International Journal of Gynecological Pathology 34:298–302, Lippincott Williams & Wilkins, Baltimore r 2015 International Society of Gynecological Pathologists
Case Report
Primary Myxoid Liposarcoma of the Ovary in a Postpartum Female: A Case Report and Review of Literature Sharon X. Liang, M.D., Ph.D., Brooke Howitt, M.D., Matthew J. Blitz, M.D., M.B.A., Tamfiqul Bhuiya, M.D., Farnaz Thamasebi, M.D., Jason Sternchos, M.D., and Karin Shih,
M.D.
Summary: A 36-year-old gravida 4, para 2 African-American woman, presented at three months postpartum with a right ovarian mass identified on a lumbar spine MRI as part of a neurology workup for persistent lower back pain. A follow-up pelvic ultrasound noted a 7.0 6.1 3.8 cm septated mixed cystic and solid mass. Exploratory laparoscopy and right ovarian cystectomy yielded a final pathologic diagnosis of intermediate grade myxoid liposarcoma, confirmed with DDIT3 gene rearrangement studies. Key Words: Myxoid liposarcoma—Ovary—DDIT3—FISH.
cell liposarcoma). MLS is characterized by DDIT3 rearrangement at the 12q13.3 locus, resulting in a balanced translocation, either t(12;16)(q13; p11) (Z90% of cases) or t(12;22) (q13;q12) (B5%–10% of cases), producing either DDIT3-FUS or DDIT3EWSR1 fusion transcripts, respectively (12,13). Most patients are between the third and the fifth decade of life, and MLS is the most common liposarcoma in children and young adults. The prognosis is dependent upon the grade, which is determined by the tumor cellularity. Unlike other sarcomas, MLS has a high prevalence of extrapulmonary metastasis. The bones and soft tissues are the most common site of involvement, followed by the lungs and liver (14). Ovarian involvement was reported in 1 case (15). The 10-yr distant metastases-free survival is about 86% (16). We now report the second case of a primary ovarian MLS in a 36-yr-old postpartum African American woman. Fluorescence in situ hybridization (FISH) for DDIT3 (formerly called CHOP) gene rearrangement was performed on the tumor to confirm the diagnosis.
Primary soft-tissue-type sarcoma of the ovary is uncommon, and most reports in literature are either in the format of single case report or a small case series. Fibrosarcoma is the most common type (1,2), followed by leiomyosarcoma (including the myxoid variant) (3,4). Other rare histologic types that have been reported include malignant schwannomas (5), angiosarcomas (6), rhabdomyosarcomas (7), osteosarcomas (8), and chondrosarcomas (9). Recently, Tirabosco et al. (10) reported 1 case of myxoid liposarcoma (MLS) of the ovary in a young girl. MLS accounts for about 30% to 35% of all liposarcomas and is commonly seen in the deep soft tissue of the limbs, particularly the thigh and the popliteal region (11). It comprises a spectrum of tumors, ranging from ‘‘conventional’’ hypocellular, low-grade MLS with prominent myxoid stroma, to hypercellular, high-grade MLS (formerly called round
From the Departments of Pathology and Laboratory Medicine (S.X.L., T.B., F.T.); Obstetrics and Gynecology (M.J.B., J.S.); Gynecologic Oncology (K.S.), Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York; and Department of Pathology (B.H.), Brigham and Women’s Hospital, Boston, Massachusetts. The authors declare no conflict of interest. Address correspondence and reprint requests to Sharon X. Liang, MD, PhD, Department of Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School of Medicine, 6 Ohio Drive, Suite 202, Lake Success, NY 11042. E-mail: [email protected].
