- Email: [email protected]
Angiosarcoma of the Uterus: Report of 2 New Cases With Deviant Clinicopathologic Features and Review of the Literature
Available online at www.sciencedirect.com
Annals of Diagnostic Pathology 12 (2008) 217 – 221
Angiosarcoma of the Uterus: Report of 2 New Cases With Deviant Clinicopathologic Features and Review of the Literature Loredana Cardinale, MD a , Maurizio Mirra, MD a , Carlo Galli, MD a , John R. Goldblum, MD b , Stefano Pizzolitto, MD c , Giovanni Falconieri, MD c,⁎ a
Departments of Pathology, General Hospital, Lodi, Italy b Cleveland Clinic, Cleveland, Ohio, USA c General Hospital S. Maria della Misericordia, Udine, Italy
Abstract
Keywords:
A few cases of uterine angiosarcoma have been detailed in the literature: 2 new cases are herein described featuring some unusual clinical or phenotypic differences compared with previously published cases, such as occurrence in premenopausal age or a poorly differentiated histology. The patients were 35 and 81 years old, and both presented with extrauterine spread and evidence of distant metastases. Grossly, they were fleshy, hemorrhagic, and necrotic. Microscopically, they were made up of poorly differentiated, epithelioid, or spindle cells. In one case, the neoplastic growth deceitfully recalled a poorly differentiated leiomyosarcoma showing focal rudimentary endothelial differentiation. The other index case was characterized by a more pronounced vascular pattern, the neoplasm was composed of spindle cells arranged in loose channels. A diffuse immunopositivity for CD31, CD34, and factor VIII–related antigen was detected. Tumor cells were negative for other tested antigens including keratins, desmin, actins, and H-caldesmon. One patient died shortly during the follow-up, whereas the other is alive with evidence of disseminated disease. Occurrence in childbearing age or a deviant histologic pattern, as documented in this report, may be added to the clinicopathologic spectrum of uterine angiosarcoma. © 2008 Elsevier Inc. All rights reserved. Angiosarcoma; Uterine tumors; Immunohistochemistry
1. Introduction Uterine mesenchymal tumors other than leiomyosarcomas and endometrial stromal sarcomas are uncommon. In particular, angiosarcomas are very rare, and only 10 cases have been described in the English literature for the past 20 years [1-8], 4 of which were retrieved from the consultation files of the Armed Forces Institute of Pathology [6]. In this article, we describe 2 new cases of angiosarcoma occurring in the uterus and provide a brief review of the literature.
⁎ Corresponding author. Department of Pathology, General Hospital and University Hospital, S. Maria della Misericordia, I 33100 Udine, Italy. Tel.: +39 0432 552826; fax: +39 0432 552830. E-mail address: [email protected] (G. Falconieri). 1092-9134/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2007.08.001
2. Case reports 2.1. Case 1 An 81-year-old white woman sought medical advice because of lower abdominal pain and anemia (hemoglobin, 7.7 g/dL; hematocrit, 24.4%). Physical examination revealed an enlarged, fixed, and tender uterus: a biopsy of the endometrium was positive for a malignant, spindle cell neoplasm. Total hysterectomy with bilateral salpingooophorectomy was carried out. An exploratory laparotomy revealed several firm nodules scattered within the peritoneal surface. No further therapy was administered. The patient died 6 months after the operation with evidence of diffuse, intra-abdominal neoplastic spread. The uterus weighed 200 g and measured 8 × 7 × 4.5 cm. The cut surface was vaguely nodular and fasciculated. The endometrial cavity was filled with hemorrhagic material. The cervix and adnexa were
218
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
Fig. 1. Wide neoplastic infiltration of the inner endometrium and myometrium by irregular tumor cell fascicles. Residual of lamina basalis may be recognized (case 1, ×100).
