Endometrial stromal sarcoma

A tumour resembling endometrial stroma.

Clinical

Pulmonary metastases occur on average ten years after the diagnosis of the primary tumour⁸.

Histology

The classical appearance is of small cells with scant cytoplasm and round to oval nuclei. The accompanying vasculature resembles spiral arterioles, as well as staghorn vessels and anastomosing capillaries.

variants

• With fibromyxoid features, with a stroma varying from myxoid to hyalinised and bland spindle cells resembling fibroblasts or myofibroblasts⁷. The vasculature commonly resembles that of classical ESS and there may be a paucicellular zone between capillaries and the condensed stroma.

• With smooth muscle differentiation, consisting of fascicles of spindle cells with elongated nuclei and eosinophilic cytoplasm⁷. These are so-called "stromomyomas".

Patients may have a primary with classical histology and metastases with variant (sometimes with other, classical, metastases) histology⁷.

Immunohistochemistry

SMA	1/121, 3/33, 2/24, 0/75, 8/13 (3 diffuse, 5 focal: all 13 cases were pulmonary metastases)8, 0/1 (metastasis to lung)10
desmin	1/121, 12/242, 3/33, 2/24, 0/75, 7/13 (3 diffuse, 4 focal: all 13 cases were pulmonary metastases)8, 1/6 (2 stromal nodules and 8 stromal sarcomas)9, 0/1 (metastasis to lung)10
h-caldesmon	0/121, 0/212, 0/6 (2 stromal nodules and 8 stromal sarcomas)9
HHF-35	3/33, 2/24
MyoD1	0/1 (metastasis to lung)10
vimentin	3/33, 2/24, 7/75, 13/14 (diffuse: all 13 cases were pulmonary metastases)8, 1/1 (metastasis to lung)10
cytokeratin	0/75
AE1 / AE3	6/13 (3 diffuse, 3 focal: all 13 cases were pulmonary metastases)8, 2/10 (2 stromal nodules and 8 stromal sarcomas. three additional cases showed scattered positive cells)9
MNF116	0/1 (metastasis to lung)10
Cam 5.2	1/13 (focal: all 13 cases were pulmonary metastases)8, 2/10 (2 stromal nodules and 8 stromal sarcomas. three additional cases showed scattered positive cells)9, 0/1 (metastasis to lung)10
BerEP4	0/1 (metastasis to lung)10
CD10	17/196, 9/10 (2 stromal nodules and 8 stromal sarcomas)9
Calponin	7/10 (2 stromal nodules and 8 stromal sarcomas. staining was stronger in areas of smooth muscle differentiation.)9, 1/1 (metastasis to lung)10
oestrogen receptors	2/24, 2/75, 13/13 (diffuse: all 13 cases were pulmonary metastases)8
progesterone receptors	3/33, 2/24, 14/14 (diffuse: all 13 cases were pulmonary metastases)8
calretinin	1/7
inhibin	1/13 (focal: all 13 cases were pulmonary metastases)8, 0/10 (2 stromal nodules and 8 stromal sarcomas)9
Chromogranin	1/13 (focal: all 13 cases were pulmonary metastases)8, 0/1 (metastasis to lung)10
Synaptophysin	0/1 (metastasis to lung)10
PGP9.5	1/1 (metastasis to lung)10
NSE	0/1 (metastasis to lung)10
S-100	0/1 (metastasis to lung)10
HMB45	1/13 (focal: all 13 cases were pulmonary metastases)8
CD34	1/13 (focal: all 13 cases were pulmonary metastases)8, 0/10 (2 stromal nodules and 8 stromal sarcomas)9, 0/1 (metastasis to lung)10
CD56	1/1 (metastasis to lung)10
CD68	0/1 (metastasis to lung)10
CD99	0/10 (2 stromal nodules and 8 stromal sarcomas)9
CD117	0/10 (2 stromal nodules and 8 stromal sarcomas)9
MIC2	0/1 (metastasis to lung)10

