Words: Endometrial stromal sarcoma, cystic tumors, uterus
E
NDOMETRIAL stromal sarcoma is a rare tumor that generally presents as a diffuse process involving the uterus. Grossly, this lesion can present as a single nodule, multiple masses, or a poorly demarcated pink, tan, or yellow diffuse thickening of the myometrium without any clear demarcation. Cystic degeneration with hemorrhage can be seen in some cases, but occurrence as a multiloculated cystic mass has not been reported. Clinical History
A 25-year-old woman was admitted for evaluation of pelvic pain and a mass of 2 months’ duration. She had been pregnant four times with normal vaginal deliveries. On physical examination, the patient had a palpable mass in the pelvic region that was mobile and not painful. Laboratory findings included CA125 of 9.0 U/mL (normal range, 0 to 21 U/mL) and ␣-fetoprotein of 1.4 ng/mL (normal range, 0 to 1.85 ng/mL). A simple hysterectomy was performed. Eight months later the patient is well and free of disease.
From the Departments of Surgical Pathology and Diagnostic Radiology, Instituto Nacional de Cancerologia, Mexico City, Mexico. Address reprint requests to Delia Pe´rez–Montiel, MD, Instituto Nacional de Cancerologia, Av San Fernando #22 Col Seccion XVI, Delg Tlalpan, Mexico City 14080. © 2004 Elsevier Inc. All rights reserved. 1092-9134/04/0804-0004$30.00/0 doi:10.1053/j.anndiagpath.2004.04.004
Radiologic Findings An abdominal ultrasonography along the axial level with high resolution in real-time gray scale and Doppler color disclosed a cystic lesion that measured 8.2 ⫻ 6.3 cm with smooth and welldefined borders. The lesion showed septae with variable thickness surrounding anechoic cavities without ecogenic images inside of them (Fig 1). The lesion was attached to the round ligament and it was not possible to determine if it arose from the uterine corpus or ovary. Doppler study showed a lesion with peripheral vascularity without low or high flow inside of the multicystic lesion. The septa were also avascular. Outside the mass the peripheral vascularity was low (Fig 2). The ultrasonographic diagnosis was endometrial cyst versus complex ovarian cyst. Gross Findings At surgery, the ovaries were grossly normal, but the uterine corpus was increased in size with an irregular surface in the fundus. Grossly, the uterine surface was multilobulated and smooth; the cut surface showed an 8 ⫻ 6 ⫻ 6 cm multicystic mass situated in the uterine fundus extending to lateral cornu. This lesion was attached to the myometrium and consisted of multiple cysts containing clear fluid; the cyst walls were thin and tanslucent (Fig 3). The rest of the uterus was grossly normal. Pathologic Findings Microscopically, the cyst walls were surrounded by sheets of small cells of relatively uniform size,
Annals of Diagnostic Pathology, Vol 8, No 4 (August), 2004: pp 213-218
213
214
Pe´ rez-Montiel, Sameron, and Malagon
Figure 1. Abdominal ultrasonography disclosed a cystic lesion with smooth and well-defined borders. Septa of variable thickness are seen surrounding anechoic cavities.
with scant amphophylic cytoplasm (Fig 4). The nuclei were round to ovoid with finely dispersed chromatin. Other areas showed epithelioid cells with ample eosinophilic cytoplasm. There were 1 to 2 mitoses per 10 high power fields. The cystic cavities were devoid of a lining. The tumor showed
Figure 2. Same image as Fig 1 with Doppler study showed a lesion with peripheral vascularity without low or high flow inside the multicystic lesion. Septa were also avascular.
focal invasion of the myometrium by tongues of tumor cells larger than 3 mm. No vascular invasion was identified. Immunohistochemical studies were performed; the tumor cells were reactive for CD10 (DAKO, Carpinteria, CA; monoclonal 1:15), actin (DAKO;
Multicystic Endometrial Stromal Sarcoma
215
Figure 3. Uterine corpus with multicystic mass situated in the uterine fundus.