DOI: 10.1097/PGP.0000000000000145
MATERIALS AND METHODS Case History The patient is a 36-yr-old African American woman, gravida 4, para 2, 3 mo status postterm repeat cesarean 298
PRIMARY MYXOID LIPOSARCOMA OF THE OVARY section. Her prenatal course was complicated by a right lower extremity deep vein thrombosis, which was treated with enoxaparin. Her delivery was uncomplicated and she was discharged home on postpartum day 4. In the early postpartum course, she began complaining of persistent right-sided abdominal and lower back pain, prompting a neurology referral. Outpatient magnetic resonance imaging of the lumbar spine performed at 3 mo postpartum demonstrated a right-sided heterogeneous pelvic mass. Follow-up pelvic ultrasound noted a 7.0 6.1 3.8 cm septated mixed cystic and solid mass in the right ovary suggestive of an endometrioma. The left ovary and the uterus were unremarkable. Tumor markers were within normal limits with a carcinoembryonic antigen of 0.2 ng/mL, a-fetoprotein of 2.1 ng/ mL, cancer antigen 125 of 17 U/mL, lactate dehydrogenase of 155 U/L, and a negative quantitative b-human chorionic gonadotropin. Her gynecologic and past medical history was unremarkable. Past surgical history included an appendectomy, cholecystectomy, 2 cesarean sections, and right knee arthroscopy (benign finding with cartilage loss). At 4 mo postpartum, she was taken to the operating room for exploratory laparoscopy and right ovarian cystectomy. Following the pathologic diagnosis of MLS in the right ovary, she was further evaluated with computed tomography scans of the chest, abdomen, and pelvis with no evidence of disease. Mammogram and breast ultrasound were negative for suspicious lesions. A second surgical intervention for laparoscopic right salpingo-oophorectomy was performed, which was negative for tumor. No adjuvant radiotherapy or chemotherapy was given. At 8-mo follow-up, the patient is well with no evidence of disease. Histology and Immunohistochemistry Tissue sections were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned at 4-mm thickness, and stained with hematoxylin and eosin. The immunohistochemistry was performed at Immunopathology Laboratory at Long Island Jewish Medical Center (North Shore-LIJ Health System, New Hyde Park, NY), where the Ventana BenchMark Autostainer (Ventana Medical System, Tucson, AZ) was used on 4-mm-thick formalin-fixed and deparaffinized sections with the following markers: AE1/AE3, EMA, Ki-67, S-100, SMA, desmin, CD10, CD31, CD34 (QBEND-10), CD68, inhibin, calretinin, and CD117. FISH DDIT3 rearrangement studies were performed at the Cytogenetics Laboratory of Brigham and
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Women’s Hospital (Boston, MA). Scrolls 50 mm each of formalin-fixed paraffin-embedded tumor sections were interrogated with the LSI DDIT3 Dual Color, Break Apart Rearrangement Probe at 12q13 (Abbott Molecular, Des Plaines, IL), according to manufacture instructions. Slides were analyzed with the Olympus fluorescent microscope. Signals were counted in 50 intact and nonoverlapping interphase nuclei in at least 3 different microscopic fields. RESULTS Grossly, the tumor was a multiloculated complex cyst measuring 5 4 1.5 cm, with a smooth outer surface. The cysts contained abundant light yellow gelatinous substance, some of which was attached to the inner surface creating a multinodular appearance. The cyst wall thickness varied from 0.1 to 0.6 cm. Normal ovarian parenchyma was not identified grossly. The mass was entirely submitted and processed for microscopic examination. Histologic examination of the tumor at low power revealed a lobulated, multinodular pattern of growth. The tumor was moderately cellular with fusiform, stellate, and spindle cells set in a myxoid matrix (Figs. 1A, B). Mitotic figures were not identified. There were many thin-walled branching vascular channels throughout, exhibiting the characteristic ‘‘chicken-wire’’ appearance (Figs. 1A, B). Extracellular mucin formed prominent mucin pools and microcystic change (Fig. 1C). Scattered small, mainly univacuolated, lipoblasts were identified at multiple foci (Fig. 1D). A rim of very attenuated ovarian cortical stroma at the periphery of the tumor was identified focally. Given the slightly increased cellularity, the tumor was considered intermediate grade. Immunohistochemistry showed that the lesional cells were faintly positive for S-100, CD117, CD68, and CD10; and were negative for AE1/AE3, EMA, SMA, desmin, inhibin, calretinin, CD31, and CD34. The ki-67 proliferation index was approximately 5%. FISH studies showed the presence of split red and green signals in 42/50 nuclei, indicating DDIT3 rearrangement (Fig. 2). DISCUSSION We report the second confirmed case of primary ovarian MLS. Primary sarcoma of the ovary is extremely rare, and most reports in the literature are small case series or single case reports. Metastasis from a soft-tissue primary is more common than Int J Gynecol Pathol Vol. 34, No. 3, May 2015
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A
B
C
D
FIG. 1. Microscopic appearance of the tumor. (A) Low-power view showing a spindle cell tumor set in a myxoid matrix with many thinwalled branching vascular channels throughout, exhibiting the characteristic ‘‘chicken-wire’’ appearance. (B) The tumor was moderately cellular with fusiform, stellate, and spindle cells. (C) Extracellular mucin formed prominent mucin pools and microcystic change. (D) Small univacuolated lipoblasts were identified.
