Case 3 -
Kristen A. Atkins
University of Virginia Health Science Center
Click on each slide thumbnail image for an enlarged view
A 25 year old healthy Caucasian woman has an intramucosal
uterine myoma resulting in two miscarriages. An endometrial curettage is performed followed by a
myomectomy. Slide is from the myomectomy (a Ki67 is provided for easier assessment of proliferation
Common problems with smooth muscle tumors of the uterus
- Burns B, Curry RH, Bell ME. 1979 >5mits/10 hpf
- Perrone T, Dehner LP. "prognostically favorable mitotically active smooth
muscle tumors". Becoming clear that one feature such as mitoses was not going to be uniformly predictive
of a bad outcome.
- Evans HL, Chawla SP, Simpson C, Finn KP. 46 cases1988 tumor size,
mitoses, tumor necrosis important. Mitoses, atypia, necrosis, vascular invasion not important when size
taken into consideration.
- Bell et al 213 cases, regression analysis, good clinical follow up. Three
dependent variables (atypia, CTCN, mitoses)
Enter STUMP: Tumors with five to ten mitoses per ten high-power fields and with mild or moderate
cellular atypia OR Tumors with two to four mitoses per ten high-power fields and severe cellular atypia
- Layfield et al (IHC approach) confirms histologic approach
- Introduction of STUMP
- 1994 definition
- Current definitions have additional features (single cell necrosis, myxoid
areas, epithelioid areas, etc). It is a histologically heterogeneous group of smooth muscle tumors.
- Review of the literature and STUMP definitions
The problem with the literature is that STUMP, an inherently heterogeneous group, is lumped together.
Literature often harmful. One radiologic study talks about the imaging features of STUMP as if this is a
distinct entity. What we need to know is how subcategories behave. For instance what is the outcome in
those patients with all features of usual leiomyoma but single cell necrosis. What is outcome in
patients with moderate atypia but mitoses <10/10 and no CTCN.
- Behavior of SMT
- Time to recurrence 2 yrs
- Treatment no reliable chemo. Role of hormonal rx.
- Leiomyomas, cellular, mitotically active, "symplastic"
- Clinical Pathologic quandary of STUMP
- How to treat/follow
- Post childbearing vs childbearing as in this case
- IHC helpful?
- Recent studies: gene expression array, IHC papers
- Molecular studies
- Believe sarcomas/ leiomyoma are separate entities
- Importance of the STUMP category
A. Want to use conservatively but not eliminate- always have borderline cases
- Clinical course, this case
- This endometrial biopsy was initially called cellular leiomyoma on the endometrial
biopsy. Given the patient's age and presentation the diagnosis is understandable. The myomectomy was
classified as STUMP for the following reasons: moderate cytologic atypia and focal single cell
necrosis. 6 months later she presented with a perirectal and abdominal mass, which demonstrated a smooth
muscle tumor with identical histologic features. 3 months later she developed adenopathy showing a lymph
node involved by the same smooth muscle tumor. The aggressiveness of this tumor was no longer uncertain
and so it was diagnosed as leiomyosarcoma. The patient was treated with progesterone, which markedly
slowed down the tumor growth. She was taken off progesterone to have a pregnancy. After the delivery of
a healthy baby, she developed additional adenopathy and a small bowel metastasis. She is currently being
maintained on progesterone without progression of disease.
- Leiomyosarcomas are rare but critical to identify given the high mortality. It is not
surprising that most STUMPS behave like leiomyomas given the rarity of leiomyosarcomas. However, it is
important to remember that when we diagnose a lesion as STUMP we are actually NOT giving a diagnosis. We
are officially saying "I don't know what this is" but in a more palatable way. This case illustrates
three points: 1. not all leiomyosarcomas will be histologically obvious and the STUMP category is
important- we just need to use it conservatively. 2. Once a STUMP metastasizes, it is no longer STUMP.
It is now leiomyosarcoma. 3. From a biological standpoint it has clearly shown its malignant potential
yet it is progressing slowly and is responsive to hormonal treatment, more like a low grade sarcoma (as
suggested by the histology).
- Bell SW, Kempson RL, Hendrickson MR.Problematic uterine smooth muscle neoplasms. A clinicopathologic study of 213 cases. Am J Surg Pathol. 1994 Jun;18(6):535-58.
- Blom R, Guerrieri C, Stal O, Malmstrom H, Simonsen E. Leiomyosarcoma of the uterus: A clinicopathologic, DNA flow cytometric, p53, and mdm-2 analysis of 49 cases. Gynecol Oncol. 1998 Jan;68(1):54-61.
- Burns B, Curry RH, Bell ME. Morphologic features of prognostic significance in uterine smooth muscle tumors: a review of eighty-four cases. Am J Obstet Gynecol. 1979 Sep 1;135(1):109-14.
- Evans HL, Chawla SP, Simpson C, Finn KP. Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors. Cancer. 1988 Nov 15;62(10):2239-47.
- Gokaslan H, Turkeri L, Kavak ZN, et al Differential diagnosis of smooth muscle tumors utilizing p53, pTEN and Ki-67 expression with estrogen and progesterone receptors. Gynecol Obstet Invest. 2005;59(1):36-40. Epub 2004 Sep 20.
- Kelley TW, Borden EC, Goldblum JR. Estrogen and progesterone receptor expression in uterine and extrauterine leiomyosarcomas: an immunohistochemical study. Appl Immunohistochem Mol Morphol. 2004 Dec;12(4):338-41.
- Layfield LJ, Liu K, Dodge R, Barsky SH. Uterine smooth muscle tumors: utility of classification by proliferation, ploidy, and prognostic markers versus traditional histopathology. Arch Pathol Lab Med. 2000 Feb;124(2):221-7.
- Perrone T, Dehner LP. Prognostically favorable "mitotically active" smooth-muscle tumors of the uterus. A clinicopathologic study of ten cases. Am J Surg Pathol. 1988 Jan;12(1):1-8.
- Quade BJ, Wang TY, Sornberger K, Dal Cin P, Mutter GL, Morton CC. Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling. Genes Chromosomes Cancer. 2004 Jun;40(2):97-108.
- Solomon LA, Schimp VL, Ali-Fehmi R, Diamond MP, Munkarah AR. Clinical update of smooth muscle tumors of the uterus. J Minim Invasive Gynecol. 2005 Sep-Oct;12(5):401-8.