Turkish Journal of Pathology

Türk Patoloji Dergisi

Turkish Journal of Pathology

Turkish Journal of Pathology

2007, Vol 23, Num, 2     (Pages: 082-086)

Histogenesis of lipomatous component in uterine lipoleiomyomas

Filiz BOLAT 1, Fazilet KAYASELÇUK 1, Tuba CANPOLAT 1, Serkan ERKANLI 2, İlhan TUNCER 1

1 Baskent University Faculty of Medicine, Department of Pathology, ANKARA
2 Baskent University Faculty of Medicine, Department of Gynecology and Obstetrics, ANKARA

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Summary

Uterine neoplasms composed of an admixture of smooth muscle and adipose tissue are rare and have been designated as lipoleiomyomas. The origin of this tumor is stil controversial and it has not been sufficiently studied. The aim of our study was to investigate the immunohistochemical phenotype of fat cells in uterine lipoleiomyomas so as to clarify their origin. Archived tissue samples of 10 uterine lipoleiomyomas were selected and analyzed immunohistochemically for vimentin, desmin, and HMB-45 expression. The patients ranged from 31 to 63 years of age (mean age 53.5±9.9). Seven tumors which affected the uterine corpus, showed intramural location; while two cases were subserosal, and one was in the cervix. All tumors were constituted by irregular bundles of smooth cells and mature large adipose cells. The amount of adipose component varied from 5 to 95% of the tumor mass. Cytological atypia and necrosis were not seen. Immunohistochemical investigations revealed obvious reactivity to vimentin and desmin in perivascular immature mesencyhmal cells and tumoral smooth muscle cells. Adipose cells in the tumors demonstrated uniform vimentin expression and inconsistent desmin immunoreactivity. All adipose cells were negative for HMB-45 antigen. However, HMB-45 antigen was weakly positive in spindle shaped tumor cells of two cases. In our study, the immunohistochemical findings suggest a complex histogenesis for these tumors, which may arise from perivascular immature mesencyhmal cells or direct transformation of smooth muscle cells into adipocytes by means of progressive intracellular storage of lipids.

Introduction

Uterine lipoleiomyoma is a rare mesencyhmal neoplasm and mostly described as a variant of uterine leiomyoma. They constitute less than 0.2% of benign uterine tumors[1-6].

The other nomenculatures for this tumor are fibrolipoleiomyoma, benign mixed mesodermal tumor, lipomatous tumor, and so on[3]. Since most cases are not referred due to their benign behaviour and also in most circumstances the fat component represents a more or less abundant cell population in the context of common leiomyomas of the uterus their precise incidence is unknown[1,4]. These tumors usually occur in postmenopausal women between 50 and 75 years of age. Many of these patients are asymptomatic, but in some patients symptoms are similar to those of uterine leiomyomas, such as pelvic discomfort, heaviness, and pressure, or vaginal bleeding[1,4,7].

Lipoleiomyoma is composed of variable mixture of smooth muscle and mature adipose tissue. Sometimes this tumor is accompanied by anomalous blood vessels surrounded by smooth muscle cells, and it is termed angiomyolipoma, eg. renal angiomyolipoma (RAML)[8]. Although the histogenesis of RAML is uncertain, it is believed to arise from a pluripotent cell that differentiates into adipocytes and smooth muscle cells, as suggested for lipoleiomyoma[2,8]. Several reports in the literature have documented positive reactivity of HMB-45 for smoothmuscle cells in angiomyolipoma[8]. Furthermore, HMB-45 antigen positivity was described in uterine lipoleiomyoma by Aung et al[2].

The origin of the lipomatous lesions of the uterus has been the subject of much speculation, including misplaced embryonic fat cells, metaplasia of muscle or connective tissue cells into fat cells, lipocytic differentiation of a specific primitive connective tissue cell, perivascular fat cells accompanying the blood vessels into the uterine wall during surgery, or fatty infiltration or degeneration of connective tissue[9].

The aim of the study is to investigate presumptive histogenesis of uterine lipomatous lesions and to present their histological features, and to discuss the possible origin of this lesion.

