Abstract
Keywords
Primary Objective
Competency 2: Organ System Pathology; Topic FU: Female reproductive: uterus, cervix, and vagina; Learning Goal 1: Uterine Neoplasia.
Secondary Objective
Competency 1: Disease Mechanisms and Processes; Topic N: Neoplasia; Learning Goal 3: Characteristics of Neoplasia.
Patient Presentation
A 42-year-old African American woman presents to her gynecologist with concerns about increased heaviness of her menses and a feeling of pelvic fullness. Menses occur every 28 days and last for 7 days. She has no intercycle bleeding. She is otherwise healthy. Her routine pap smears have been normal. She does not report a family history of ovarian, uterine, or cervical cancer.
Diagnostic Findings, Part 1
Bimanual pelvic examination shows a 16-week sized, irregular, anteverted, mobile uterus. The remaining physical examination is unremarkable.
Question/Discussion Points, Part 1
What Is the Differential Diagnosis of an Irregular, Enlarged Uterus?
Differential Diagnosis of an Irregular Enlarged Uterus.
Diagnostic Findings, Part 2
The patient’s ultrasound is shown in Figure 1. Transvaginal ultrasound showing a single echogenic, well-defined intramural mass (arrow).
Question /Discussion Points, Part 2
How Would You Describe the Findings of the Ultrasound (Figure 1)?
Transvaginal ultrasound demonstrates a single echogenic, well-defined intramural mass measuring approximately 5 cm.
On other ultrasound views, not shown on this manuscript, more hypoechoic and submucosal masses were noted, and bilateral adnexa demonstrated no abnormalities.
What Is Your Working Diagnosis?
Leiomyoma, also known as a fibroid, is the most likely diagnosis, based on the patient’s race and age, presenting complaints of heavy bleeding and pelvic fullness, examination revealing an enlarged but irregular uterus, and ultrasound findings.
What Is the Clinical Presentation of Leiomyomas?
The presentation is varied and patient-dependent, guided by the size, location, and amount of masses. If detected on physical examination, they are described as solid, mobile masses with irregular contours. 2 The most common complaints are of dysmenorrhea, or painful bleeding, and menorrhagia, or heavy bleeding. Pelvic fullness or compression of the bladder or rectum, leading to constipation or urinary urgency or retention, can occur in patients with subserosal or large intramural leiomyomas. Infertility has also been noted as a complaint, especially in those with submucosal leiomyomas. It is important to note that some women remain asymptomatic. 4,5
On gross inspection, leiomyomas are rubbery, well-circumscribed, widely variable in size, and are usually white with a whorled appearance (Figure 2). Color of the mass may change depending on its composition, such as in yellow or tan if adipocytes are present, or due to changes in its blood supply, such as red in a pregnant patient. 3 Leiomyomas are characterized by their location: subserosal, intramural, submucosal.
Gross image of a leiomyomata. Well-circumscribed, white whorled nodule.
What Is the Natural History of Leiomyomas?
Uterine leiomyomas arise from the myometrium. They are found in reproductive-aged women, as they respond to the action of estradiol and progesterone. Mature smooth muscle cells, under estrogen and progesterone influence, exert a paracrine effect on immature cells resulting in their proliferation and creation of the smooth muscle mass. 6
Each leiomyoma has been noted to grow at its own rate. They have also been shown to undergo periods of spontaneous growth and/or regression, straying away from the idea that they grow in a linear manner during a woman’s reproductive life. In pregnant women, leiomyomas were noted to maintain this nonlinear growth, with the biggest size increase noted within the first trimester. With decrease of sex steroid hormones, they regress after menopause. 7
What Is the Histologic Appearance of a Leiomyoma?