Those cases with variant histology show a higher rate of positivity for muscle markers. There may be a CD10+ endometrial stromal component and a CD10- smooth muscle / myofibroblastic component⁷.

desmin	7/10 (with strong expression in 4/4 cases containing smooth muscle or myofibroblasts)7, 4/4 (2 stromal nodules and 8 stromal sarcomas)9
h-caldesmon	6/7 (including 6/6 cases containing smooth muscle)7, 4/4 (2 stromal nodules and 8 stromal sarcomas)9
CD10	10/12 (expression seen in morphological smooth muscle)7

Differential diagnosis

leiomyomatous tumours: h-caldesmon appears to be the more specific muscle marker; use in combination with CD10. An initial report suggests that Histone Deacetylase 8 may be infromative. The recognition of endometrial stromal differentiation within a tumour showing muscle differentiation should lead to classification as a sarcoma⁷.

leiomyoma, including benign metastasizing leiomyoma

• intravascular leiomyomatosis

• disseminated peritoneal leiomyomatosis

• lymphangioleiomyomatosis

if located in the ovary: ovarian granulosa cell tumours: CD10 in combination with inhibin

metastatic endometrial stromal sarcoma from superficial cervicovaginal myofibroblastoma

metastases to the gynaecological tract:

• gastrointestinal stromal tumour

• low-grade extrauterine leiomyosarcoma

• low-grade fibrosarcoma

• spindle cell rhabdomyosarcoma

• peripheral nerve sheath tumour

• within the lung:

  • metastasizing leiomyoma

  • intravascular leiomyomatosis

  • metastatic low grade leiomyosarcoma

  • lymphangioleiomyomatosis

  • fibroleiomyomatous hamartoma

  • fibrosarcoma

  • carcinoid¹⁰

  • synovial sarcoma

  • haemangiopericytoma

Prognosis

The prognosis is excellent, even in the presence of pulmonary metastases⁸.

References

¹Rush, D. S., Tan, J., Baergen, R. N., Soslow, R. A. h-Caldesmon, a novel smooth muscle-specific antibody, distinguishes between cellular leiomyoma and endometrial stromal sarcoma. Am J Surg Pathol 2001;25:253-258.

²Nucci, M. R., O'Connell, J. T., Huettner, P. C., Cviko, A., Sun, D., Quade, B. J. h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors. Am J Clin Pathol 2001;25:455-463.

³Fukunaga, M., Ishihara, A., Ushigome, S. Extrauterine low-grade endometrial stromal sarcoma: report of three cases. Pathology International 1998;48:297-302

⁴Fukunaga, M., Miyazawa, Y., Ushigome, S. Endometrial low-grade stromal sarcoma with ovarian sex cord-like differentiation: report of two cases with an immunohistochemical and flow cytometric study. Pathology International 1997;47:412-415

⁵Tosi, P., V. Sforza, et al. (1989). "Estrogen receptor content, immunohistochemically determined by monoclonal antibodies, in endometrial stromal sarcoma." Obstet Gynecol 73(1): 75-8.

⁶McCluggage, W. G., Sumathi, V. P., Maxwell, P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology 2001;39:273-278.

⁷Yilmaz, A., D. S. Rush, et al. (2002). "Endometrial stromal sarcomas with unusual histologic features: a report of 24 primary and metastatic tumors emphasizing fibroblastic and smooth muscle differentiation." Am J Surg Pathol 26(9): 1142-50.

⁸Aubry, M. C., J. L. Myers, et al. (2002). "Endometrial stromal sarcoma metastatic to the lung: a detailed analysis of 16 patients." Am J Surg Pathol 26(4): 440-9.

⁹Oliva, E., R. H. Young, et al. (2002). "An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies." Am J Surg Pathol 26(4): 403-12.

¹⁰Khan, O. A., K. Rogers, et al. (2004). "Lung metastases as an initial presentation of endometrial stromal sarcoma: the utility of the CD10 antibody." Histopathology 45(5): 544-6.

This page last revised 25.12.2003.

©SMUHT/PW Bishop