International Journal of Gynecological Pathology 35:30–32, Lippincott Williams & Wilkins, Baltimore r 2015 International Society of Gynecological Pathologists
Case Report
Uterine Leiomyoma With Osteoclast-like Giant Cells Marie-Christine Guilbert,
M.D.,
Vanessa Samoue¨lian,
M.D., Ph.D.,
and Kurosh Rahimi,
M.D.
Summary: Numerous histologic variants of uterine leiomyomas have been described. The main interest in recognizing these variants is differentiating them from leiomyosarcoma. Osteoclast-like giant cells (OLGC) have been described in association with leiomyosarcoma but to our knowledge, never with leiomyoma. We here report the case of a 58-year-old woman who underwent an elective total hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy for endometrial atypical complex hyperplasia. Multiple typical uterine leiomyoma were identified. One of them showed numerous OLGC admixed with fascicules of bland smooth muscle cells. No atypical features were identified in multiple sections of this otherwise classic uterine leiomyoma. The OLGC showed strong positivity for CD68. The patient, on follow-up, did not show any evidence of recurrent or metastatic disease. This unusual finding expands the morphologic spectrum of uterine leiomyomas. When confronted with a uterine smooth muscle cell tumor with an OLGC component, it is important to search for atypical features diagnostic of leiomyosarcoma. Key Words: Uterine leiomyoma— Osteoclast-like giant cells—Uterine leiomyosarcoma.
foci suspicious for endometrioid adenocarcinoma Grade 1. The preoperative magnetic resonance imaging showed a thickened endometrium and multiple uterine leiomyomas. The patient underwent an elective total hysterectomy with bilateral salpingooophorectomy and bilateral pelvic lymphadenectomy by robotic surgery. A hysterectomy specimen weighting 183 was received in pathology. There were multiple intramural white, fasciculated nodules, measuring between 0.8 and 6 cm in diameter. No necrosis or hemorrhagic areas were identified. The cervix, fallopian tubes, and ovaries were unremarkable. Histologic examination of the specimen revealed complex hyperplasia with atypia and multiple uterine leiomyomas, characterized by a bland uniform spindle cell proliferation arranged in interlacing fascicules. One of the leiomyomas, measuring 3.5 cm, showed in addition numerous benign-appearing OLGCs that were intimately admixed with the smooth muscle bundles (Figs. 1, 2). There were no mitosis, no necrosis, and no significant cellular atypia. Immunohistochemically, the spindled cells showed strong positivity for
Leiomyomas are the most common tumor of the uterus. They can take on a variety of morphologic aspects, making their differentiation from their malignant counterpart, leiomyosarcoma, sometimes challenging. Osteoclast-like giant cells (OLGC) are rarely seen in the uterus. They have predominantly been described in association with leiomyosarcoma. Here we report a case of a uterine leiomyoma with a significant OLGC component.
CASE REPORT A 58-yr-old woman presented with an 8 month history of postmenopausal bleeding. Endometrial biopsy showed complex hyperplasia with atypia, with From the Department of Pathology (M.-C.G., K.R.); and Division of Gyneco-Oncology (V.S.), Centre hospitalier de l’Universite´ de Montre´al (CHUM), Montre´al, QC, Canada. The authors declare no conflict of interest. Address correspondence and reprint requests to Marie-Christine Guilbert, MD, Department of Pathology, Centre hospitalier universitaire de Montre´al, 1560 rue Sherbrooke Est, Montre´al, QC, Canada H2L 4M1. E-mail: [email protected].
DOI: 10.1097/PGP.0000000000000204
30
Copyright r 2015 International Society of Gynecological Pathologists.
UTERINE LEIOMYOMA WITH OLGCS
31
FIG. 1. Lobular architecture of bland smooth muscle fascicules admixed with numerous osteoclast-like giant cells (hematoxylinphloxin-safran; magnification: 10 ).