Methods

We reevaluated 10 cases diagnosed as uterine lipoleiomyomas in Department of Pathology, Adana Baskent University, between 1999 and 2007. We recorded the following parameters: estimated percentage of tumor area involved by adipocytes, presence and degree of atypia of smooth muscle and adipocytes, mitotic rate, and tumor borders (circumscribed versus infiltrative).

The surgical specimens were fixed in 10% neutral-buffered formalin and paraffin embedded. For immunohistochemistry, serial sections of 5-μm-thickness were cut from the paraffin blocks. The sections were deparaffinized with xylene and rehydrated with etanol. Nonenzymatic antigen retrieval was performed on each slide and washed by phosphate-buffered saline. Immunohistochemical staining was performed manually using the standard avitin-biotin-peroxidase complex technique with DAKO (LSAB kit; DAKO, Glostrup, Denmark). The slides were exposed to primary antibodies for vimentin Ab-2 (cloned V9, NeoMarkers, Fremont CA, USA) desmin Ab-1 (Clone D33, dilution 1:50, NeoMarkers, Fremont CA, USA) and HMB-45 (code N1545, LSAB kit; DAKO, Glostrup, Denmark).

Immunoperoxidase staining of smooth muscle cells, adipocytes and perivascular mesencyhmal cells are scored as negative and positive.

Results

During the study period, 707 patients with uterine leiomyomas were identified, and 10 lipoleiomyomas were found. Thus, lipoleiomyomas were found in 1.4% of pateints with uterine leiomyomas.

The patients ranged from 31 to 63 years of age (mean age 53.5±9.9). Five cases were postmenopausal, two were perimenopausal and three cases were in reproductive period. Nine patients sought medical attention for symptomatic leiomyomas (pelvic pain, enlarged uterus, and/or dysmenorrhea). One patient presented for treatment of a gynecological malignancy (endometrial carcinoma).

Gross Pathology
Eight women underwent hysterectomy and bilateral salphingoophorectomy, two myomectomy for a pre-operative diagnosis of leiomyoma. One patient underwent hysterectomy and bilateral salphingoopherectomy and pelvic paraaortic lymph node dissection for endometrial carcinoma. The size of the lipoleiomyomas ranged from 1.5 cm to 19 cm, with a median of 4.75 cm.

Seven tumors affected the uterine corpus, and they were located intramuraly; two cases were subserosal, and one was in the cervix. The gross appearance depended on the amount of fatty component. With microscopic foci of adipose differentiation, the cut surface resembled the usual leiomyoma. In cases with a large amount of fat, the cut surface was yellow and occasionally lobulated (Figure 1).

Figure 1: Gross appearence of lipoleiomyoma with high adipocyte component, showing a yellowish lobulated cut surface.

Histopathological Findings
All lipoleiomyoma cases consisted histologically of smooth muscle tissue admixed with a varying amount of mature adipose tissue. The amount of adipose component varied from 5% to 95% of the tumor mass. In two cases, the tumors consisted largely of mature adipose tissue (95%), and also islands composed of bundles of smooth muscle fibers and fibrous connective tissue were seen among the adipose tissue (Figure 2). In three cases hyaline degeneration was detected. Blood vessels in the stroma were not prominent and showed the usual, thin walled appearance. Cytological atypia (in smooth muscle cells or adipocytes), necrosis, and calcification were not seen. The mitotic rate was zero in all cases. In cases with malignancy no gross or microscopic contiguity between the lipoleiomyoma and the malignancy was observed. None of the tumors had infiltrative margins.

Figure 2: Numerous mature lipocytes between smooth muscle cells in a lipoleiomyoma (HE x100).

Immunohistochemistry
Vimentin and desmin were widely expressed in smooth muscle cells, pericytes, and endothelial cells (Figure 3). Varying degrees of immunoreactivity for vimentin were uniformly detected in fat cell components of all tumors (Figure 4).

Figure 3: Smooth muscle cells in a lipoleiomyoma showing strong vimentin immunoreactivity (x200).

Figure 4: Intense vimentin immunoreactivity in mature lipocytes of lipoleiomyoma (x400).

Tumor cells with adipose feature also demonstrated inconsistent desmin immunoreactivity. The number of desmin-positive tumor cells was variable in various tumors and within different areas of the same tumor.

