Adenosarcoma of uterus characterized by differentiation of rhabdomyosarcoma and chondrosarcoma: A case report and review of literature

Abstract

Although Müllerian adenosarcoma of the uterus shows weak malignant potential, there are still some factors indicating a worse prognosis. An incontinuous pelvic pain with urinary frequency, urgency, and hypouricemia arose in a mid-70s woman who refused to acknowledge the history of Tamoxifen use. A huge mass in the pelvis was found simultaneously by palpation, B-ultrasonography, and computed tomography. After a total hysterectomy was performed, a mass with a size of 10.5 cm × 8.5 cm × 8.5 cm was seen at the fundus of the uterus. The tumor consisted of a few benign epithelia and the majority of sarcomas, which mainly contained rhabdomyosarcoma and chondrosarcoma, and a small proportion of endometrial stromal sarcoma. Multifocal necrosis was noticed while the superficial muscular layer of the uterus was invaded. So Müllerian adenosarcoma of the uterus was given to the patient. Eight months after the operation, the patient died from respiratory failure due to pulmonary metastasis. It is suggested that sarcomatous overgrowth, the presence of heterologous elements, especially rhabdomyosarcoma and chondrosarcomatous, myoinvasion, and necrosis, may be histological factors indicating an adverse prognosis.

Introduction

Uterine sarcomas are relatively rare tumors that account for ∼1%–3% of female genital tract malignancies and 3%–7% of uterine tumors. ¹ Uterine adenosarcoma, also known as Müllerian adenosarcoma, is a variety of mixed Müllerian tumor of the uterus and accounts for 8% of sarcomas of the uterus. ² Weak malignancy potential, late-onset local recurrence (25%), rare metastasis, and a high incidence in old women are considered to be typical biological features of Müllerian adenosarcoma of the uterus. Although occasionally presenting in younger women of reproductive age with a desire for future fertility,^3,4 it is most frequently diagnosed in postmenopausal women. ⁵ Postmenopausal bleeding is the most common symptom. Adenosarcomas stage I without sarcomatous overgrowth have a rather good prognosis, with a 5-year overall survival up to 80%. ⁶ However, sarcomatous overgrowth, which is defined as the presence of pure sarcoma occupying at least 25%, makes this tumor transform into a high-grade sarcoma. ⁷ Recurred lesion is often found in the vagina and pelvis (60%). ⁸ A case of Müllerian adenosarcoma of the uterus was diagnosed in our hospital, but died soon after the operation. The case is presented, and some factors probably involved in the poor prognosis are discussed.

Case report

An incontinuous pelvic pain arose in a mid-70s woman (G₄P₄) 25 days before hospitalization, accompanied by urinary frequency, urgency, and hypourocrinia. Without treatment, the patient's condition deteriorated gradually. As far as anamnesis was concerned, cholecystectomy was performed 12 years ago because of cholecystolithiasis. And since hypertension was diagnosed 10 years ago, the blood pressure has been controlled at a normal level by the use of nifedipine (5 mg, bid). As for menstrual and reproductive history, age of menarche was 14, while menopause was 55, with a menstrual cycle of 25–28 days and lasting for 3–5 days. The patient had four pregnancies and four offspring. The history of abnormal menorrhagia was denied. At the time of hospitalization, pulse was 80 times per minute and blood pressure was 22/12 kPa. Physical examination, the extensibility of the vagina was poor, and the cervix was atrophied. A huge mass was felt in the lower right part of the belly. Blood routing tests showed that RBC was 5.22 × 10¹²/L (reference value 3.5–5.5) with WBC 6.2 × 10⁹/L (4–10), PLT 65 × 10⁹/L (100–300), and HGB 135G/L (110–150). Biochemical examination showed that serum albumin was 34.3 (37–53) g/L with fasting plasma glucose 13.03 mmol/L (3.9–6.1), serum uric acid 620 µmol/L (150–430), serum calcium 2.02 mmol/L (2.1–2.6), and serum potassium 3 mmol/L (3.5–5.3). Tumor marker tests showed that CA125 was 35 µg/mL (0–30) with TSGF < 64 µg/mL, AFP < 25 µg/L, and CEA< 5 µg/L. A huge mass was found behind the right of the bladder by color Doppler ultrasound. The echo distribution within the mass was uneven, predominantly solid, with irregular low-echo areas interspersed (Figure 1(a)). Evaluation of computed tomography (CT) demonstrated that the mass was solid-cystic with a wall thickness of about 8 cm. Its density was maldistribution, and the borderline was clear while the uterus was undefined (Figure 1(b)). According to the manifestations, auxiliary examinations, and laboratory inspections, the malignancy of the right ovary or fallopian tube or broad ligament, or uterus was given by a multiple-disciplinary team (MDT). Then, exploratory laparotomy and total hysterectomy were performed. The consent to treatment from the patient was signed.