FIG. 2. Fluorescence in situ hybridization studies showing the presence of split red [50 (C)] and green [30 (T)] signals, indicating DDIT3 rearrangement. C and T refer to centrosome and telomere portion of the probe, respectively.
Int J Gynecol Pathol Vol. 34, No. 3, May 2015
primary ovarian soft-tissue sarcoma. Among primary ovarian sarcomas, fibrosarcoma is the most common type (1,2), followed by leiomyosarcoma (3,4). However fibrosarcoma of the ovary is typically considered to be an ovarian-specific diagnosis, at the malignant end of ovarian fibromatous/fibroblastic neoplasms, rather than an unusual presentation of a classic soft-tissue sarcoma. Likewise, leiomyosarcoma is the most common malignant mesenchymal tumor of the female genital tract, although it much more frequently arises in the uterine corpus than ovary. Other sarcomas previously reported as primarily arising in the ovary include malignant schwannoma (5), angiosarcoma (6), rhabdomyosarcoma (7), osteosarcoma (8), and chondrosarcoma (9). In the current report, pathologic examination of the complex solid and cystic mass demonstrated a myxoid spindle cell neoplasm with features suggestive of a soft-tissue MLS. Because of its unusual location,
PRIMARY MYXOID LIPOSARCOMA OF THE OVARY we sought the expert opinion of Dr Christopher Fletcher at Brigham and Women’s Hospital. His histologic assessment, supported by a positive cytogenetic test demonstrating DDIT3 gene rearrangement, confirmed the diagnosis of MLS, intermediate grade. Further imaging and clinical work-up, with subsequent right salpingo-oophorectomy revealed no residual tumor and no evidence of disease outside or inside the pelvis. The patient was doing well at an 8-mo follow-up visit. Given the truly exceptional anatomic location of this tumor, the possibility of spread from a soft-tissue site was considered. The most common anatomic sites for MLS include the lower limb and buttock, most commonly the thigh (17), but MLS has also been reported in the retroperitoneum, head, and neck, and very rarely, visceral organs although not all of these reports had molecular/genetic confirmatory studies (18–21). It is unlikely that our patient had metastatic MLS given the extensive clinical and radiologic investigation did not find any tumors inside or outside the pelvis. Furthermore, the tumor was wellcircumscribed and was confined to 1 ovary without any surface involvement. Metastatic MLS from soft-tissue sites to the ovary has been rarely reported (15) and although retroperitoneal liposarcoma mimicking an ovarian mass has been reported (22), actual ovarian involvement in this patient was not documented. When considering a myxoid neoplasm occurring in the ovary, the histologic differential diagnosis is rather limited and includes ovarian myxoma, sex-cord stromal tumors, germ cell tumors, myxoid leiomyosarcoma, low-grade fibromyxoid sarcoma, and biphasic tumors with mesenchymal overgrown. Ovarian myxoma is a benign neoplasm that is paucicellular and lacks nuclear atypia, pseudolipoblasts, and the arborizing vasculature that are characteristic of MLS. Sexcord stromal tumors, especially sclerosing stromal tumor (SST), are also in the differential diagnosis given the common presence of cystic degeneration. SST has a characteristic pseudolobular pattern with alternating hypercellular and hypocellular nodules of spindled fibroblasts and plump lutein cells and densely collagenous or edematous stroma. The prominent vasculature of SST has a hemangiopericytoma-like appearance, in contrast to the chicken-wire vessels of MLS. Other sex-cord stromal tumors, including fibroma, can also have extensive edematous change. In addition, sex-cord stromal tumors are typically immunoreactive for inhibin and/or calretinin, whereas MLS is not. A rare ovarian sex-cord stromal tumor is the signet-ring cell stromal tumor, which can mimic