Fig. 3. Tumor cells often show abortive vascular differentiation with cytoplasmic vacuolation containing red blood cells (case 1, ×400).
unremarkable. Histologic examination of the uterine specimen showed a malignant tumor made up of haphazardly arranged cell fascicles diffusely infiltrating the whole thickness of the myometrium (Fig. 1). Tumor cells were mitotically active, either epithelioid or spindle, and sometimes displayed optically clear spaces within the cytoplasm (Figs. 2 and 3). Scattered areas of coagulative necrosis were recognized as well. There was microscopic evidence of neoplastic infiltration of the cervix, fallopian tubes, and ovaries. An omental biopsy specimen was positive for malignancy. A cytologic examination of peritoneal lavage fluid was positive for malignant cells.
shortness of breath, dry cough, and gastrointestinal reflux. Past medical history was unremarkable. The patient's obstetric history included 2 pregnancies as well as cesarean deliveries. A computed tomography scan performed at the time of hospitalization revealed a large pleural effusion, diffuse omental thickening, and a left-sided abdominal mass. Total hysterectomy with bilateral salpingo-oophorectomy was performed. The uterus weighed greater than 2400 g and contained a dumbbell-shaped, well-circumscribed subserosal tan-gray mass measuring 25 cm in larger dimension. The tumor had the appearance of a hemorrhagic and necrotic leiomyoma. Additional neoplastic nodules were identified in the omentum. Fluid cytology smears obtained from pelvic washing and pleural effusion specimens were positive for malignant cells. Microscopically, the uterine tumor featured haphazardly arranged spindle cells. The tumoral growth had a striking noncohesive quality with distinct optical clear spaces. Cell lining had a vague endothelial appearance and featured bullet-like, hyperchromic nuclei (Figs. 4 and 5). A moderately collagenized ground substance was also noticed.
2.2. Case 2 A 35-year-old white woman was brought to the emergency department because of a 1-week history of
2.3. Immunohistochemical studies A panel of antibodies was applied to paraffin sections of the tumors following the directions published elsewhere [9]. Tumor cells were positive for CD31 (Fig. 6A), Fli-1, and factor VIII–related antigen. The remaining immunostain results were negative. Keratins and muscle markers, including actins, desmin, and H-caldesmon, were reactive with remnants of endometrial lamina basalis and myometrium, respectively (Fig. 6B). 3. Discussion Fig. 2. Individual tumor cell fascicles features poorly differentiated epithelioid or spindle cells with stainable cytoplasm and vesicular nuclei. Residual myometrial tissue imparts a vague nested or alveolar architecture (case 1, ×200).
Most angiosarcomas are tumors of the scalp or somatic soft tissues. In visceral locations, angiosarcomas are observed sporadically in several organs including the lung,
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
219
Fig. 4. Diffusely infiltrating tumor showing irregularly anastomosing empty spaces within the preexisting myometrium (case 2, ×200).
pleura, breast, and liver. Uterine angiosarcomas appear to be very rare, and only 10 cases investigated by means of immunohistochemistry or electron microscopy have been reported in the medical literature for the past 20 years (Table 1). Additional 8 cases retrieved by Prempree et al [10] had been mentioned in the medical literature between 1902 and 1979 before the introduction of routine immunohistochemical investigations. Most patients were postmenopausal (age range, 4976 years; mean age, 65 years), and the clinical history was usually rapid with a poor and rapid outcome. If bona fide cases reported prior the introduction of special techniques are considered, then angiosarcoma of the uterus have been reported in 4 premenopausal patients aged 17, 28, 31, and 34 years, and a relatively long survival was described for some of them (see the detailed review by Ongkasuwan et al [4]). Prognostic factors cannot be assessed given the paucity of observation; however, in one of the recent cases reported
Fig. 5. Higher magnification details malignant spindle cells lining the pseudovascular spaces and exhibiting nuclear hyperchromasia (case 2, ×400).