Figure 1.

Imaging examination demonstrated that a huge mass was located behind the right side of the bladder. (a) Hypogastric color Doppler ultrasound. The echo distribution within the mass was uneven, predominantly solid, with irregular low-echo areas interspersed. (b) Computed tomography (CT) of the pelvic cavity. The mass density was maldistribution, and the value of CT was 19–22 HU. The borderline of the uterus was unclear.

The total hysterectomy was sent for pathological examination. Grossly, a huge mass with a size of 10.5 × 8.5 × 8.5 cm³ was found inside the cavity of the uterus. This tumor protruded from the bottom and showed a wide base, with an incomplete amicula and a henna to gray appearance. On its cross section, the tumor was soft but fragile and looked like rotted fish (Figure 2).

Figure 2.

Gross features of the tumor. A huge mass with a size of 10.5 × 8.5 × 8.5 cm³ was seen inside the cavity of the uterus and protruded from the bottom.

Histologically, HE staining showed that the tumor was mainly made up of malignancies, with only a few benign glands scattered around (Figure 3). The epithelium of the gland was endometrial or cervical mucinous type (Figure 3(a)). Malignancies included rhabdomyosarcoma (RMS, about 35%), chondrosarcoma (CS, about 30%), and endometrial stromal sarcoma (ESS, 25%). RMS cells were astro-like, round, spindle-shaped, dry-pipe-like, girdle-shaped, cobweb-like, and plasmodium-like, with acidophilic cytoplasm and dissymmetry nuclei (Figure 3(b)). Tightly squeezed CS cells were poorly differentiated, with one nucleus, two nuclei, or a huge nucleus. Most extracellular area was full of hyaline cartilage-like matrix (Figure 3(c)). As far as ESS was concerned, cellular atypia was much more obvious, and pathologic caryokinesis was easily found (> 6/high power field) (Figure 3(d)). So ESS was classified as high-grade. Moreover, fatty tissue metaplasia and mucoid degeneration were also found among RMS, CS, and ESS cells. Multifocal necrosis was noticed. The superficial muscular layer of the uterus was invaded.

Figure 3.

Histological features of the tumor are shown by HE staining, × 100. (a) The epithelium of the endometrial gland was benign. (b) Rhabdomyosarcoma (RMS) cells were pleomorphic with acidophilic cytoplasm and dissymmetry nuclei. (c) Tightly squeezed chondrosarcoma (CS) cells were poorly differentiated. (d) Atypia of endometrial stromal cells was much more obvious.

Other microscopic features were observed. Several small tumors, which had been found in the mucosa surrounding the huge mass and among uterine muscles by color Doppler ultrasound and CT, were turned out to be composed of leiomyoma cells with hyaline degeneration and fatty degeneration. No obvious lesions were seen on the two sides of the adnexa uteri. Then the same pathological diagnosis, Müllerian adenosarcoma of the uterus, was given to this huge mass by three experienced pathologists, respectively.

Epithelium of glands in the tumor was positive upon the immune detection of low molecular cytokeratin (Figure 4(a)). RMS cells were positive for desmin (Figure 4(b)), myoglobin detection (Figure 4(c)), and negative for vimentin (Figure 4(d)). ESS cells were positive upon CD10 detection (Figure 4(e)). Ki67 was about 75% (Figure 4(f)).

Figure 4.

Immunophenotypes of the tumor. (a) Epithelium of glands was positive for low molecular cytokeratin, × 100. (b) Rhabdomyosarcoma (RMS) cells were positive for desmin, × 200. (c) RMS cells were positive for myoglobin, × 200. (d) RMS cells were negative for vimentin, × 200. (e) Endometrial stromal sarcoma (ESS) cells were positive for CD10, × 200. (f) Ki67 was about 75%, × 200.