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the pseudolipoblasts of MLS, although to our knowledge signet-ring cell stromal tumors have not been interrogated for DDIT3 rearrangement. Germ cell tumors, particularly yolk sac tumor but also immature teratoma, often have a myxoid and edematous background and the cells can occasionally be quite bland in appearance. Immunohistochemistry can be helpful in this distinction, as germ cell tumors are positive for SALL4, and yolk sac tumors will often be immunoreactive for a-fetoprotein and/or glypican3. Myxoid leiomyosarcoma would show at least focal fascicular architecture, and is immunoreactive for smooth muscle markers. Low-grade fibromyxoid sarcoma is another soft-tissue sarcoma that can (uncommonly) occur within the pelvic cavity, may involve ovary (23) and consists of uniform fibroblastic-like spindle cells with sharp transitions between collagenized and myxoid stroma. A biphasic tumor-like carcinosarcoma or adenosarcoma with mesenchymal overgrown can be confirmed by extensive sampling to find any epithelial component. To date no diagnostic immunohistochemical markers for MLS have been reported, although S-100 positivity is usually positive (24), as in our reported case. Importantly, none of the entities in the differential diagnosis have demonstrated the DDIT3 gene rearrangement, which is seen in the majority of MLS. Only 1 case of ovarian MLS has been reported previously in the literature (10), and it bears many similarities to the case that we describe. Both patients were African American. Both presented with abdominopelvic pain, and the ovarian mass was identified on magnetic resonance imaging. Both tumors displayed classic histologic features of MLS, with confirmatory DDIT3 (CHOP) rearrangement identified by FISH studies. The first case was in an adolescent girl, whereas our patient was a postpartum multiparous female. Both patients were free of disease at the time of limited follow-up (8 mo and 10 mo), however, the prognosis of primary ovarian MLS remains to be seen as late recurrences/metastases are common in soft-tissue MLS. In summary, we report the second case of a primary ovarian MLS, in a 36-yr-old African American who presented during the postpartum period with abdominal and lower back pain. The histologic diagnosis was confirmed by FISH studies demonstrating the DDIT3 rearrangement. ACKNOWLEDGMENT: The authors thank Dr Christopher Fletcher of the Department of Pathology of Brigham and Women’s Hospital, Boston, MA who kindly offered his valuable opinion and confirmed the diagnosis. Int J Gynecol Pathol Vol. 34, No. 3, May 2015
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1. Prat J, Scully RE. Cellular fibromas and fibrosarcomas of the ovary: a comprehensive clinicopathologic analysis of seventeen cases. Cancer 1981;47:2663–70. 2. Kraemer BB, Silva EG, Sneige N. Fibrosarcoma of the ovary. A new component in the nevoid basal-cell carcinoma syndrome. Am J Surg Pathol 1984;8:231–6. 3. Lerwill MJ, Sung R, Oliva E, et al. Smooth muscle tumors of the ovary. A clinicopathological study of 54 cases emphasizing prognostic criteria, histologic variants and the differential diagnosis. Am J Surg Pathol 2004;28:1426–51. 4. Nogales FF, Ayala A, Ruiz-Avila I, et al. Myxoid leiomyosaroma of the ovary: analysis of three cases. Human Pathol 1991;22:1268–73. 5. Stone GC, Bell DA, Fuller A, et al. Malignant schwannoma of the ovary. Report of a case. Cancer 1986;58:1575–82. 6. Nielsen GP, Young RH, Prat J, et al. Primary angiosarcoma of ovary: a report of seven cases and a review of the literature. Int J Gynecol Pathol 1997;16:378–82. 7. Nielsen GP, Oliva E, Young RH, et al. Primary ovarian rhabdomyosarcoma: a report of 13 cases. Int. J Gynecol Pathol 1998;17:113–9. 8. Fadare O, Bossuyt V, Martel M, et al. Primary osteosarcoma of the ovary: case report and literature review. Int J Gynecol Pathol 2007;26:21–5. 9. Talerman A, Auerbach WM, Van Meurs AJ. Primary chondrosarcoma of the ovary. Histopathology 1981;5:319–24. 10. Tirabosco R, Arora R, Ye H, et al. Primary myxoid liposarcoma of the ovary in an adolescent girl: a case report. Int J Gynecol Pathol 2010;29:256–9. 11. Orvieto E, Furlanetto A, Laurino L, et al. Myxoid and round cell liposarcoma: a spectrum of myxoid adipocytic neoplasia. Semin Diagn Pathol 2001;18:267–73. 12. Tanas MR, Goldblum JR. Fluorescence in situ hybridization in the diagnosis of soft tissue neoplasms: a review. Adv Anat Pathol 2009;16:383–91.