Fig. 6. The neoplastic cells are positive for CD31 (A) and negative for desmin (B).
by Schammel and Tavassoli [6], the patient was alive more than 3 years after the diagnosis of angiosarcoma, apparently the only case of uterine angiosarcoma exhibiting a polypoid/ exophytic rather than a diffuse neoplastic infiltration of the myometrium. It is therefore possible, as claimed by the authors, that the endocavitary growth pattern might be viewed as a favorable prognostic indicator. The microscopic recognition of angiosarcoma arising in the uterus may pose diagnostic problems especially when the classic “freely anastomosing vascular channels” customarily described in better differentiated lesions are lacking or when the tumor, like the one detailed here, is composed of epithelioid, spindle cells with minimal features of endothelial derivation. In these cases, the tumor can be rubricated under a different heading and the possibility of a leiomyosarcoma entertained because of the fascicular arrangement and the spindly quality of cells. However, leiomyosarcoma usually presents with nodular masses rather than a wide infiltration of myometrium. Microscopically, tumor fascicles tend to retain an intersecting pattern at 90°, like their benign
220
Table 1 Summary of reported cases of uterine angiosarcoma between 1987 and 1994 Year
No. of cases
Age (y)
Presenting symptoms
Macroscopic features
Microscopic features
Special studies
Therapy
Follow-up/Survival
Witkin et al
1987
1
71
Vaginal bleeding
Massive enlargement of uterus by a fleshy tumor
IP (FVIII-RA+) and EM
RT
Tumor recurrence 2 mo after surgery
Milne et al
1989
1
76
Uterine bleeding, anemia, hydronephrosis
Massive enlargement of uterus by necrotic tumor
IP (FVIII-RA+)
NA
6 mo
Quinonez et al
1991
1
65
Hemorrhagic uterine discharge
EM
CT
Alive 4 y after surgery
Tallini et al
1993
1
56
Vaginal bleeding
4.7-cm hemorrhagic mass within bulky uterus Multiple hemorrhagic leiomyomas
4 mo
1993
1
61
1993
4, see note
49
See note
See note
None. widespread angiosarcoma documented at autopsy None
1 mo
Schammel and Tavassoli
3 mo
58
Hemorrhagic uterine discharge after RT for carcinoma of cervix 7 y before Pelvic mass, vaginal bleeding Vaginal bleeding, anemia
IP (FVIII-RA+, UAE+, keratins+) and EM IP (FVIII-RA+) and EM
CT
Morrel et al
Angiosarcoma with anastomosing vascular channels; associated with leiomyomas Pleomorphic epithelioid cells forming vascular spaces Pleomorphic and spindle cells forming vascular spaces Angiosarcoma associated with leiomyomas Angiosarcoma with vascular channels
CT, RT
2 mo
70
Vaginal bleeding
None
Alive N3 y after surgery
75 58
Vaginal bleeding Vaginal bleeding
None CT, RT
7 mo 2 mo
Drachenberg et al
1994
1
10-cm uterine mass resected for uterine massive hemorrhage 6.3-kg mass of lower uterus 12-cm hemorrhagic mass 5-cm polypoid lesion of endometrium invading half myometrium 6.3 cm of lower uterus Multiple leiomyomata and a 12-cm hemorrhagic mass
Angiosarcoma within a leiomyoma
IP (FVIII-RA+, UAE+)
Note: 2 patients had concurrent leiomyoma; all cases exhibited anastomosing vascular channels, epithelioid, and spindle cell morphology; note (b): all cases positive for CD31, CD34, and FVIII-RA. IP indicates immunoperoxidase; EM, electron microscopy; FVIII-RA, factor VIII–related antigen; CT, chemotherapy; RT, radiation therapy; UAE, Ulex Europaeus.