All adipose cells were negative for HMB- 45 antigen. However, HMB-45 antigen was weakly positive in spindle shaped tumor cells of two cases.

Discussion

Uterine lipoleiomyoma is a rare benign mesencyhmal neoplasm and mostly described as a variant of uterine leiomyoma[1-7]. The reported incidence varies from 0.03% to 0.2%[10]. Lipoleiomyomas can occur anywhere in the uterus or the uterine cervix. They can be subserosal, intramural or submucosal[1,4]. In our cases, seven tumors were in the uterine corpus, and intramural; two cases were subserosal and one of them was in the cervix.

Histolopathologically, three types of uterine tumors with lipomatous component are seen[2,9]: a) Pure lipoma consisting of adipocytes and very few scattered smooth musle cells, b) Lipoleiomyoma with a variable amount and distribution of adipocytes and smooth muscle cells, c) Angiomyolipoma with prominent vascular structures admixed with adipoytes and smooth muscle cells.

The diagnosis of uterine lipomatous tumors is based on the recognition of mature adipocytes. Lipoblast[11] and atypical smooth muscle cells[12] have been reported anecdotally in uterine lipoleiomyomas. The differential diagnosis of similar uterine tumors with adipose tissue and spindle cells include; spindle cell lipoma, angiolipoma, angiomyolipoma, myelolipomas, atypical lipoma, and well-differentiated liposarcomas. In our cases, all lipoleiomyomas were comprised of mature adipocytes and smooth muscle cells. There was neither lipoblastic component, atypia nor necrosis and mitotic activity in adipocytes or smooth muscle cells.

The origin of lipomatous tumors is controversial. Sieinski[5] summarized the different proposed theories in: 1) Misplaced embryonal mesodermal rests with a potential for lipoblastic differentiation, 2) Lipoblast or pluripotential cells migrating along uterine arteries and nerves, 3) Adipose metaplasia of stromal or smooth muscle cells in a leiomyoma.

There are many controversies in the pathogenesis and origin of tumor cells in uterine lipoleiomyoma and angiomyolipomas[5,6,9-11,13].

Our immunohistochemical studies have revealed reactivity of adipocytes for vimentin and desmin confirming the hypothesis of their direct transformation from smooth muscle cells into adipose cells. Furthermore, in our series the presence of vimentin positivity in mesencyhmal cells around the vessels strengthen the neometaplasia of pericapillary pluripotential mesencyhmal cells as Seinski and Resta et al. have suggested[4,5]. In all cases, variable degrees of vimentin and desmin positivity in mature adipocytes might suggest a direct transformation of muscle cells into adipose cells.

Moreover, in our cases neither angimyolipoma like vessels, nor HMB-45 antibody positivity was seen. Just in two cases weak HMB-45 positivity in spindle cells was seen. Yaegashi et al. described a uterine angiomyolipoma, where smooth muscle cells from a tumor area were spindle shaped and negative for HMB-45 antigen[13]. As in literature we found out that uterine and renal angiomyolipomas were different clinical entities, having similarity only in histologic pattern[10].

In conclusion, our study revealed that the histological and immunohistochemical findings suggest a complex histogenesis for these tumors, in that they might arise from mesencyhmal immature cells or from direct transformation of smooth muscle cells into adipocytes by means of progressive intracellular storage of lipids.

Reference

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9) Willen R, Gad A, Willien H. Lipomatous lesions ofthe uterus. Virchows Arch A Pathol Anat Histol 1978; 17; 377:351-361.

10) Prieto A, Crespo C, Pardo A, Docal I, Calzada J, Alonso P. Uterine lipoleiomyomas: US and CT findings. Abdom Imaging 2000;25:655-657.

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12) Lin M, Hanai J. Atypical lipoleimyoma of the uterus. Acta Pathol Jpn 1991;41:164-169.

13) Yaegashi H, Moriya T, Soeda S, Yonemoto Y, Nagura H, Sasano H. Uterine angiomyolipoma: Case report and review of the literature. Pathol Int 2001;51:896-901.

Keywords : Female genital tract, histogenesis, lipoleiomyoma