monoclonal 1:50), and focally for desmin (DAKO, monoclonal 1:100). They were negative for AE1/ AE3 cytokeratin (Biogenics, San Ramon, CA, monoclonal 1:50), S-100 protein (DAKO, polyclonal 1:800) and EMA (DAKO, monoclonal 1:80) (Fig 5). Discussion Endometrial stromal lesions account for less than 10% of the nonepithelial tumors of the uterine corpus.1 In the series from the Mayo Clinic,2 endometrial stromal sarcomas represent 10% of all uterine sarcomas. Age at presentation has shown a wide range, from teenagers to elderly women, but the median age is 39 years. No specific ultrasonographic data has been reported for these tumors. The findings are very similar to that of other mesenchymal or epithelial uterine tumors. The most frequent benign uterine lesions that can present with a cystic image on ultrasonography include degenerated leiomyomas, pyometra, hydrocolpos/hematocolpos, uterus didelphus, adenomyosis, and lipoleyomioma. Malignant uterine neoplasms with an ultrasonographic cystic appearance include endometrial carcinoma, leiomyosarcoma, and trophoblastic invasive disease.
Grossly, endometrial stromal sarcomas are generally solid, soft, and tan to gray. They are generally localized in the myometrium, are well circumscribed, and sometimes have a polypoid component. They frequently exhibit foci of necrosis, hemorrhage, and may also show focally some degree of microscopic cystic degeneration, but the development of a large multicystic mass has not been described previously. Differential diagnosis for this tumor includes lesions with gross degenerative cystic changes such as leiomyoma, endometrial stromal nodules, adenomatoid tumor, epithelial cyst, mucinous metastatic carcinoma, or tumors with cystic areas such as lymphangioma, hydatidiform mole, or teratomas.
Table 1. Nonphysiologic Adnexal Masses Endometrioma Tuboovarian abscess Dermoid cyst Ectopic pregnancy Paraovarian cyst Serous/mucinous cystadenoma Peritoneal inclusion cyst Massive ovarian swelling Hydrosalpynx
216
Pe´ rez-Montiel, Sameron, and Malagon
Figure 4. (A) Septae of the lesion shows uniform short spindle cells without lining. (B) Cystic lesion in relation to the myometrium. The cyst wall contains uniform short spindle cells.
Other lesions that have been reported as cystic or multicystic in the uterus are endosalpingiosis,3 adenomyosis,4 and adenofibroma.5 Another condition that must be considered in the differential diagnosis of this case is multicystic mesothelioma.
There are some cases of low-grade endometrial stromal sarcoma metastatic to the lung in which the lesions were cystic and initially reported as mesenchymal cystic hamartoma, but a history of endometrial stromal sarcoma 27 years earlier was elicited.6
Multicystic Endometrial Stromal Sarcoma
217
Figure 5. Tumor cells demonstrating strong membrane positivity for CD10.
The histologic differential diagnosis in this case includes mainly a cystically degenerated leiomyoma. This tumor has irregularly distributed and thick-walled blood vessels in contrast to the small vessels resembling spiral arterioles of endometrial stromal sarcomas. The cells in leiomyoma are often arranged in interlacing fascicles and have cigarshaped nuclei with fibrillary cytoplasm. Sometimes endometrial stromal sarcoma can show smooth muscle differentiation, and when this feature exceeds 30%, the tumor is classified as a combined stromal-smooth muscle tumor.7 The difference between low-grade endometrial stromal sarcoma and stromal nodule is based on the demonstration of invasion to myomterium and vessels in the former. Stromal nodules can sometimes have finger-like projections into the myometrium, but these projections should not exceeded 2 to 3 mm in depth.8 Adenomatoid tumors have also been reported, presenting as a multicystic uterine mass. Histologically, this lesion is composed of multiple cavities lined by flat cells lying among thin septa of connective tissue.9 Others areas, however, usually display the more typical histologic pattern of adenomatoid tumor such as tubular (adenoid),