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
Authors
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
counterpart, and the nuclei have blunt ends and are cigarshaped. A careful evaluation of fine cytologic details reveals a fibrillary quality of the leiomyosarcoma cells. Immunohistochemical staining for muscle markers, including desmin, actins, and H-caldesmon, is expected in leiomyosarcoma, whereas angiosarcomas are most often positive for endothelial cell antigens such as CD31, factor VIII–related antigen, and Fli-1. Investigation by electron microscopy also proves useful if Weibel-Palade bodies can be demonstrated [3,5,7,8]. A keratin-negative sarcomatoid carcinoma is also difficult to rule out on a morphologic basis only. However, strong immunoreaction for endothelial markers and negativity for epithelial membrane antigen (EMA) along with focal, albeit unequivocal, microscopic features of abortive endothelial differentiation are helpful clues. The cause of angiosarcoma in this uncommon location remains largely speculative. However, 4 patients had concurrent uterine leiomyomas or leiomyomatosis, and in at least 2 cases, there was an intimate association between the 2 lesions [1,7], suggesting that the increased vascular proliferation secondary to a mechanical, pressure effect of adjacent leiomyomata might have induced the endothelial neoplastic transformation [1]. On the other hand, the role of alternative factors claimed for some visceral angiosarcomas, including radio- or chemotherapy (in the case of breast or liver) or foreign bodies (bone and soft tissue), appears questionable. Interestingly, a case of angiosarcoma of the vagina has been reported in a patient who received radiotherapy for squamous carcinoma of the cervix [10]. In conclusion we have reported 2 additional cases of uterine angiosarcoma. Our cases differ from those published to date in that they show some deviant clinical and pathologic features: in one case, the tumor occurred in a premenopausal woman; in the other case, a sarcomatous growth recalling a conventional poorly differentiated leiomyosarcoma or a sarcomatoid carcinoma was noticed. In that setting, essential immunohistochemistry for endothe-
221
lial markers proved to be a confirmatory diagnostic tool. Further cases of uterine angiosarcoma may therefore potentially be singled out among cases rubricated as poorly differentiated spindle cell sarcomas of the myometrium, where endothelial differentiation is focal especially if immunohistochemistry for specific endothelial markers was not done or was not available. Acknowledgment The Authors are indebted to Dr Christopher D. Ackley, Methodist Hospital, San Antonio, TX, for providing information on case 2. References [1] Drachenberg CB, Faust FJ, Borkowski A, et al. Epithelioid angiosarcoma of the uterus arising in a leiomyoma with associated ovarian and tubal angiomatosis. Am J Clin Pathol 1994;102:388-9. [2] Milne DS, Hinshaw K, Malcolm AJ, et al. Primary angiosarcoma of the uterus: a case report. Histopathology 1990;16:203-5. [3] Morrel B, Mulder AF, Chadha S, et al. Angiosarcoma of the uterus following radiotherapy for squamous cell carcinoma of the cervix. Eur J Obstet Gynecol Reprod Biol 1993;49:193-7. [4] Ongkasuwan C, Taylor JE, Tang CK, et al. Angiosarcomas of the uterus and ovary: clinicopathologic report. Cancer 1982;49:1469-75. [5] Quinonez GE, Paraskevas MP, Diocee MS, et al. Angiosarcoma of the uterus: a case report. Am J Obstet Gynecol 1991;164:90-2. [6] Schammel DP, Tavassoli FA. Uterine angiosarcomas: a morphologic and immunohistochemical study of four cases. Am J Surg Pathol 1998;22:246-50. [7] Tallini G, Price FV, Carcangiu ML. Epithelioid angiosarcoma arising in uterine leiomyomas. Am J Clin Pathol 1993;100:514-8. [8] Witkin GB, Askin FB, Geratz JD, et al. Angiosarcoma of the uterus: a light microscopic, immunohistochemical, and ultrastructural study. Int J Gynecol Pathol 1987;6:176-84. [9] Nadji M, Nassiri M, Morales AR. Efficient tumor immunohistochemistry: a differential diagnosis-driven approach. Chicago: American Society of Clinical Pathologists Press; 2006. [10] Prempree T, Tang CK, Hatef A, et al. Angiosarcoma of the vagina: a clinicopathologic report. A reappraisal of the radiation treatment of angiosarcomas of the female genital tract. Cancer 1983;51:618-22.
