Leiomyomas

Uterine leiomyomas (commonly called fibroids) are perhaps the most common tumor in women. They are benign smooth muscle neoplasms that may occur singly, but most often are multiple. Most leiomyomas have normal karyotypes, but approximately 40% have a simple chromosomal abnormality. Several cytogenetic subgroups have been recognized: a balanced translocation between chromosomes 12 and 14 (i.e., t(12;14)(q14-q15;q23-q24)), partial deletions of the long arm of chromosome 7 (i.e., del(7)(q22-q32)), trisomy 12, and rearrangements of 6p, 3q, and 10q. The rearrangements of 12q14 and 6p involving the HMGIC and HMGIY genes, respectively, which are also implicated in a variety of other benign neoplasms. Both genes encode closely related DNA-binding factors that regulate chromatin structure .

Morphology. Leiomyomas are sharply circumscribed, discrete, round, firm, gray-white tumors varying in size from small, barely visible nodules to massive tumors that fill the pelvis. Except in rare instances, they are found within the myometrium of the corpus. Only infrequently do they involve the uterine ligaments, lower uterine segment, or cervix. They can occur within the myometrium (intramural), just beneath the endometrium (submucosal) (Fig. 22-32A; see also Fig. 22-23D), or beneath the serosa (subserosal).

Whatever their size, the characteristic whorled pattern of smooth muscle bundles on cut section usually makes these lesions readily identifiable on gross inspection. Large tumors may develop areas of yellow-brown to red softening (red degeneration).

On histologic examination, the leiomyoma is composed of whorled bundles of smooth muscle cells that resemble the uninvolved myometrium (Fig. 22-32B). Usually, the individual muscle cells are uniform in size and shape and have the characteristic oval nucleus and long, slender bipolar cytoplasmic processes. Mitotic figures are scarce. Benign variants of leiomyoma include atypical or bizarre (symplastic) tumors with nuclear atypia and giant cells, and cellular leiomyomas. Importantly, both have a low mitotic index. An extremely rare variant, benign metastasizing leiomyoma, consists of a uterine tumor that extends into vessels and migrates to other sites, most commonly the lung. Another variant, disseminated peritoneal leiomyomatosis, presents as multiple small nodules on the peritoneum. Both are considered benign despite their unusual behavior.

Leiomyomas of the uterus, even when they are extensive, may be asymptomatic. The most important symptoms are abnormal bleeding, compression of the bladder (urinary frequency), sudden pain if disruption of blood supply occurs, and impaired fertility. Myomas in pregnant women increase the frequency of spontaneous abortion, fetal malpresentation, uterine inertia, and postpartum hemorrhage. Malignant transformation (leiomyosarcoma) within a leiomyoma is extremely rare.

Leiomyosarcomas

These uncommon malignant neoplasms arise de novo from the myometrium or endometrial stromal precursor cells. In contrast to leiomyomas, leiomyosarcomas have complex, highly variable karyotypes that frequently include deletions.68

Morphology. Leiomyosarcomas grow within the uterus in two somewhat distinctive patterns: bulky, fleshy masses that invade the uterine wall, or polypoid masses that project into the uterine lumen (Fig. 22-33A). On histologic examination, they contain a wide range of atypia, from those that are extremely well differentiated to highly anaplastic, pleomorphic lesions (Fig. 22-33B). The distinction from leiomyomas is based on nuclear atypia, mitotic index, and zonal necrosis. With few exceptions, the presence of 10 or more mitoses per 10 high-power (400×) fields indicates malignancy, particularly if accompanied by cytologic atypia and/or necrosis. If the tumor contains nuclear atypia or large (epithelioid) cells, 5 mitoses per 10 high-power (400×) fields are sufficient to justify a diagnosis of malignancy. Rare exceptions include mitotically active leiomyomas in young or pregnant women, and caution should be exercised in interpreting such neoplasms as malignant. A proportion of smooth muscle neoplasms may be impossible to classify and are called smooth muscle tumors of "uncertain malignant potential".

Leiomyosarcomas are equally common before and after menopause, and have a peak incidence at 40 to 60 years of age. These tumors have a striking tendency to recur after removal, and more than half eventually metastasize through the bloodstream to distant organs, such as lungs, bone, and brain. Dissemination throughout the abdominal cavity is also encountered. The 5-year survival rate averages about 40%. The well-differentiated lesions have a better prognosis than the anaplastic lesions, which have a 5-year survival rate of only 10% to 15%.