This 41-year-old para 0, gravida 0 woman presented with a history of vaginal bleeding. She has no
history of cervical disease or malignancy. On exam she is an obese Caucasian female in no evident
distress. Pelvic examination shows an enlarged friable cervix. A SurePath cervical sample was taken as
well as a biopsy. (Images MRH-B 1, MRH-B 2, MRH-B 3)
Case 7 - Figure 1 - SurePath™ Papanicolaou stain, high power: This image shows the spindle shaped malignant cells in a SurePath cervical preparation. The cells are quite variable in shape and size. The nuclei have an open chromatin pattern with a prominent nucleolus.
Case 7 - Figure 2 - SurePath™ Papanicolaou stain, high power: A tumor diathesis is seen here. On SurePath preparations necrotic material is generally seen as clumps of amorphous material mixed with blood and neutrophils.
Case 7 - Figure 3 - SurePath™ Papanicolaou stain, high power: A mitotic figure is seen here and the image again demonstrates the marked pleomorphism of the malignant cells.
The SurePath preparation is very cellular and consists almost entirely of an abnormal population of
cells with pleomorphic nuclei with cleared out chromatin and a prominent single nucleolus. The cells
vary in size and range from rounded to spindle in shape. There is a moderate amount of soft, cyanophilic
cytoplasm. The cells are predominantly single but occasional clusters are seen. Focally, necrotic
material is noted. Rare benign squamous and endocervical glandular cells are seen. No evidence of HPV
cytopathic effect or other squamous abnormality is seen.
Extra slides prepared from the liquid sample are stained for Cytokeratin, Vimentin, Actin and CD-10.
Keratin stains the benign squamous cells and Actin is negative. Vimentin is positive in the malignant
cells and CD-10 is focally positive. The biopsy taken at the same time also shows a poorly
differentiated neoplasm with a similar staining pattern, which was diagnosed, as consistent with high
grade stromal sarcoma.
History and Clinical Follow-up
The patient subsequently underwent radical hysterectomy, bilateral salpingo-oophorectomy, lymph node
dissection and omentectomy, which showed a high grade endometrial stromal sarcoma involving the uterus,
cervix right ovary and pelvic and para-aortic lymph nodes. Following the surgery she underwent an
extensive course of chemotherapy. She is currently free of disease after 3 years.
Diagnosis: High Grade Endometrial Sarcoma
Endometrial sarcomas are unusual lesions most often occurring as a component of high grade endometrial
carcinoma (malignant mullerian mixed tumors (MMMT) or adenosarcomas) or occasionally as a pure sarcoma.
Endometrial stromal sarcoma is a protean tumor with numerous phenotypes and vary from low grade lesions
with a low recurrence rate to poorly differentiated sarcomas with little if any differentiation and a
very poor prognosis. The division of endometrial stroma sarcomas into low-grade and high grade has
somewhat fallen out of favor and some now favor limiting the designation of endometrial stromal sarcoma
to those lesions formerly referred to as "low-grade". High grade lesions often show no evidence of
definitive endometrial stromal origin and are often show considerable histologic resemblance to MMMTs.
Although most cases of stromal sarcoma can be diagnosed on morphologic grounds, immunohistochemical
stains may be useful. In low grade lesions, the stromal cells are typically positive for Vimentin,
smooth muscle Actin and CD-10 and often reactive to keratin and Desmin. The reactivity to CD-10 is
interesting and useful as almost all of the smooth tumors of the uterus are negative for this antibody.
However, not unexpectedly, positivity to CD-10 falls off sharply in the high grade lesions. In one study
only 2 of 5 high grade endometrial stromal sarcomas were positive.  In another study 4 of 6
high grade sarcomas were positive but the staining was usually focal. 
The cytology of uterine sarcomas, and in particular the findings on routine cervical samples, is not
well characterized. One recent study has looked at this issue and found that the conventional Pap smear
was relatively insensitive (60%) in detecting endometrial sarcomas.3 Of the smears with abnormal cells
present, the vast majority appeared to be epithelial in origin. It was felt that these cells for the
most part were derived from the carcinomatous component of a MMMT. In 2 cases atypical spindle cells
were identified but none of the smears had diagnostic sarcomatous elements. Antidotally, my own
experience has mimicked this and while I have searched smears from known MMMT patients I have only rarely
found cells that appear to be stromal in nature.