Histology demonstrates a well-circumscribed lesion composed of elongated spindle cells with eosinophilic cytoplasm and cigar-shaped central nuclei arranged in intersecting fascicles (Figure 3). Mitotic figures are rare. Occasionally infarct-type necrosis, as opposed to coagulative-type tumor cell necrosis, is seen. 3 Presence of tumor cell necrosis should trigger a search for increased mitotic figures and leiomyosarcoma should be considered (Figure 4). It should be noted, there are uterine smooth muscle tumors that fall into a category between benign leiomyoma and malignant leiomyosarcoma. The tumors, called smooth muscle tumor of uncertain malignant potential, look clinically and grossly like leiomyoma; however, they contain increased mitotic activity and mild nuclear atypia that falls short of a designation of malignant.
Microscopic image of leiomyoma. Smooth muscle cells in fascicular bundles with bland nuclei and absence of mitotic figures or necrosis. Hematoxylin and eosin stained section at ×100 magnification.
Leiomyosarcoma. Cells with cigar-shaped nuclei and at least moderate nuclear atypia are seen with numerous mitotic figures evident (circles). Tumor cells necrosis was seen in other areas of the tumor (not pictured). Immunostains for smooth-muscle actin (SMA) and desmin were positive in the pictured cells, supporting the smooth muscle origin. Hematoxylin and eosin stained section at ×400 magnification.
What Treatments Can We Offer Patients With Leiomyomata Uteri?
There are many options for the management of fibroids, both medical and surgical (see Tables 2 and 3). Medical options, such as nonsteroidal anti-inflammatories, oral contraception, tranexamic acid, and levonorgestrel intrauterine devices, can be used to decrease the bleeding. Other medical treatments such as gonadotropin releasing hormones agonists and selective estrogen receptor modulators may decrease the size of the leiomyomas in preparation for surgical management. Surgical options include removal of the leiomyoma or removal of the whole uterus as well as decreasing the blood supply to the leiomyomas via uterine artery embolization.
Medical Treatment Options for Leiomyoma.
Surgical Treatment Options for Leiomyoma.
It is important to tailor the treatment to the patient’s needs, including permanent resolution of symptoms and fertility wishes. 4,5
What Is a Leiomyosarcoma?
A leiomyosarcoma is a malignant smooth muscle tumor. Grossly, they appear as large, fleshy masses that are irregularly shaped with visible hemorrhage or necrosis. 3 Histologic evaluation shows cells with cigar-shaped nuclei, nuclear atypia, and numerous mitotic figures (Figure 4). Necrosis and hemorrhage can often be observed. Immunostains for SMA and desmin can be used to support the smooth muscle origin of a leiomyosarcoma.
What Is the Risk for Malignant Transformation of a Leiomyoma?
Leiomyosarcoma is an uncommon diagnosis thought to occur sporadically; that is to say, leiomyosarcoma does not arise from a preexisting leiomyoma. However, there are reported cases contradicting this argument. Alterations in chromosome 1, such as loss of the short arm or mutations resulting in abnormal proteins, have been identified in these rare instances. Overall, the incidence of leiomyosarcoma has been noted to increase in those who are on tamoxifen treatment for breast cancer. 3,8,9
Teaching Points
Leiomyomas are smooth muscle neoplasms which are commonly found in the uterus of reproductive age women. Masses grow at their own rate and regress after menopause.
Uterine leiomyomas can be in the following locations: submucosal, subserosal, or intramural.
The clinical presentation of leiomyomas varies per patient and includes an occult presentation, heavy bleeding, pelvic pain/fullness, and bowel and/or bladder symptoms.
The diagnosis is made via a thorough history and physical examination, with assistance of ultrasound imaging. Pathologic evaluation of the mass gives a definitive diagnosis.
Grossly, leiomyomas appear as white, well-circumscribed masses. On histology, spindle cells arranged in intersecting fascicles are appreciated.
Treatment approach is patient dependent. Multiple options can be used and include medical or surgical treatment.
Leiomyosarcomas are malignant smooth muscle masses that mostly arise de novo.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The article processing fee for this article was funded by an Open Access Award given by the Society of ‘67, which supports the mission of the Association of Pathology Chairs to produce the next generation of outstanding investigators and educational scholars in the field of pathology. This award helps to promote the publication of high-quality original scholarship in