Annals of Diagnostic Pathology 12 (2008) 217 – 221
Angiosarcoma of the Uterus: Report of 2 New Cases With Deviant Clinicopathologic Features and Review of the Literature Loredana Cardinale, MD a , Maurizio Mirra, MD a , Carlo Galli, MD a , John R. Goldblum, MD b , Stefano Pizzolitto, MD c , Giovanni Falconieri, MD c,⁎ a
Departments of Pathology, General Hospital, Lodi, Italy b Cleveland Clinic, Cleveland, Ohio, USA c General Hospital S. Maria della Misericordia, Udine, Italy
Abstract
Keywords:
A few cases of uterine angiosarcoma have been detailed in the literature: 2 new cases are herein described featuring some unusual clinical or phenotypic differences compared with previously published cases, such as occurrence in premenopausal age or a poorly differentiated histology. The patients were 35 and 81 years old, and both presented with extrauterine spread and evidence of distant metastases. Grossly, they were fleshy, hemorrhagic, and necrotic. Microscopically, they were made up of poorly differentiated, epithelioid, or spindle cells. In one case, the neoplastic growth deceitfully recalled a poorly differentiated leiomyosarcoma showing focal rudimentary endothelial differentiation. The other index case was characterized by a more pronounced vascular pattern, the neoplasm was composed of spindle cells arranged in loose channels. A diffuse immunopositivity for CD31, CD34, and factor VIII–related antigen was detected. Tumor cells were negative for other tested antigens including keratins, desmin, actins, and H-caldesmon. One patient died shortly during the follow-up, whereas the other is alive with evidence of disseminated disease. Occurrence in childbearing age or a deviant histologic pattern, as documented in this report, may be added to the clinicopathologic spectrum of uterine angiosarcoma. © 2008 Elsevier Inc. All rights reserved. Angiosarcoma; Uterine tumors; Immunohistochemistry
1. Introduction Uterine mesenchymal tumors other than leiomyosarcomas and endometrial stromal sarcomas are uncommon. In particular, angiosarcomas are very rare, and only 10 cases have been described in the English literature for the past 20 years [1-8], 4 of which were retrieved from the consultation files of the Armed Forces Institute of Pathology [6]. In this article, we describe 2 new cases of angiosarcoma occurring in the uterus and provide a brief review of the literature.
⁎ Corresponding author. Department of Pathology, General Hospital and University Hospital, S. Maria della Misericordia, I 33100 Udine, Italy. Tel.: +39 0432 552826; fax: +39 0432 552830. E-mail address: [email protected] (G. Falconieri). 1092-9134/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2007.08.001
2. Case reports 2.1. Case 1 An 81-year-old white woman sought medical advice because of lower abdominal pain and anemia (hemoglobin, 7.7 g/dL; hematocrit, 24.4%). Physical examination revealed an enlarged, fixed, and tender uterus: a biopsy of the endometrium was positive for a malignant, spindle cell neoplasm. Total hysterectomy with bilateral salpingooophorectomy was carried out. An exploratory laparotomy revealed several firm nodules scattered within the peritoneal surface. No further therapy was administered. The patient died 6 months after the operation with evidence of diffuse, intra-abdominal neoplastic spread. The uterus weighed 200 g and measured 8 × 7 × 4.5 cm. The cut surface was vaguely nodular and fasciculated. The endometrial cavity was filled with hemorrhagic material. The cervix and adnexa were
218
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
Fig. 1. Wide neoplastic infiltration of the inner endometrium and myometrium by irregular tumor cell fascicles. Residual of lamina basalis may be recognized (case 1, ×100).