With the advent of liquid cervical cytology, it is now possible to prepare additional samples for
immunoperoxidase staining with various antibodies. While for the most part this will not be necessary it
may be of use in lesions such as the one shown here. This particular specimen was quite cellular and was
composed almost entirely of poorly differentiated cells. The differential diagnosis was quite broad (see
below) and immunostaining could quickly point in the proper direction. In this case stains for
Cytokeratin and Smooth Muscle Actin were negative and positive for Vimentin with focal positivity for
CD-10 indicating an endometrial stromal origin. In other cases, staining may be useful to distinguish
metastasis from primary lesions.
The cytologic findings in this case are those of a poorly differentiated neoplasm either primary or
metastatic to the cervix. The features of malignancy are quite evident with numerous highly atypical,
poorly cohesive cells with prominent nucleoli. A tumor diathesis is seen in the background. The
differential diagnosis would encompass primary epithelial cervical lesions such as poorly differentiated
squamous cell carcinoma (possibly with metaplastic sarcomatoid features) or adenocarcinoma. Also to be
considered would be endometrial lesions with extension to the cervix. Rare lesions such as primary
cervical melanoma are possible and finally, metastatic lesions must be considered. The following
summarizes the pertinent features of each of these.
Poorly Differentiated Nonkeratinizing Squamous Carcinoma
| Most often well enough differentiated to be of obvious epithelial origin with rounded to polygonal cells.|
| May be associated with high grade intraepithelial lesional material.|
| Tend to be more cohesive with a mixture of groups and single cells.|
| Nuclei are hyperchromatic often with dense, coarse, irregularly dispersed chromatin and variably shaped and sized nucleoli.|
| Occasional keratinized abnormal cells may be present.|
| Should stain for keratin and be negative for stromal markers.|
| May be accompanied by a squamous intraepithelial lesion or squamous component.|
| Similar features to poorly differentiated squamous cell carcinoma with paler, more granular cytoplasm.|
| Nuclear chromatin is less coarse than squamous lesions but still hyperchromatic with prominent nucleoli.|
| Often impossible to distinguish poorly differentiated cervical adenocarcinoma from high grade endometrial carcinoma.|
| History is often the most helpful factor.|
| Look for unusual cellular arrangements such as:|
| || Indian filing or paranuclear vacuoles in metastatic breast carcinoma.|
| || Isolated three dimensional glandular arrangements with no necrosis in exfoliated ovarian or fallopian tube carcinoma|
| || Pallisading columnar groups with goblet cells and marked necrosis in colonic adenocarcinoma.|
- Zhu XQ, Shi YF, Cheng XD, Zhao CL, Wu YZ. Immunohistochemical markers in differential diagnosis of endometrial stromal sarcoma and cellular leiomyoma. Gynecol Oncol. 2004 Jan;92(1):71-9
- McCluggage WG, Sumathi VP, Maxwell P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology. 2001 Sep;39(3):273-8.
- Snyder MJ, Robboy SJ, Vollmer RT, Dodd LG. An abnormal cervicovaginal cytology smear in uterine carcinosarcoma is an adverse prognostic sign: analysis of 25 cases. Am J Clin Pathol. 2004 Sep;122(3):434-9.
- Oliva E, Clement PB, Young RH. Endometrial stromal tumors: an update on a group of tumors with a protean phenotype. Adv Anat Pathol. 2000 Sep;7(5):257-81.
- Brooks SE, Zhan M, Cote T, Baquet CR. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999. Gynecol Oncol. 2004 Apr;93(1):204-8.
- Wang X, Khoo US, Xue WC, Cheung AN. Cervical and peritoneal fluid cytology of uterine sarcomas. Acta Cytol. 2002 May-Jun;46(3):465-9.