3.1.10: Leiomyosarcoma

3.1.10.1 Definition

It is a primary malignant mesenchymal tumor of smooth muscle cells in both visceral organs and non-visceral structures. The most common primary sites of leiomyosarcomas include the uterus, retroperitoneum, gastrointestinal tract, and extremities. Uterine leiomyosarcoma is one of the rarest female genital tumors.²¹

3.1.10.2 Pathogenesis

They arise from the myometrium or the connective tissue elements of the endometrium. They have complex chromosomal abnormalities, including chromosomal deletions. Several genetic mutations have been identified, including TP53, RB1, and MED 12, among several others. Occasional cases have been reported with tamoxifen use.

3.1.10.3 Morphology

Macroscopically, leiomyosarcomas are soft tumors with areas of hemorrhage and necrosis.

Microscopically, there are three subtypes: spindle-cell type and the less common myxoid and epithelioid types. Spindle-cell type contains spindle cells with marked cellular atypia/nuclear pleomorphism, >10 mitoses per 10 high-power fields, and areas of necrosis (Figure 3.1.30 A); these features differentiate leiomyosarcoma from leiomyoma (at least two of these are required to diagnose leiomyosarcoma). Myxoid tumors have abundant myxoid stroma. Epithelioid tumor cells resemble epithelial cells (epithelial-like, hence the name); these cells are round or polygonal with eosinophilic cytoplasm (Figure 3.1.30 B).

Figure 3.1.30 (A) Leiomyosarcoma: Variable atypia, often with cytoplasmic vacuoles at both ends of nuclei and frequent mitoses.
Image Source: Kobayashi, Eiji, Takuhei Yokoyama, Satoshi Nakagawa, Shinya Matsuzaki, Toshihiro Kimura, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Yumiko Hori, Eiichi Morii and Tadashi Kimura. " Histopathology of leiomyosarcoma of the uterus." (July 31, 2013). This work is distributed under a CC BY 4.0 license. Original Source: "Pedunculated Sub-Serous Leiomyosarcoma Mimicking Ovarian Cancer: Case Report and Review of Literature". Gynecology & Obstetrics 3, No. 3 (2012). This work is distributed under a CC BY 4.0 license. DOI:10.4172/2161-0932.1000157. Image available from Wikimedia Commons.

Figure 3.1.30 (B) Histopathology of epithelioid leiomyosarcoma of the uterus. 40x, H&E staining.
Image Source: King, Luke, Radhika P Gogoi, Christopher Hummel, Zongming Chen and Ashlee Smith. "Histopathology of epithelioid leiomyosarcoma of the uterus." 40x, H&E staining. (July 12, 2018). This work is distributed under a CC BY 4.0 license. Original Source: "High Grade Uterine Sarcoma with Concurrent Metastatic Adenocarcinoma to the Uterus: A Case Report". Obstetrics and Gynaecology Cases - Reviews 5, No. 4 (2018). This work is distributed under a CC BY 4.0 license. DOI:10.23937/2377-9004/1410127. Image available from Wikimedia Commons.

3.1.10.4 Clinical Presentation

They are usually diagnosed in the 6th decade of life, with an average age of 53 reported at diagnosis. These are aggressive tumors with a worse prognosis than endometrial endometrioid carcinoma. Typically presenting as a large pelvic mass (greater than 5 cm in diameter), its signs and symptoms include vaginal bleeding, pelvic pain, a sense of fullness in the pelvis or abdomen, dyspareunia, and dysuria, although some patients are asymptomatic. Survival outcomes are impacted by age at diagnosis, tumor size, and disease stage. An increase in each of these prognostic categories is associated with poorer prognosis. Diagnosis mainly depends on histopathological assessment since imaging techniques are not diagnostic.

Glossary terms

Atypia

abnormality in cells in tissue

Cytoplasm

internal material between the cell membrane and nucleus of a cell, mainly consisting of a water-based fluid called cytosol, within which are all the other organelles and cellular solute and suspended materials

Dyspareunia

genital pain before, during, or after intercourse

Dysuria

painful urination

Eopsinophils

granulocytes that stain with eosin; they release antihistamines and are especially active against parasitic worms

Epithelium

sheets of cells that cover the exterior surfaces of the body, line internal cavities and passageways, and form certain glands; also known as epithelial tissue

Hemorrhage

excessive bleeding [

Mesenchymal

refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue

Myometrium

smooth muscle layer of uterus that allows for uterine contractions during labor and expulsion of menstrual blood

Necrosis

accidental death of cells and tissues

Pleomorphism

able to assume different forms

Stroma

tissue that forms the structure of an organ or body part

Visceral

pertaining to internal organs

Footnotes

21. Kim, Suyeon, Hyunsik Bae, and Hyun Soo Kim. “Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review.” Diagnostics 14, no. 2 (2024): 160. This work is distributed under a CC BY license. doi.org/10.3390/diagnostics14020160; Dall, Genevieve V., Anne Hamilton, Gayanie Ratnayake, Clare Scott, and Holly Barker. “Interrogating the Genomic Landscape of Uterine Leiomyosarcoma: A Potential for Patient Benefit.” Cancers 14, no. 6 (2022): 1561. This work is distributed under a CC BY license. doi.org/10.3390/cancers14061561

Image Acknowledgements

King, Luke, Radhika P Gogoi, Christopher Hummel, Zongming Chen and Ashlee Smith. "Histopathology of epithelioid leiomyosarcoma of the uterus." 40x, H&E staining. (July 12, 2018). This work is distributed under a CC BY 4.0 license. Original Source: "High Grade Uterine Sarcoma with Concurrent Metastatic Adenocarcinoma to the Uterus: A Case Report". Obstetrics and Gynaecology Cases - Reviews 5, No. 4 (2018). This work is distributed under a CC BY 4.0 license. DOI:10.23937/2377-9004/1410127. Image available from Wikimedia Commons.