Fig. 3. Tumor cells often show abortive vascular differentiation with cytoplasmic vacuolation containing red blood cells (case 1, ×400).
unremarkable. Histologic examination of the uterine specimen showed a malignant tumor made up of haphazardly arranged cell fascicles diffusely infiltrating the whole thickness of the myometrium (Fig. 1). Tumor cells were mitotically active, either epithelioid or spindle, and sometimes displayed optically clear spaces within the cytoplasm (Figs. 2 and 3). Scattered areas of coagulative necrosis were recognized as well. There was microscopic evidence of neoplastic infiltration of the cervix, fallopian tubes, and ovaries. An omental biopsy specimen was positive for malignancy. A cytologic examination of peritoneal lavage fluid was positive for malignant cells.
shortness of breath, dry cough, and gastrointestinal reflux. Past medical history was unremarkable. The patient's obstetric history included 2 pregnancies as well as cesarean deliveries. A computed tomography scan performed at the time of hospitalization revealed a large pleural effusion, diffuse omental thickening, and a left-sided abdominal mass. Total hysterectomy with bilateral salpingo-oophorectomy was performed. The uterus weighed greater than 2400 g and contained a dumbbell-shaped, well-circumscribed subserosal tan-gray mass measuring 25 cm in larger dimension. The tumor had the appearance of a hemorrhagic and necrotic leiomyoma. Additional neoplastic nodules were identified in the omentum. Fluid cytology smears obtained from pelvic washing and pleural effusion specimens were positive for malignant cells. Microscopically, the uterine tumor featured haphazardly arranged spindle cells. The tumoral growth had a striking noncohesive quality with distinct optical clear spaces. Cell lining had a vague endothelial appearance and featured bullet-like, hyperchromic nuclei (Figs. 4 and 5). A moderately collagenized ground substance was also noticed.
2.2. Case 2 A 35-year-old white woman was brought to the emergency department because of a 1-week history of
2.3. Immunohistochemical studies A panel of antibodies was applied to paraffin sections of the tumors following the directions published elsewhere [9]. Tumor cells were positive for CD31 (Fig. 6A), Fli-1, and factor VIII–related antigen. The remaining immunostain results were negative. Keratins and muscle markers, including actins, desmin, and H-caldesmon, were reactive with remnants of endometrial lamina basalis and myometrium, respectively (Fig. 6B). 3. Discussion Fig. 2. Individual tumor cell fascicles features poorly differentiated epithelioid or spindle cells with stainable cytoplasm and vesicular nuclei. Residual myometrial tissue imparts a vague nested or alveolar architecture (case 1, ×200).
Most angiosarcomas are tumors of the scalp or somatic soft tissues. In visceral locations, angiosarcomas are observed sporadically in several organs including the lung,
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
219
Fig. 4. Diffusely infiltrating tumor showing irregularly anastomosing empty spaces within the preexisting myometrium (case 2, ×200).
pleura, breast, and liver. Uterine angiosarcomas appear to be very rare, and only 10 cases investigated by means of immunohistochemistry or electron microscopy have been reported in the medical literature for the past 20 years (Table 1). Additional 8 cases retrieved by Prempree et al [10] had been mentioned in the medical literature between 1902 and 1979 before the introduction of routine immunohistochemical investigations. Most patients were postmenopausal (age range, 4976 years; mean age, 65 years), and the clinical history was usually rapid with a poor and rapid outcome. If bona fide cases reported prior the introduction of special techniques are considered, then angiosarcoma of the uterus have been reported in 4 premenopausal patients aged 17, 28, 31, and 34 years, and a relatively long survival was described for some of them (see the detailed review by Ongkasuwan et al [4]). Prognostic factors cannot be assessed given the paucity of observation; however, in one of the recent cases reported
Fig. 5. Higher magnification details malignant spindle cells lining the pseudovascular spaces and exhibiting nuclear hyperchromasia (case 2, ×400).