angiomatoid, and plexiform (solid) pattern. Immunohistochemical markers in these tumors are positive for calretinin, cytokeratin, and vimentin and are usually negative for CD10. For pelvic masses that can be assessed by ultrasound, the differential diagnosis is very extensive. The size, morphology, and the echogenicity of the mass is very important for the proper interpretation of the lesion.10 The majority of the cystic pelvic masses localized in the adnexa are physiologic ovarian cysts or retention cysts like follicular, luteinized, or epithelial surface cysts, but there are other nonphysiologic adnexal masses that should be taken into consideration in the radiologic differential diagnosis (Table 1). Cystic endometrial stromal sarcoma should also be added in the differential diagnosis of cystic uterine tumors. References 1. Silverbeg SG, Kurman RJ: Tumors of the uterine corpus and gestational trophoblastic disease. In: Atlas of Tumor Pathology. Third Series. Fascicle 3. Washington, DC, Armed Forces Institute of Pathology, 1992 2. Aaro LA, Symmonds RE, Dockerty MB: Sarcoma of the Uterus. A clinical and pathologic study of 177 cases. Am J Obstet Gynecol 1966;94:101-109 3. Clement PB, Young RH: Florid cystic endosalpingiosis
218
Pe´ rez-Montiel, Sameron, and Malagon
with tumor like manifestations report of four cases including the first reported cases of transmural endosalpingiosis of the uterus. Am J Surg Pathol 1999;23:166-175 4. Troiano RN, Flynn SD, McCarthy S: Cystic adenomyosis of the uterus. J Magn Reson Imaging 1998;8:1198-1202 5. Gemer O, Mor C, Segal S: Uterine adenofibroma presenting as a cystic adnexal mass. Arch Gynecol Obstet 1995;256:99101 6. Abrams J, Talcott J, Corson JM: Pulmonary metastasis in patients with low-grade endometrial stroma sarcoma. Am J Surg Pathol 1989;13:133-140 7. Oliva E, Clement PB, Young RH, et al: Mixed endometrial
stromal and smooth muscle tumors of the uterus a clinicopathologic study, 15 cases. Am J Surg Pathol 1998;22:997-1005 8. Tavassoli FA, Norris HJ: Mesenchymal tumours of the uterus. VII. A clinicopathological study of 60 endometrial stromal nodules. Histopathology 1981;5:1-10 9. Palacios J, Sua´ rez Manrique A, Ruiz Villaespesa A, et al: Cystic adenomatoid tumors of the uterus. Int J Gynecol Pathol 1991;10:296-301 10. Liebman AJ, Druse B, McSweeney M: Transvaginal sonography: comparison with transabdomial sonography in the diagnosis of pelvic masses. AJR Am J Roentgenol 1993; 52:1849-1856
Multicystic Endometrial Stromal Sarcoma Delia Pe´rez-Montiel, MD, Arturo Albrandt Salmeron, MD, and Hugo Domı´nguez Malagon, MD Endometrial stromal sarcoma usually has the gross appearance of a single nodule, multiple masses, or a poorly demarcated lesion with occasional cystic degeneration; however, a multilocular form has not been described in the literature. We report the case of a 25-year-old woman with a cystic multilocular lesion with thin septae measuring 8 cm, discovered by a pelvic ultrasonography. Grossly, it was a multicystic mass located in uterine fundus that was attached to myometrium and showed infiltrating borders. We propose that cystic endometrial stromal sarcoma should be included in the differential diagnosis of cystic uterine tumors. Ann Diagn Pathol 8: 213-218, 2004. © 2004 Elsevier Inc. All rights reserved. Index Words: Endometrial stromal sarcoma, cystic tumors, uterus
E
NDOMETRIAL stromal sarcoma is a rare tumor that generally presents as a diffuse process involving the uterus. Grossly, this lesion can present as a single nodule, multiple masses, or a poorly demarcated pink, tan, or yellow diffuse thickening of the myometrium without any clear demarcation. Cystic degeneration with hemorrhage can be seen in some cases, but occurrence as a multiloculated cystic mass has not been reported. Clinical History
A 25-year-old woman was admitted for evaluation of pelvic pain and a mass of 2 months’ duration. She had been pregnant four times with normal vaginal deliveries. On physical examination, the patient had a palpable mass in the pelvic region that was mobile and not painful. Laboratory findings included CA125 of 9.0 U/mL (normal range, 0 to 21 U/mL) and ␣-fetoprotein of 1.4 ng/mL (normal range, 0 to 1.85 ng/mL). A simple hysterectomy was performed. Eight months later the patient is well and free of disease.