FIG. 3. The osteoclast-like giant cells show strong cytoplasmic positivity with CD68, whereas the spindle cell component does not express CD68 (magnification: 20 ).
smooth muscle actin, desmin, and caldesmon. The OLGCs were strongly positive for CD68 (Fig. 3). All tumoral cells were negative for CD10, CD117, WT1, p53, and cytokeratin AE1/AE3. There was weak and focal staining for estrogen receptor. On follow-up, 12 mo after surgery, the patient is well, without evidence of recurrent or metastatic disease.
tumors: endometrial carcinosarcoma (1), endometrial adenosquamous carcinoma (2), endometrial stromal sarcoma (3), extraosseous malignant giant cell tumor (4), and malignant fibrous histiocytoma (5). Nine cases of uterine leiomyosarcoma harboring OLGC have been reported (6–14), but this unusual feature has never been, to our knowledge, described in association with a uterine leiomyoma. The origin and significance of OLGC in tumors are still debated; they show striking morphologic similarity with osteoclasts, harboring ample eosinophilic cytoplasm and multiple bland nuclei. However, immunohistochemical and ultrastructure studies seem to point to a histiocytic origin (10,14). Their presence in numerous tumors has been thought to originate from a stromal reaction secondary to cytokine elaboration by tumor cells. Their clinical significance nonetheless remains unknown. As OLGC have predominantly been reported in the uterus in association with leiomyosarcomas, extensive sampling and a thorough search for atypia in a smooth muscle tumor is recommended in their presence. In 1 case report, malignant features compatible with leiomyosarcoma were found in 5 of 95 sections of an otherwise classic leiomyoma (10). OLGC were only identified in association with the malignant component of the tumor. This tumor showed an aggressive clinical course, with the patient dying of metastatic disease 5 mo postoperatively. In our case, numerous levels were ordered on the blocks where OLGC were identified, and did not reveal any atypical features suggestive of leiomyosarcoma. Endometrial stromal sarcoma with OLGC has also
DISCUSSION OLGC have been reported in association with numerous epithelial and mesenchymal tumors in various anatomic locations. In the uterus, they have only been described in association with malignant
FIG. 2. Osteoclast-like giant cells showing bland nuclear features (hematoxylin-phloxin-safran; magnification 20 ).
Int J Gynecol Pathol Vol. 35, No. 1, January 2016
Copyright r 2015 International Society of Gynecological Pathologists.
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M. -C. GUILBERT ET AL.
been reported (3). Interestingly, in this case, the OLGC was predominantly confined to areas showing smooth muscle differentiation. Multinucleated giant cells have been described in bizarre leiomyoma (also called symplastic or pleomorphic) (15). However, these giant cells show varying degree of pleomorphism and nuclei atypia. These leiomyomas are clinically benign, and the main challenge for the pathologist is differentiating them from leiomyosarcomas. In contrast, OLGC show bland nuclear features and are monotonous throughout the tumor. Finally, OLGC have been reported in uterine giant cell tumors, closely resembling giant cell tumors of bone (4). Giant cells in this entity are morphologically and immunohistochemically identical to the ones identified in our case. The main difference lies in the cells surrounding the OLGC: in giant cell tumors, these are oval to round mononuclear cells, that also express CD68. We did not identify a mononuclear cell population in our tumor, neither morphologically or immunohistochemically. In summary, we describe a case of a uterine leiomyoma with OLGC, which, to our knowledge, has never been reported before. This finding expands the morphologic diversity of uterine leiomyomas. As OLGC are most commonly associated with leiomysarcoma, their presence in a uterine smooth muscle tumor should prompt a thorough search for atypical features.
REFERENCES 1. Amant F, Vandenput I, Van Gorp T, et al. Endometrial carcinosarcoma with osteoclast-like giant cells. Eur J Gynaecol Oncol. 2006;27:92–4.