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13. Downs-Kelly E, Goldblum JR, Patel RM, et al. The utility of fluorescence in situ hybridization (FISH) in the diagnosis of myxoid soft tissue neoplasms. Am J Surg Pathol 2008;32: 8–13. 14. Sheah K, Ouellette HA, Torriani M, et al. Metastatic myxoid liposarcomas: imaging and histopathologic findings. Skeletal Radiol 2008;37:251–8. 15. Rodeck CH, Pryse-Davies J, Malvern J, et al. Secondary liposarcoma of the ovary. Int J Gynecol Obstet 1977;15:38–40. 16. Fuglø HM, Maretty-Nielsen K, Hovgaard D, et al. Metastatic pattern, local relapse, and survival of patients with myxoid liposarcoma: a retrospective study of 45 patients. Sarcoma 2013;Article ID:548628. 17. Weiss SW, Goldblum JR. Myxoid liposarcoma. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss’s Soft Tissue Tumors.; 5th ed. New York: Mosby Elsevier; 2008:498–510. 18. Lee SY, Goh BK, Teo MC, et al. Retroperitoneal liposarcomas: the experience of a tertiary Asian center. World J Surg Oncol 2011;1:9–12. 19. Fernandez-Ruiz M, Rodriguez-Gil Y, Guerra-Vales JM, et al. Primary retroperitoneal liposarcoma: clinical and histological analysis of ten cases. Gastroenterol Hepatol 2010;33:370–6. 20. Gritli S, Khamassi K, Lachkhem A, et al. Head and neck liposarcomas: a 32 years experience. Auris Nasus Larynx 2010;37:347–51. 21. Gutsu E, Ghidirim G, Gagauz I, et al. Liposarcoma of the colon: a case report and review of literature. J Gastrointest Surg 2006;10:652–6. 22. Hsiao JC, Yang YC, Lin WC, et al. Primary retroperitoneal liposarcoma mimicking ovarian cancer: a case report. Zhonghua Yi Xue Za Zhi 1988;61:295–300. 23. Winfield HL, De Las Casas LE, Greenfield WW, et al. Low-grade fibromyxoid sarcoma presenting clinically as a primary ovarian neoplasm: a case report. Int J Gynecol Pathol 2007;26:173–6. 24. Lopez-Gines C, Navarro S, Pevdro-Olava A, et al. Malignant myxoid liposarcoma: an immunohistochemical, electron-microscopical and cytogenetical analysis. Appl Pathol 1989;7:285–93.
Case Report
Primary Myxoid Liposarcoma of the Ovary in a Postpartum Female: A Case Report and Review of Literature Sharon X. Liang, M.D., Ph.D., Brooke Howitt, M.D., Matthew J. Blitz, M.D., M.B.A., Tamfiqul Bhuiya, M.D., Farnaz Thamasebi, M.D., Jason Sternchos, M.D., and Karin Shih,
M.D.
Summary: A 36-year-old gravida 4, para 2 African-American woman, presented at three months postpartum with a right ovarian mass identified on a lumbar spine MRI as part of a neurology workup for persistent lower back pain. A follow-up pelvic ultrasound noted a 7.0 6.1 3.8 cm septated mixed cystic and solid mass. Exploratory laparoscopy and right ovarian cystectomy yielded a final pathologic diagnosis of intermediate grade myxoid liposarcoma, confirmed with DDIT3 gene rearrangement studies. Key Words: Myxoid liposarcoma—Ovary—DDIT3—FISH.
cell liposarcoma). MLS is characterized by DDIT3 rearrangement at the 12q13.3 locus, resulting in a balanced translocation, either t(12;16)(q13; p11) (Z90% of cases) or t(12;22) (q13;q12) (B5%–10% of cases), producing either DDIT3-FUS or DDIT3EWSR1 fusion transcripts, respectively (12,13). Most patients are between the third and the fifth decade of life, and MLS is the most common liposarcoma in children and young adults. The prognosis is dependent upon the grade, which is determined by the tumor cellularity. Unlike other sarcomas, MLS has a high prevalence of extrapulmonary metastasis. The bones and soft tissues are the most common site of involvement, followed by the lungs and liver (14). Ovarian involvement was reported in 1 case (15). The 10-yr distant metastases-free survival is about 86% (16). We now report the second case of a primary ovarian MLS in a 36-yr-old postpartum African American woman. Fluorescence in situ hybridization (FISH) for DDIT3 (formerly called CHOP) gene rearrangement was performed on the tumor to confirm the diagnosis.