From the Departments of Surgical Pathology and Diagnostic Radiology, Instituto Nacional de Cancerologia, Mexico City, Mexico. Address reprint requests to Delia Pe´rez–Montiel, MD, Instituto Nacional de Cancerologia, Av San Fernando #22 Col Seccion XVI, Delg Tlalpan, Mexico City 14080. © 2004 Elsevier Inc. All rights reserved. 1092-9134/04/0804-0004$30.00/0 doi:10.1053/j.anndiagpath.2004.04.004
Radiologic Findings An abdominal ultrasonography along the axial level with high resolution in real-time gray scale and Doppler color disclosed a cystic lesion that measured 8.2 ⫻ 6.3 cm with smooth and welldefined borders. The lesion showed septae with variable thickness surrounding anechoic cavities without ecogenic images inside of them (Fig 1). The lesion was attached to the round ligament and it was not possible to determine if it arose from the uterine corpus or ovary. Doppler study showed a lesion with peripheral vascularity without low or high flow inside of the multicystic lesion. The septa were also avascular. Outside the mass the peripheral vascularity was low (Fig 2). The ultrasonographic diagnosis was endometrial cyst versus complex ovarian cyst. Gross Findings At surgery, the ovaries were grossly normal, but the uterine corpus was increased in size with an irregular surface in the fundus. Grossly, the uterine surface was multilobulated and smooth; the cut surface showed an 8 ⫻ 6 ⫻ 6 cm multicystic mass situated in the uterine fundus extending to lateral cornu. This lesion was attached to the myometrium and consisted of multiple cysts containing clear fluid; the cyst walls were thin and tanslucent (Fig 3). The rest of the uterus was grossly normal. Pathologic Findings Microscopically, the cyst walls were surrounded by sheets of small cells of relatively uniform size,
Annals of Diagnostic Pathology, Vol 8, No 4 (August), 2004: pp 213-218
213
214
Pe´ rez-Montiel, Sameron, and Malagon
Figure 1. Abdominal ultrasonography disclosed a cystic lesion with smooth and well-defined borders. Septa of variable thickness are seen surrounding anechoic cavities.
with scant amphophylic cytoplasm (Fig 4). The nuclei were round to ovoid with finely dispersed chromatin. Other areas showed epithelioid cells with ample eosinophilic cytoplasm. There were 1 to 2 mitoses per 10 high power fields. The cystic cavities were devoid of a lining. The tumor showed
Figure 2. Same image as Fig 1 with Doppler study showed a lesion with peripheral vascularity without low or high flow inside the multicystic lesion. Septa were also avascular.
focal invasion of the myometrium by tongues of tumor cells larger than 3 mm. No vascular invasion was identified. Immunohistochemical studies were performed; the tumor cells were reactive for CD10 (DAKO, Carpinteria, CA; monoclonal 1:15), actin (DAKO;
Multicystic Endometrial Stromal Sarcoma
215
Figure 3. Uterine corpus with multicystic mass situated in the uterine fundus.
monoclonal 1:50), and focally for desmin (DAKO, monoclonal 1:100). They were negative for AE1/ AE3 cytokeratin (Biogenics, San Ramon, CA, monoclonal 1:50), S-100 protein (DAKO, polyclonal 1:800) and EMA (DAKO, monoclonal 1:80) (Fig 5). Discussion Endometrial stromal lesions account for less than 10% of the nonepithelial tumors of the uterine corpus.1 In the series from the Mayo Clinic,2 endometrial stromal sarcomas represent 10% of all uterine sarcomas. Age at presentation has shown a wide range, from teenagers to elderly women, but the median age is 39 years. No specific ultrasonographic data has been reported for these tumors. The findings are very similar to that of other mesenchymal or epithelial uterine tumors. The most frequent benign uterine lesions that can present with a cystic image on ultrasonography include degenerated leiomyomas, pyometra, hydrocolpos/hematocolpos, uterus didelphus, adenomyosis, and lipoleyomioma. Malignant uterine neoplasms with an ultrasonographic cystic appearance include endometrial carcinoma, leiomyosarcoma, and trophoblastic invasive disease.
Grossly, endometrial stromal sarcomas are generally solid, soft, and tan to gray. They are generally localized in the myometrium, are well circumscribed, and sometimes have a polypoid component. They frequently exhibit foci of necrosis, hemorrhage, and may also show focally some degree of microscopic cystic degeneration, but the development of a large multicystic mass has not been described previously. Differential diagnosis for this tumor includes lesions with gross degenerative cystic changes such as leiomyoma, endometrial stromal nodules, adenomatoid tumor, epithelial cyst, mucinous metastatic carcinoma, or tumors with cystic areas such as lymphangioma, hydatidiform mole, or teratomas.
Table 1. Nonphysiologic Adnexal Masses Endometrioma Tuboovarian abscess Dermoid cyst Ectopic pregnancy Paraovarian cyst Serous/mucinous cystadenoma Peritoneal inclusion cyst Massive ovarian swelling Hydrosalpynx
216
Pe´ rez-Montiel, Sameron, and Malagon
Figure 4. (A) Septae of the lesion shows uniform short spindle cells without lining. (B) Cystic lesion in relation to the myometrium. The cyst wall contains uniform short spindle cells.