2. Imura J, Tomita S, Ono Y, et al. Endometrial adenosquamous carcinoma with osteoclast-like giant cells: immunohistochemistry and histogenesis. APMIS. 2005;113:140–4. 3. Fadare O, McCalip B, Mariappan MR, et al. An endometrial stromal tumor with osteoclast-like giant cells. Ann Diagn Pathol. 2005;9:160–5. 4. Manglik N, Sawicki J, Saad A, et al. Giant cell tumor of uterus resembling osseous giant cell tumor: case report and review of literature. Int J Surg Pathol. 2012;20:618–22. 5. Fujii S, Kanzaki H, Konishi I, et al. Malignant fibrous histiocytoma of the uterus. Gynecol Oncol. 1987;26: 319–30. 6. van Meurs HS, Dieles JJ, Stel HV. A uterine leiomyoma in which a leiomyosarcoma with osteoclast-like giant cells and a metastasis of a ductal breast carcinoma are present. Ann Diagn Pathol. 2012;16:67–70. 7. Darby AJ, Papadaki L, Beilby JO. An unusual leiomyosarcoma of the uterus containing osteoclast-like giant cells. Cancer. 1975;36:495–504. 8. Pilon VA, Parikh N, Maccera J. Malignant osteoclast-like giant cell tumor associated with a uterine leiomyosarcoma. Gynecol Oncol. 1986;23:381–6. 9. Watanabe K, Hiraki H, Ohishi M, et al. Uterine leiomyosarcoma with osteoclast-like giant cells: histopathological and cytological observations. Pathol Int. 1996;46:656–60. 10. Aru A, Norup P, Bjerregaard B, et al. Osteoclast-like giant cells in leiomyomatous tumors of the uterus. A case report and review of the literature. Acta Obstet Gynecol Scand. 2001; 80:371–4. 11. Marshall RJ, Braye SG, Jones DB. Leiomyosarcoma of the uterus with giant cells resembling osteoclasts. Int J Gynecol Pathol. 1986;5:260–8. 12. Patai K, Illyes G, Varbiro S, et al. Uterine leiomyosarcoma with osteoclast like giant cells and long standing systemic symptoms. Gynecol Oncol. 2006;102:403–5. 13. Sukpan K, Khunamornpong S, Suprasert P, et al. Leiomyosarcoma with osteoclast-like giant cells of the uterus: a case report and literature review. J Med Assoc Thai. 2010;93: 510–5. 14. Li Y, Xu XL, Wang J. Leiomyosarcoma with prominent osteoclast-like giant cells: a clinicopathologic analysis of 7 cases and review of literature. Chin J Pathol [Zhonghua bing li xue za zhi]. 2011;40:363–7. 15. Downes KA, Hart WR. Bizarre leiomyomas of the uterus: a comprehensive pathologic study of 24 cases with long-term follow-up. Am J Surg Pathol. 1997;21:1261–70.
Int J Gynecol Pathol Vol. 35, No. 1, January 2016
Copyright r 2015 International Society of Gynecological Pathologists.
Case Report
Uterine Leiomyoma With Osteoclast-like Giant Cells Marie-Christine Guilbert,
M.D.,
Vanessa Samoue¨lian,
M.D., Ph.D.,
and Kurosh Rahimi,
M.D.
Summary: Numerous histologic variants of uterine leiomyomas have been described. The main interest in recognizing these variants is differentiating them from leiomyosarcoma. Osteoclast-like giant cells (OLGC) have been described in association with leiomyosarcoma but to our knowledge, never with leiomyoma. We here report the case of a 58-year-old woman who underwent an elective total hysterectomy with bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy for endometrial atypical complex hyperplasia. Multiple typical uterine leiomyoma were identified. One of them showed numerous OLGC admixed with fascicules of bland smooth muscle cells. No atypical features were identified in multiple sections of this otherwise classic uterine leiomyoma. The OLGC showed strong positivity for CD68. The patient, on follow-up, did not show any evidence of recurrent or metastatic disease. This unusual finding expands the morphologic spectrum of uterine leiomyomas. When confronted with a uterine smooth muscle cell tumor with an OLGC component, it is important to search for atypical features diagnostic of leiomyosarcoma. Key Words: Uterine leiomyoma— Osteoclast-like giant cells—Uterine leiomyosarcoma.
foci suspicious for endometrioid adenocarcinoma Grade 1. The preoperative magnetic resonance imaging showed a thickened endometrium and multiple uterine leiomyomas. The patient underwent an elective total hysterectomy with bilateral salpingooophorectomy and bilateral pelvic lymphadenectomy by robotic surgery. A hysterectomy specimen weighting 183 was received in pathology. There were multiple intramural white, fasciculated nodules, measuring between 0.8 and 6 cm in diameter. No necrosis or hemorrhagic areas were identified. The cervix, fallopian tubes, and ovaries were unremarkable. Histologic examination of the specimen revealed complex hyperplasia with atypia and multiple uterine leiomyomas, characterized by a bland uniform spindle cell proliferation arranged in interlacing fascicules. One of the leiomyomas, measuring 3.5 cm, showed in addition numerous benign-appearing OLGCs that were intimately admixed with the smooth muscle bundles (Figs. 1, 2). There were no mitosis, no necrosis, and no significant cellular atypia. Immunohistochemically, the spindled cells showed strong positivity for
Leiomyomas are the most common tumor of the uterus. They can take on a variety of morphologic aspects, making their differentiation from their malignant counterpart, leiomyosarcoma, sometimes challenging. Osteoclast-like giant cells (OLGC) are rarely seen in the uterus. They have predominantly been described in association with leiomyosarcoma. Here we report a case of a uterine leiomyoma with a significant OLGC component.