Fig. 6. The neoplastic cells are positive for CD31 (A) and negative for desmin (B).
by Schammel and Tavassoli [6], the patient was alive more than 3 years after the diagnosis of angiosarcoma, apparently the only case of uterine angiosarcoma exhibiting a polypoid/ exophytic rather than a diffuse neoplastic infiltration of the myometrium. It is therefore possible, as claimed by the authors, that the endocavitary growth pattern might be viewed as a favorable prognostic indicator. The microscopic recognition of angiosarcoma arising in the uterus may pose diagnostic problems especially when the classic “freely anastomosing vascular channels” customarily described in better differentiated lesions are lacking or when the tumor, like the one detailed here, is composed of epithelioid, spindle cells with minimal features of endothelial derivation. In these cases, the tumor can be rubricated under a different heading and the possibility of a leiomyosarcoma entertained because of the fascicular arrangement and the spindly quality of cells. However, leiomyosarcoma usually presents with nodular masses rather than a wide infiltration of myometrium. Microscopically, tumor fascicles tend to retain an intersecting pattern at 90°, like their benign
220
Table 1 Summary of reported cases of uterine angiosarcoma between 1987 and 1994 Year
No. of cases
Age (y)
Presenting symptoms
Macroscopic features
Microscopic features
Special studies
Therapy
Follow-up/Survival
Witkin et al
1987
1
71
Vaginal bleeding
Massive enlargement of uterus by a fleshy tumor
IP (FVIII-RA+) and EM
RT
Tumor recurrence 2 mo after surgery
Milne et al
1989
1
76
Uterine bleeding, anemia, hydronephrosis
Massive enlargement of uterus by necrotic tumor
IP (FVIII-RA+)
NA
6 mo
Quinonez et al
1991
1
65
Hemorrhagic uterine discharge
EM
CT
Alive 4 y after surgery
Tallini et al
1993
1
56
Vaginal bleeding
4.7-cm hemorrhagic mass within bulky uterus Multiple hemorrhagic leiomyomas
4 mo
1993
1
61
1993
4, see note
49
See note
See note
None. widespread angiosarcoma documented at autopsy None
1 mo
Schammel and Tavassoli
3 mo
58
Hemorrhagic uterine discharge after RT for carcinoma of cervix 7 y before Pelvic mass, vaginal bleeding Vaginal bleeding, anemia
IP (FVIII-RA+, UAE+, keratins+) and EM IP (FVIII-RA+) and EM
CT
Morrel et al
Angiosarcoma with anastomosing vascular channels; associated with leiomyomas Pleomorphic epithelioid cells forming vascular spaces Pleomorphic and spindle cells forming vascular spaces Angiosarcoma associated with leiomyomas Angiosarcoma with vascular channels
CT, RT
2 mo
70
Vaginal bleeding
None
Alive N3 y after surgery
75 58
Vaginal bleeding Vaginal bleeding
None CT, RT
7 mo 2 mo
Drachenberg et al
1994
1
10-cm uterine mass resected for uterine massive hemorrhage 6.3-kg mass of lower uterus 12-cm hemorrhagic mass 5-cm polypoid lesion of endometrium invading half myometrium 6.3 cm of lower uterus Multiple leiomyomata and a 12-cm hemorrhagic mass
Angiosarcoma within a leiomyoma
IP (FVIII-RA+, UAE+)
Note: 2 patients had concurrent leiomyoma; all cases exhibited anastomosing vascular channels, epithelioid, and spindle cell morphology; note (b): all cases positive for CD31, CD34, and FVIII-RA. IP indicates immunoperoxidase; EM, electron microscopy; FVIII-RA, factor VIII–related antigen; CT, chemotherapy; RT, radiation therapy; UAE, Ulex Europaeus.
