Uterine myxoid leiomyosarcoma - a rare malignant tumor: the role of complex morphopathological assay. Review and case presentation

Abstract

Malignant mixed mesodermal sarcomas (myxoid leiomyosarcomas - MLMS) are a rare form of uterine cancer developed from the smooth muscles of the uterus. It usually affects women in the postmenopausal period and has an aggressive character with an unfavorable evolution and prognosis. This paper presents a case where MLMS was postoperatively confirmed with the aid of the histopathological (HP) examination coupled with specific immunolabeling techniques. In addition, we reviewed modern literature to compare our results. Clinically, patients may present with a pelvic tumor, vaginal bleeding, or abdominal pressure. Imagistic investigations, such as pelvic ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)-CT may support the diagnosis. Nevertheless, solely the HP examination establishes it. Macroscopically, MLMS is soft and gelatinous, unlike the conventional rigid and spiral leiomyoma appearance. Furthermore, the infiltrative, irregular tumor margin is characteristic of MLMS. From a microscopic point of view, the following are present: tumor cell necrosis, nuclear pleomorphism, and variable mitotic activity. With classical Hematoxylin-Eosin (HE) staining, myometrium presents a leiomyomatous structure and multiple nodular formations with the aspect of malignant tumor proliferation, most likely mesenchymal. We used multiple special immunolabeling techniques. Thus, we observed the intense reactivity of the cells to the anti-vimentin antibody, which immunolabeled type III intermediate filament (IF) protein expressed in mesenchymal cells, thus demonstrating tumor mesenchymal affiliation. Smooth cell positivity for alpha-smooth muscle actin (α-SMA) demonstrates that the tumor is present in its whole myometrial structure. Tumor cells also underwent mutations involving the p53 tumor suppressor gene demonstrated by the number of tumoral cells in division immunolabeled with anti-Ki67 proliferation antibody. Tumor development was demonstrated by protein activation of cyclin-dependent kinase (CDK) and the presence of c-Kit-bound hematopoietic stem cells, immunolabeled with the anti-cluster of differentiation 117 (anti-CD117) antibodies. The anti-desmin antibody demonstrates, along with α-SMA, the involvement of myocytes in the tumoral process. The following microscopic characteristics laid the foundation for the diagnosis of MLMS: irregular myometrial invasion, rare mitosis on high-power fields (HPFs), cell pleomorphism, predominant myxoid component that gave a hypocellular appearance, the matrix rich in proteoglycans and glycosaminoglycans, especially hyaluronic acid.

Figure 1

Imagistic aspects of the tumor formation, highlighted by yellow arrows: (A) Ultrasound aspect of the pelvic–abdominal tumor formation – voluminous, multilobular, heterogeneous, with solid structure, approximately 13 cm, probably of uterine affiliation; (B) Echo-Doppler examination shows poor vascularization of the tumor, especially in the periphery; (C) CT aspect of the tumor formation, voluminous, polylobulated, relatively well delimited, with heterogeneous structure and iodophilia, extensive intralesional necrosis areas and multiple iodophilic septa, with dimensions of approximately 138/134/72 mm, belonging to the uterine body, with compressive effect on the adjacent intestinal loops, without infiltrating them; (D) MRI appearance shows polylobed tumor block, heterogeneous, with tissue and cystic components, with an ancillary origin, approximately 108/140/94 mm that imprints the uterus and moves it to the right side, the tumor block includes both adnexa, present peritoneal fluid. The uterus appears compressed by the tumor mass, possibly adherent to it, measuring 77/16 mm, with several focal fibrotic remodeling at the myometrial level, including 16 mm uterine fundus fibromatous nodules. CT: Computed tomography; MRI: Magnetic resonance imaging