Primary soft-tissue-type sarcoma of the ovary is uncommon, and most reports in literature are either in the format of single case report or a small case series. Fibrosarcoma is the most common type (1,2), followed by leiomyosarcoma (including the myxoid variant) (3,4). Other rare histologic types that have been reported include malignant schwannomas (5), angiosarcomas (6), rhabdomyosarcomas (7), osteosarcomas (8), and chondrosarcomas (9). Recently, Tirabosco et al. (10) reported 1 case of myxoid liposarcoma (MLS) of the ovary in a young girl. MLS accounts for about 30% to 35% of all liposarcomas and is commonly seen in the deep soft tissue of the limbs, particularly the thigh and the popliteal region (11). It comprises a spectrum of tumors, ranging from ‘‘conventional’’ hypocellular, low-grade MLS with prominent myxoid stroma, to hypercellular, high-grade MLS (formerly called round
From the Departments of Pathology and Laboratory Medicine (S.X.L., T.B., F.T.); Obstetrics and Gynecology (M.J.B., J.S.); Gynecologic Oncology (K.S.), Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York; and Department of Pathology (B.H.), Brigham and Women’s Hospital, Boston, Massachusetts. The authors declare no conflict of interest. Address correspondence and reprint requests to Sharon X. Liang, MD, PhD, Department of Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School of Medicine, 6 Ohio Drive, Suite 202, Lake Success, NY 11042. E-mail: [email protected].
DOI: 10.1097/PGP.0000000000000145
MATERIALS AND METHODS Case History The patient is a 36-yr-old African American woman, gravida 4, para 2, 3 mo status postterm repeat cesarean 298
PRIMARY MYXOID LIPOSARCOMA OF THE OVARY section. Her prenatal course was complicated by a right lower extremity deep vein thrombosis, which was treated with enoxaparin. Her delivery was uncomplicated and she was discharged home on postpartum day 4. In the early postpartum course, she began complaining of persistent right-sided abdominal and lower back pain, prompting a neurology referral. Outpatient magnetic resonance imaging of the lumbar spine performed at 3 mo postpartum demonstrated a right-sided heterogeneous pelvic mass. Follow-up pelvic ultrasound noted a 7.0 6.1 3.8 cm septated mixed cystic and solid mass in the right ovary suggestive of an endometrioma. The left ovary and the uterus were unremarkable. Tumor markers were within normal limits with a carcinoembryonic antigen of 0.2 ng/mL, a-fetoprotein of 2.1 ng/ mL, cancer antigen 125 of 17 U/mL, lactate dehydrogenase of 155 U/L, and a negative quantitative b-human chorionic gonadotropin. Her gynecologic and past medical history was unremarkable. Past surgical history included an appendectomy, cholecystectomy, 2 cesarean sections, and right knee arthroscopy (benign finding with cartilage loss). At 4 mo postpartum, she was taken to the operating room for exploratory laparoscopy and right ovarian cystectomy. Following the pathologic diagnosis of MLS in the right ovary, she was further evaluated with computed tomography scans of the chest, abdomen, and pelvis with no evidence of disease. Mammogram and breast ultrasound were negative for suspicious lesions. A second surgical intervention for laparoscopic right salpingo-oophorectomy was performed, which was negative for tumor. No adjuvant radiotherapy or chemotherapy was given. At 8-mo follow-up, the patient is well with no evidence of disease. Histology and Immunohistochemistry Tissue sections were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned at 4-mm thickness, and stained with hematoxylin and eosin. The immunohistochemistry was performed at Immunopathology Laboratory at Long Island Jewish Medical Center (North Shore-LIJ Health System, New Hyde Park, NY), where the Ventana BenchMark Autostainer (Ventana Medical System, Tucson, AZ) was used on 4-mm-thick formalin-fixed and deparaffinized sections with the following markers: AE1/AE3, EMA, Ki-67, S-100, SMA, desmin, CD10, CD31, CD34 (QBEND-10), CD68, inhibin, calretinin, and CD117. FISH DDIT3 rearrangement studies were performed at the Cytogenetics Laboratory of Brigham and