CASE REPORT A 58-yr-old woman presented with an 8 month history of postmenopausal bleeding. Endometrial biopsy showed complex hyperplasia with atypia, with From the Department of Pathology (M.-C.G., K.R.); and Division of Gyneco-Oncology (V.S.), Centre hospitalier de l’Universite´ de Montre´al (CHUM), Montre´al, QC, Canada. The authors declare no conflict of interest. Address correspondence and reprint requests to Marie-Christine Guilbert, MD, Department of Pathology, Centre hospitalier universitaire de Montre´al, 1560 rue Sherbrooke Est, Montre´al, QC, Canada H2L 4M1. E-mail: [email protected].
DOI: 10.1097/PGP.0000000000000204
30
Copyright r 2015 International Society of Gynecological Pathologists.
UTERINE LEIOMYOMA WITH OLGCS
31
FIG. 1. Lobular architecture of bland smooth muscle fascicules admixed with numerous osteoclast-like giant cells (hematoxylinphloxin-safran; magnification: 10 ).
FIG. 3. The osteoclast-like giant cells show strong cytoplasmic positivity with CD68, whereas the spindle cell component does not express CD68 (magnification: 20 ).
smooth muscle actin, desmin, and caldesmon. The OLGCs were strongly positive for CD68 (Fig. 3). All tumoral cells were negative for CD10, CD117, WT1, p53, and cytokeratin AE1/AE3. There was weak and focal staining for estrogen receptor. On follow-up, 12 mo after surgery, the patient is well, without evidence of recurrent or metastatic disease.
tumors: endometrial carcinosarcoma (1), endometrial adenosquamous carcinoma (2), endometrial stromal sarcoma (3), extraosseous malignant giant cell tumor (4), and malignant fibrous histiocytoma (5). Nine cases of uterine leiomyosarcoma harboring OLGC have been reported (6–14), but this unusual feature has never been, to our knowledge, described in association with a uterine leiomyoma. The origin and significance of OLGC in tumors are still debated; they show striking morphologic similarity with osteoclasts, harboring ample eosinophilic cytoplasm and multiple bland nuclei. However, immunohistochemical and ultrastructure studies seem to point to a histiocytic origin (10,14). Their presence in numerous tumors has been thought to originate from a stromal reaction secondary to cytokine elaboration by tumor cells. Their clinical significance nonetheless remains unknown. As OLGC have predominantly been reported in the uterus in association with leiomyosarcomas, extensive sampling and a thorough search for atypia in a smooth muscle tumor is recommended in their presence. In 1 case report, malignant features compatible with leiomyosarcoma were found in 5 of 95 sections of an otherwise classic leiomyoma (10). OLGC were only identified in association with the malignant component of the tumor. This tumor showed an aggressive clinical course, with the patient dying of metastatic disease 5 mo postoperatively. In our case, numerous levels were ordered on the blocks where OLGC were identified, and did not reveal any atypical features suggestive of leiomyosarcoma. Endometrial stromal sarcoma with OLGC has also
DISCUSSION OLGC have been reported in association with numerous epithelial and mesenchymal tumors in various anatomic locations. In the uterus, they have only been described in association with malignant
FIG. 2. Osteoclast-like giant cells showing bland nuclear features (hematoxylin-phloxin-safran; magnification 20 ).
Int J Gynecol Pathol Vol. 35, No. 1, January 2016
Copyright r 2015 International Society of Gynecological Pathologists.