At the follow-up 1 year after surgery, it was learned that the patient had died 8 months after surgery from respiratory failure led by “lung metastasis,” according to CT examination at the local hospital in another city (imaging figures unavailable). No lung biopsy or autopsy was performed. The reporting of this study conforms to CARE guidelines. ⁹ The consent to publish was signed by the patient's legally authorized representative. We have de-identified all patient details.

Discussion

Uterine adenosarcoma was first reported by Clement and Scully, ¹⁰ and the term Müllerian adenosarcoma has become universally recognized since a few cases were added to the original series in 1979. ¹¹ As a rare biphasic malignant mesenchymal tumor, uterine adenosarcoma is composed of a benign glandular component and a malignant, but generally low-grade, stromal component. ¹² The molecular pathogenesis of this tumor, however, remains to be elucidated. Some studies suggest that tamoxifen may play a role in the pathogenesis of adenosarcoma.^13–16

Although the uterine corpus is by far the most common primary site, adenosarcoma may also arise in the cervix, ¹⁷ ovary, fallopian tube, or vagina. ¹⁸ Adenosarcoma occurring outside the female genital tract likely represents tumors arising from pre-existing endometriosis.^19–21 Uterine adenosarcoma affects women of a broad age range. The incidence is highest in perimenopausal or postmenopausal women, but cases have been reported in children as young as 10 years. ²² Patients may present clinically with abnormal vaginal bleeding and/or pelvic pain or, in a large percentage of cases, with no symptoms or only with a mass in the pelvic cavity.

Surgery, chemotherapy, radiotherapy, and hormone therapy are standard treatments according to the guidelines of the National Comprehensive Cancer Network (NCCN). Surgical resection is the most commonly used method involving a total hysterectomy and bilateral salpingo-oophorectomy, and dissection of pelvic and iliac lymph nodes will be performed if there are poor prognostic factors, ⁷ just like what has been done in our case. Chemotherapy shows some effect on patients after surgery or those who cannot be cured by hysterectomy. The combinations of gemcitabine/docetaxe, doxorubicin/ifosfamide, doxorubicin/cisplatin, cisplatin/ifosfamide, and carbo/paclitaxel are the chemotherapy agents widely used.^23,24 However, only tumors with sarcomatous overgrowth could benefit from adjuvant chemotherapy. ²⁵ Regrettably, the patient in our case refused the adjuvant chemotherapy or radiotherapy.

Adenosarcoma is of generally low malignant potential, except when accompanied by sarcomatous overgrowth and myoinvasion. Sarcoma component originates from the stromal of the uterus (homologous) and /or differentiates towards elements not typically found in the uterus (heterologous). Sarcomatous overgrowth (SO) and the presence of heterologous elements are found in about 10–15% of cases.^26–28 Typically, rhabdomyosarcomatous differentiation is the most common. ¹ Because uterine adenosarcoma with sarcomatous overgrowth (ASSO) has a malignant potential more similar to that of high-grade sarcoma, ²⁹ sarcomatous overgrowth has received a lot of attention. At present, it is defined as the presence of pure sarcoma occupying at least 25% of the tumor, usually high grade in nature, and without a benign glandular component. ⁷ The reported prevalence of sarcomatous overgrowth in patients with uterine adenosarcoma varies greatly, from 8% to 65%.^29,30 Given the aggressive nature of ASSO, local excision alone is insufficient, and thorough resection with negative margins may be beneficial for young, early staged patients. ³¹ Recurrent disease has been reported to occur in 26%–40% of all patients with uterine adenosarcoma after primary therapy. ³² However, patients with sarcomatous overgrowth have a much higher reported rate of recurrence (70%–82%). ²⁹

Conclusion

It is suggested that the pathogenesis of some uterine adenosarcomar cases may not be associated with tamoxifen use, and that sarcomatous overgrowth, the presence of heterologous elements, especially rhabdomyosarcoma and chondrosarcomatosis, muscular invasion, and necrosis, may be histological factors indicating adverse prognosis.