Other lesions that have been reported as cystic or multicystic in the uterus are endosalpingiosis,3 adenomyosis,4 and adenofibroma.5 Another condition that must be considered in the differential diagnosis of this case is multicystic mesothelioma.
There are some cases of low-grade endometrial stromal sarcoma metastatic to the lung in which the lesions were cystic and initially reported as mesenchymal cystic hamartoma, but a history of endometrial stromal sarcoma 27 years earlier was elicited.6
Multicystic Endometrial Stromal Sarcoma
217
Figure 5. Tumor cells demonstrating strong membrane positivity for CD10.
The histologic differential diagnosis in this case includes mainly a cystically degenerated leiomyoma. This tumor has irregularly distributed and thick-walled blood vessels in contrast to the small vessels resembling spiral arterioles of endometrial stromal sarcomas. The cells in leiomyoma are often arranged in interlacing fascicles and have cigarshaped nuclei with fibrillary cytoplasm. Sometimes endometrial stromal sarcoma can show smooth muscle differentiation, and when this feature exceeds 30%, the tumor is classified as a combined stromal-smooth muscle tumor.7 The difference between low-grade endometrial stromal sarcoma and stromal nodule is based on the demonstration of invasion to myomterium and vessels in the former. Stromal nodules can sometimes have finger-like projections into the myometrium, but these projections should not exceeded 2 to 3 mm in depth.8 Adenomatoid tumors have also been reported, presenting as a multicystic uterine mass. Histologically, this lesion is composed of multiple cavities lined by flat cells lying among thin septa of connective tissue.9 Others areas, however, usually display the more typical histologic pattern of adenomatoid tumor such as tubular (adenoid),
angiomatoid, and plexiform (solid) pattern. Immunohistochemical markers in these tumors are positive for calretinin, cytokeratin, and vimentin and are usually negative for CD10. For pelvic masses that can be assessed by ultrasound, the differential diagnosis is very extensive. The size, morphology, and the echogenicity of the mass is very important for the proper interpretation of the lesion.10 The majority of the cystic pelvic masses localized in the adnexa are physiologic ovarian cysts or retention cysts like follicular, luteinized, or epithelial surface cysts, but there are other nonphysiologic adnexal masses that should be taken into consideration in the radiologic differential diagnosis (Table 1). Cystic endometrial stromal sarcoma should also be added in the differential diagnosis of cystic uterine tumors. References 1. Silverbeg SG, Kurman RJ: Tumors of the uterine corpus and gestational trophoblastic disease. In: Atlas of Tumor Pathology. Third Series. Fascicle 3. Washington, DC, Armed Forces Institute of Pathology, 1992 2. Aaro LA, Symmonds RE, Dockerty MB: Sarcoma of the Uterus. A clinical and pathologic study of 177 cases. Am J Obstet Gynecol 1966;94:101-109 3. Clement PB, Young RH: Florid cystic endosalpingiosis
218
Pe´ rez-Montiel, Sameron, and Malagon
with tumor like manifestations report of four cases including the first reported cases of transmural endosalpingiosis of the uterus. Am J Surg Pathol 1999;23:166-175 4. Troiano RN, Flynn SD, McCarthy S: Cystic adenomyosis of the uterus. J Magn Reson Imaging 1998;8:1198-1202 5. Gemer O, Mor C, Segal S: Uterine adenofibroma presenting as a cystic adnexal mass. Arch Gynecol Obstet 1995;256:99101 6. Abrams J, Talcott J, Corson JM: Pulmonary metastasis in patients with low-grade endometrial stroma sarcoma. Am J Surg Pathol 1989;13:133-140 7. Oliva E, Clement PB, Young RH, et al: Mixed endometrial
stromal and smooth muscle tumors of the uterus a clinicopathologic study, 15 cases. Am J Surg Pathol 1998;22:997-1005 8. Tavassoli FA, Norris HJ: Mesenchymal tumours of the uterus. VII. A clinicopathological study of 60 endometrial stromal nodules. Histopathology 1981;5:1-10 9. Palacios J, Sua´ rez Manrique A, Ruiz Villaespesa A, et al: Cystic adenomatoid tumors of the uterus. Int J Gynecol Pathol 1991;10:296-301 10. Liebman AJ, Druse B, McSweeney M: Transvaginal sonography: comparison with transabdomial sonography in the diagnosis of pelvic masses. AJR Am J Roentgenol 1993; 52:1849-1856