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Women’s Hospital (Boston, MA). Scrolls 50 mm each of formalin-fixed paraffin-embedded tumor sections were interrogated with the LSI DDIT3 Dual Color, Break Apart Rearrangement Probe at 12q13 (Abbott Molecular, Des Plaines, IL), according to manufacture instructions. Slides were analyzed with the Olympus fluorescent microscope. Signals were counted in 50 intact and nonoverlapping interphase nuclei in at least 3 different microscopic fields. RESULTS Grossly, the tumor was a multiloculated complex cyst measuring 5 4 1.5 cm, with a smooth outer surface. The cysts contained abundant light yellow gelatinous substance, some of which was attached to the inner surface creating a multinodular appearance. The cyst wall thickness varied from 0.1 to 0.6 cm. Normal ovarian parenchyma was not identified grossly. The mass was entirely submitted and processed for microscopic examination. Histologic examination of the tumor at low power revealed a lobulated, multinodular pattern of growth. The tumor was moderately cellular with fusiform, stellate, and spindle cells set in a myxoid matrix (Figs. 1A, B). Mitotic figures were not identified. There were many thin-walled branching vascular channels throughout, exhibiting the characteristic ‘‘chicken-wire’’ appearance (Figs. 1A, B). Extracellular mucin formed prominent mucin pools and microcystic change (Fig. 1C). Scattered small, mainly univacuolated, lipoblasts were identified at multiple foci (Fig. 1D). A rim of very attenuated ovarian cortical stroma at the periphery of the tumor was identified focally. Given the slightly increased cellularity, the tumor was considered intermediate grade. Immunohistochemistry showed that the lesional cells were faintly positive for S-100, CD117, CD68, and CD10; and were negative for AE1/AE3, EMA, SMA, desmin, inhibin, calretinin, CD31, and CD34. The ki-67 proliferation index was approximately 5%. FISH studies showed the presence of split red and green signals in 42/50 nuclei, indicating DDIT3 rearrangement (Fig. 2). DISCUSSION We report the second confirmed case of primary ovarian MLS. Primary sarcoma of the ovary is extremely rare, and most reports in the literature are small case series or single case reports. Metastasis from a soft-tissue primary is more common than Int J Gynecol Pathol Vol. 34, No. 3, May 2015
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A
B
C
D
FIG. 1. Microscopic appearance of the tumor. (A) Low-power view showing a spindle cell tumor set in a myxoid matrix with many thinwalled branching vascular channels throughout, exhibiting the characteristic ‘‘chicken-wire’’ appearance. (B) The tumor was moderately cellular with fusiform, stellate, and spindle cells. (C) Extracellular mucin formed prominent mucin pools and microcystic change. (D) Small univacuolated lipoblasts were identified.
FIG. 2. Fluorescence in situ hybridization studies showing the presence of split red [50 (C)] and green [30 (T)] signals, indicating DDIT3 rearrangement. C and T refer to centrosome and telomere portion of the probe, respectively.
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primary ovarian soft-tissue sarcoma. Among primary ovarian sarcomas, fibrosarcoma is the most common type (1,2), followed by leiomyosarcoma (3,4). However fibrosarcoma of the ovary is typically considered to be an ovarian-specific diagnosis, at the malignant end of ovarian fibromatous/fibroblastic neoplasms, rather than an unusual presentation of a classic soft-tissue sarcoma. Likewise, leiomyosarcoma is the most common malignant mesenchymal tumor of the female genital tract, although it much more frequently arises in the uterine corpus than ovary. Other sarcomas previously reported as primarily arising in the ovary include malignant schwannoma (5), angiosarcoma (6), rhabdomyosarcoma (7), osteosarcoma (8), and chondrosarcoma (9). In the current report, pathologic examination of the complex solid and cystic mass demonstrated a myxoid spindle cell neoplasm with features suggestive of a soft-tissue MLS. Because of its unusual location,
PRIMARY MYXOID LIPOSARCOMA OF THE OVARY we sought the expert opinion of Dr Christopher Fletcher at Brigham and Women’s Hospital. His histologic assessment, supported by a positive cytogenetic test demonstrating DDIT3 gene rearrangement, confirmed the diagnosis of MLS, intermediate grade. Further imaging and clinical work-up, with subsequent right salpingo-oophorectomy revealed no residual tumor and no evidence of disease outside or inside the pelvis. The patient was doing well at an 8-mo follow-up visit. Given the truly exceptional anatomic location of this tumor, the possibility of spread from a soft-tissue site was considered. The most common anatomic sites for MLS include the lower limb and buttock, most commonly the thigh (17), but MLS has also been reported in the retroperitoneum, head, and neck, and very