32
M. -C. GUILBERT ET AL.
been reported (3). Interestingly, in this case, the OLGC was predominantly confined to areas showing smooth muscle differentiation. Multinucleated giant cells have been described in bizarre leiomyoma (also called symplastic or pleomorphic) (15). However, these giant cells show varying degree of pleomorphism and nuclei atypia. These leiomyomas are clinically benign, and the main challenge for the pathologist is differentiating them from leiomyosarcomas. In contrast, OLGC show bland nuclear features and are monotonous throughout the tumor. Finally, OLGC have been reported in uterine giant cell tumors, closely resembling giant cell tumors of bone (4). Giant cells in this entity are morphologically and immunohistochemically identical to the ones identified in our case. The main difference lies in the cells surrounding the OLGC: in giant cell tumors, these are oval to round mononuclear cells, that also express CD68. We did not identify a mononuclear cell population in our tumor, neither morphologically or immunohistochemically. In summary, we describe a case of a uterine leiomyoma with OLGC, which, to our knowledge, has never been reported before. This finding expands the morphologic diversity of uterine leiomyomas. As OLGC are most commonly associated with leiomysarcoma, their presence in a uterine smooth muscle tumor should prompt a thorough search for atypical features.
REFERENCES 1. Amant F, Vandenput I, Van Gorp T, et al. Endometrial carcinosarcoma with osteoclast-like giant cells. Eur J Gynaecol Oncol. 2006;27:92–4.
2. Imura J, Tomita S, Ono Y, et al. Endometrial adenosquamous carcinoma with osteoclast-like giant cells: immunohistochemistry and histogenesis. APMIS. 2005;113:140–4. 3. Fadare O, McCalip B, Mariappan MR, et al. An endometrial stromal tumor with osteoclast-like giant cells. Ann Diagn Pathol. 2005;9:160–5. 4. Manglik N, Sawicki J, Saad A, et al. Giant cell tumor of uterus resembling osseous giant cell tumor: case report and review of literature. Int J Surg Pathol. 2012;20:618–22. 5. Fujii S, Kanzaki H, Konishi I, et al. Malignant fibrous histiocytoma of the uterus. Gynecol Oncol. 1987;26: 319–30. 6. van Meurs HS, Dieles JJ, Stel HV. A uterine leiomyoma in which a leiomyosarcoma with osteoclast-like giant cells and a metastasis of a ductal breast carcinoma are present. Ann Diagn Pathol. 2012;16:67–70. 7. Darby AJ, Papadaki L, Beilby JO. An unusual leiomyosarcoma of the uterus containing osteoclast-like giant cells. Cancer. 1975;36:495–504. 8. Pilon VA, Parikh N, Maccera J. Malignant osteoclast-like giant cell tumor associated with a uterine leiomyosarcoma. Gynecol Oncol. 1986;23:381–6. 9. Watanabe K, Hiraki H, Ohishi M, et al. Uterine leiomyosarcoma with osteoclast-like giant cells: histopathological and cytological observations. Pathol Int. 1996;46:656–60. 10. Aru A, Norup P, Bjerregaard B, et al. Osteoclast-like giant cells in leiomyomatous tumors of the uterus. A case report and review of the literature. Acta Obstet Gynecol Scand. 2001; 80:371–4. 11. Marshall RJ, Braye SG, Jones DB. Leiomyosarcoma of the uterus with giant cells resembling osteoclasts. Int J Gynecol Pathol. 1986;5:260–8. 12. Patai K, Illyes G, Varbiro S, et al. Uterine leiomyosarcoma with osteoclast like giant cells and long standing systemic symptoms. Gynecol Oncol. 2006;102:403–5. 13. Sukpan K, Khunamornpong S, Suprasert P, et al. Leiomyosarcoma with osteoclast-like giant cells of the uterus: a case report and literature review. J Med Assoc Thai. 2010;93: 510–5. 14. Li Y, Xu XL, Wang J. Leiomyosarcoma with prominent osteoclast-like giant cells: a clinicopathologic analysis of 7 cases and review of literature. Chin J Pathol [Zhonghua bing li xue za zhi]. 2011;40:363–7. 15. Downes KA, Hart WR. Bizarre leiomyomas of the uterus: a comprehensive pathologic study of 24 cases with long-term follow-up. Am J Surg Pathol. 1997;21:1261–70.
Int J Gynecol Pathol Vol. 35, No. 1, January 2016
Copyright r 2015 International Society of Gynecological Pathologists.
