I love questions from our readers. If one person has the question, undoubtedly many others do as well. Recently, someone asked: “Is there a fixed number of mitotic figures that implies a diagnosis of leiomyosarcoma instead of leiomyoma?” Everyone who has been in a pathology gross room (where we cut specimens open) for more than 10 minutes has seen a leiomyoma or two. Leiomyomas are benign smooth-muscle tumors that occur in the uterine wall. They are very, very common, and are often found incidentally in a uterus removed for unrelated reasons.

It’s important, obviously, to be able to differentiate between leiomyoma and its malignant counterpart, leiomyosarcoma. Fortunately, leiomyosarcomas are not as common as leiomyomas. In fact, they’re pretty rare. Which is good, because they are fairly nasty malignancies, with a tendency to metastasize early (often to the lung) and recur after surgery. The overall 5 year survival rate is 40%; cases that are poorly differentiated have a dismal 5 year survival rate of 10-15%.

One thing to settle right away is the misguided idea that leiomyosarcomas arise from leiomyomas. They don’t! Or at least, they virtually never do. The incidence of malignant transformation of leiomyomas is vanishingly rare. Leiomyosarcomas arise de novo from myometrial cells or endometrial stromal precursor cells.

Gross appearance
Leiomyosarcomas are usually either bulky, invasive masses within the uterine wall, or polypoid masses projecting into the uterine lumen. Leiomyomas are also either within the uterine wall or bulging into the lumen – but they are not invasive (they look like well-circumscribed, rubbery masses). Leiomyomas generally have a whorled, firm cut surface, and they are usually not necrotic or hemorrhagic (unless they are large, in which case they may have areas of reddish brown softening. Leiomyosarcomas, on the other hand, are often necrotic and hemorrhagic, and they don’t have a whorled, firm, creamy white cut surface like leiomyomas do.

Microscopic appearance
Of course, to really be sure whether you’re dealing with a leiomyoma or a leiomyosarcoma, you have to look under the microscope. Leiomyomas are composed of bundles of smooth muscle cells that look very much like those of the normal myometrium. The cells have an oval nucleus and are long and slender, and usually there is very little atypia (although there are some benign variants of leiomyoma that have atypia). Atypia or not, they have a very low mitotic index.

Leiomyosarcomas may be well-differentiated or poorly-differentiated. The well-differentiated ones look a lot like leiomyomas, and the poorly differentiated ones have a lot of atypia and pleomorphism. Either way, you should see an increased mitotic rate in order to call it leiomyosarcoma. If the tumor is pretty well-differentiated, then you need to see 10 mitoses per 10 high power (400x) fields. If atypia is present, or if you see large epithelioid cells, then you only need 5 mitoses per 10 hpf. Necrosis, if present, pushes you towards leiomyosarcoma too.

Sometimes, you just can’t tell which it is: leiomyoma or leiomyosarcoma. In that case, you call it “smooth muscle tumor of uncertain malignant potential.”