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
Authors
L. Cardinale et al. / Annals of Diagnostic Pathology 12 (2008) 217–221
counterpart, and the nuclei have blunt ends and are cigarshaped. A careful evaluation of fine cytologic details reveals a fibrillary quality of the leiomyosarcoma cells. Immunohistochemical staining for muscle markers, including desmin, actins, and H-caldesmon, is expected in leiomyosarcoma, whereas angiosarcomas are most often positive for endothelial cell antigens such as CD31, factor VIII–related antigen, and Fli-1. Investigation by electron microscopy also proves useful if Weibel-Palade bodies can be demonstrated [3,5,7,8]. A keratin-negative sarcomatoid carcinoma is also difficult to rule out on a morphologic basis only. However, strong immunoreaction for endothelial markers and negativity for epithelial membrane antigen (EMA) along with focal, albeit unequivocal, microscopic features of abortive endothelial differentiation are helpful clues. The cause of angiosarcoma in this uncommon location remains largely speculative. However, 4 patients had concurrent uterine leiomyomas or leiomyomatosis, and in at least 2 cases, there was an intimate association between the 2 lesions [1,7], suggesting that the increased vascular proliferation secondary to a mechanical, pressure effect of adjacent leiomyomata might have induced the endothelial neoplastic transformation [1]. On the other hand, the role of alternative factors claimed for some visceral angiosarcomas, including radio- or chemotherapy (in the case of breast or liver) or foreign bodies (bone and soft tissue), appears questionable. Interestingly, a case of angiosarcoma of the vagina has been reported in a patient who received radiotherapy for squamous carcinoma of the cervix [10]. In conclusion we have reported 2 additional cases of uterine angiosarcoma. Our cases differ from those published to date in that they show some deviant clinical and pathologic features: in one case, the tumor occurred in a premenopausal woman; in the other case, a sarcomatous growth recalling a conventional poorly differentiated leiomyosarcoma or a sarcomatoid carcinoma was noticed. In that setting, essential immunohistochemistry for endothe-
221
lial markers proved to be a confirmatory diagnostic tool. Further cases of uterine angiosarcoma may therefore potentially be singled out among cases rubricated as poorly differentiated spindle cell sarcomas of the myometrium, where endothelial differentiation is focal especially if immunohistochemistry for specific endothelial markers was not done or was not available. Acknowledgment The Authors are indebted to Dr Christopher D. Ackley, Methodist Hospital, San Antonio, TX, for providing information on case 2. References [1] Drachenberg CB, Faust FJ, Borkowski A, et al. Epithelioid angiosarcoma of the uterus arising in a leiomyoma with associated ovarian and tubal angiomatosis. Am J Clin Pathol 1994;102:388-9. [2] Milne DS, Hinshaw K, Malcolm AJ, et al. Primary angiosarcoma of the uterus: a case report. Histopathology 1990;16:203-5. [3] Morrel B, Mulder AF, Chadha S, et al. Angiosarcoma of the uterus following radiotherapy for squamous cell carcinoma of the cervix. Eur J Obstet Gynecol Reprod Biol 1993;49:193-7. [4] Ongkasuwan C, Taylor JE, Tang CK, et al. Angiosarcomas of the uterus and ovary: clinicopathologic report. Cancer 1982;49:1469-75. [5] Quinonez GE, Paraskevas MP, Diocee MS, et al. Angiosarcoma of the uterus: a case report. Am J Obstet Gynecol 1991;164:90-2. [6] Schammel DP, Tavassoli FA. Uterine angiosarcomas: a morphologic and immunohistochemical study of four cases. Am J Surg Pathol 1998;22:246-50. [7] Tallini G, Price FV, Carcangiu ML. Epithelioid angiosarcoma arising in uterine leiomyomas. Am J Clin Pathol 1993;100:514-8. [8] Witkin GB, Askin FB, Geratz JD, et al. Angiosarcoma of the uterus: a light microscopic, immunohistochemical, and ultrastructural study. Int J Gynecol Pathol 1987;6:176-84. [9] Nadji M, Nassiri M, Morales AR. Efficient tumor immunohistochemistry: a differential diagnosis-driven approach. Chicago: American Society of Clinical Pathologists Press; 2006. [10] Prempree T, Tang CK, Hatef A, et al. Angiosarcoma of the vagina: a clinicopathologic report. A reappraisal of the radiation treatment of angiosarcomas of the female genital tract. Cancer 1983;51:618-22.