rarely, visceral organs although not all of these reports had molecular/genetic confirmatory studies (18–21). It is unlikely that our patient had metastatic MLS given the extensive clinical and radiologic investigation did not find any tumors inside or outside the pelvis. Furthermore, the tumor was wellcircumscribed and was confined to 1 ovary without any surface involvement. Metastatic MLS from soft-tissue sites to the ovary has been rarely reported (15) and although retroperitoneal liposarcoma mimicking an ovarian mass has been reported (22), actual ovarian involvement in this patient was not documented. When considering a myxoid neoplasm occurring in the ovary, the histologic differential diagnosis is rather limited and includes ovarian myxoma, sex-cord stromal tumors, germ cell tumors, myxoid leiomyosarcoma, low-grade fibromyxoid sarcoma, and biphasic tumors with mesenchymal overgrown. Ovarian myxoma is a benign neoplasm that is paucicellular and lacks nuclear atypia, pseudolipoblasts, and the arborizing vasculature that are characteristic of MLS. Sexcord stromal tumors, especially sclerosing stromal tumor (SST), are also in the differential diagnosis given the common presence of cystic degeneration. SST has a characteristic pseudolobular pattern with alternating hypercellular and hypocellular nodules of spindled fibroblasts and plump lutein cells and densely collagenous or edematous stroma. The prominent vasculature of SST has a hemangiopericytoma-like appearance, in contrast to the chicken-wire vessels of MLS. Other sex-cord stromal tumors, including fibroma, can also have extensive edematous change. In addition, sex-cord stromal tumors are typically immunoreactive for inhibin and/or calretinin, whereas MLS is not. A rare ovarian sex-cord stromal tumor is the signet-ring cell stromal tumor, which can mimic
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the pseudolipoblasts of MLS, although to our knowledge signet-ring cell stromal tumors have not been interrogated for DDIT3 rearrangement. Germ cell tumors, particularly yolk sac tumor but also immature teratoma, often have a myxoid and edematous background and the cells can occasionally be quite bland in appearance. Immunohistochemistry can be helpful in this distinction, as germ cell tumors are positive for SALL4, and yolk sac tumors will often be immunoreactive for a-fetoprotein and/or glypican3. Myxoid leiomyosarcoma would show at least focal fascicular architecture, and is immunoreactive for smooth muscle markers. Low-grade fibromyxoid sarcoma is another soft-tissue sarcoma that can (uncommonly) occur within the pelvic cavity, may involve ovary (23) and consists of uniform fibroblastic-like spindle cells with sharp transitions between collagenized and myxoid stroma. A biphasic tumor-like carcinosarcoma or adenosarcoma with mesenchymal overgrown can be confirmed by extensive sampling to find any epithelial component. To date no diagnostic immunohistochemical markers for MLS have been reported, although S-100 positivity is usually positive (24), as in our reported case. Importantly, none of the entities in the differential diagnosis have demonstrated the DDIT3 gene rearrangement, which is seen in the majority of MLS. Only 1 case of ovarian MLS has been reported previously in the literature (10), and it bears many similarities to the case that we describe. Both patients were African American. Both presented with abdominopelvic pain, and the ovarian mass was identified on magnetic resonance imaging. Both tumors displayed classic histologic features of MLS, with confirmatory DDIT3 (CHOP) rearrangement identified by FISH studies. The first case was in an adolescent girl, whereas our patient was a postpartum multiparous female. Both patients were free of disease at the time of limited follow-up (8 mo and 10 mo), however, the prognosis of primary ovarian MLS remains to be seen as late recurrences/metastases are common in soft-tissue MLS. In summary, we report the second case of a primary ovarian MLS, in a 36-yr-old African American who presented during the postpartum period with abdominal and lower back pain. The histologic diagnosis was confirmed by FISH studies demonstrating the DDIT3 rearrangement. ACKNOWLEDGMENT: The authors thank Dr Christopher Fletcher of the Department of Pathology of Brigham and Women’s Hospital, Boston, MA who kindly offered his valuable opinion and confirmed the diagnosis. Int J Gynecol Pathol Vol. 34, No. 3, May 2015
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