Figure 2

Intraoperative and postoperative macroscopic aspects of the uterine tumor, highlighted by the blue arrows: (A and B) Multilobed tumor mass, greasy, friable, easily detachable; (C) The remaining tumor after partial tumor excision, with areas of necrosis and intratumoral hemorrhages (red areas); (D) Tumor fragments detached from the tumor and sent to the extemporaneous histopathological examination, with whitish appearance, elastic consistency, lumpy, with small hemorrhagic foci; (E) Anterior aspect of the specimen, which shows on the left side the detachment area of the tumor biopsy; (F) Posterior aspect of the operatory piece, with bilateral adnexectomy – small, atrophic ovaries are observed, highlighted with green arrows

Figure 3

(A and B) Histopathological section through uterine tumor mass. Tumor proliferation with marked cell and nuclear pleomorphism, with a solid and fasciculate pattern, moderate mitotic activity, suggesting a malignant tumor, most likely mesenchymal and poorly differentiated. Hematoxylin–Eosin (HE) staining: (A) ×100; (B) ×200

Figure 4

Microscopic aspects of the tumor: (A) The density of collagen fibers in the tumor structure and asymmetrical disposition is observed, and an area of intratumoral necrosis; (B) The myxoid tumor structure is observed, highlighted by PAS–H; (C) The myxoid tumor structure is observed, highlighted by the AB staining. MT staining: (A) ×100. PAS–H staining: (B) ×100. AB staining: (C) ×200. AB: Alcian Blue; MT: Masson’s trichrome; PAS–H: Periodic Acid Schiff–Hematoxylin

Figure 5

Microscopic aspects of the tumor: (A) There is an intense reactivity of the anti-VIM antibody; (B) Intense reactivity of myocytes to α-SMA is observed. Immunomarking with anti-VIM antibody: (A) ×100. Immunomarking with anti-α-SMA antibody: (B) ×200. α-SMA: Alpha-smooth muscle actin; VIM: Vimentin

Figure 6

Microscopic aspects of the tumor: (A) Cells that have undergone mutations in the p53 tumor suppressor gene, immunolabeled in brown; (B) Heavily reactive tumor cells are observed at p16, suggesting a high degree of inactivation of the tumor suppressor gene CDKN2A and an increase in the degree of tumor aggressiveness; (C and D) The density of cells in cell division, stained in brown, is observed. Immunomarking with anti-p53 antibody: (A) ×100. Immunomarking with anti-p16 antibody: (B) ×100. Immunomarking with anti-Ki67 antibody: (C) ×200; (D) ×400. CDKN2A: Cyclin-dependent kinase inhibitor 2A

Figure 7

Microscopic aspects of the tumor: (A) The cellular reactivity that demonstrates the process of protein activation of CDK enzymes required by the cell is observed; (B) The poor intratumoral vascular density is observed by staining (in brown) the capillary endothelium. Immunomarking with anti-cyclin D1 antibody: (A) ×100. Immunomarking with anti-CD34 antibody: (B) ×100. CD34: Cluster of differentiation 34; CDK: Cyclin-dependent kinase

Figure 8

Microscopic aspects of the tumor: (A) Moderate reactivity of cells with the presence of the CD117 transmembrane protein; (B) Cellular reactivity for desmin is observed, a fibrous protein that enters the cytoskeleton of muscle cells, demonstrating the involvement of myocytes in the tumor process. Immunomarking with anti-CD117 antibody: (A) ×100. Immunomarking with anti-desmin antibody: (B) ×100. CD117: Cluster of differentiation 117

Figure 9

Microscopic inflammatory aspects involved in tumor development: (A) The increased number of macrophages present in the tumor mass is observed; (B) The mast cells involved in the tumor mass are identified; (C) B-lymphocytes in low numbers, present in the tumor mass, as an adaptive humoral response; (D) T-lymphocytes involved in intratumoral cellular immunity have been identified. Immunomarking with anti-CD68 antibody: (A) ×100. Immunomarking with anti-tryptase antibody: (B) ×100. Immunomarking with anti-CD20 antibody: (C) ×100. Immunomarking with anti-CD3 antibody: (D) ×200. CD: Cluster of differentiation