Coexistence of Cervical Leiomyosarcoma and Gastric-Type Adenocarcinoma In Situ with Extensive Extension to the Endometrium and Fallopian Tube

Cervical leiomyosarcoma is known to be rare from the previous reviews of a large number of malignant cervical tumors. The patient was a 66-year-old woman with irregular vaginal bleeding. She underwent modified radical hysterectomy and bilateral salpingooophorectomy. Histopathologically, we diagnosed the coexistence of uterine cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ with endometrial lesions that had continuous and skip patterns and fallopian tubal lesions with a partial lesion. To the best of our knowledge, cases of synchronous leiomyosarcoma and cancers have not often been reported; only two cases of synchronous cervical leiomyosarcoma and cervical squamous cell carcinoma have been published. This case is the first presentation of coincidental primary cervical leiomyosarcoma and cervical gastric-type adenocarcinoma in situ. Additionally, we considered cervical gastric-type adenocarcinoma in situ with continuous lesions on the endometrium and skip lesions on the left fallopian tube.


Introduction
Cervical sarcoma is a rare neoplasm; Wright et al. reported that among 1583 patients with cervical malignancies, eight cervical sarcomas were identified, and only one patient had leiomyosarcoma [1]. Thereafter, Khosla et al. reported similar findings in 1804 patients with cervical malignancies; eight cervical sarcomas were identified, and three patients had leiomyosarcoma [2]. Cervical leiomyosarcoma is extremely rare; only six cases have been reported, only two of which were synchronous endocervical leiomyosarcoma and endocervical squamous cell carcinoma [3][4][5][6][7].
To the best of our knowledge, synchronous occurrence of leiomyosarcoma and adenocarcinoma in the cervix has not been reported.
Here, we reported the first case with synchronous occurrence of leiomyosarcoma and adenocarcinoma in situ in the cervix. Moreover, in our case, synchronous occurrence of intraepithelial carcinoma was observed in the endometrium and fallopian tube.

Clinical Course.
The patient, a 66-year-old gravida onepara one woman, was referred to Juntendo University Nerima Hospital with irregular vaginal bleeding and watery vaginal discharge. The hydrometra, with a diameter of approximately 14 × 11 cm by ultrasound examination, was found. Diffusion weighted magnetic resonance imaging revealed an abnormal mass with a diameter of approximately 2 cm on the left sidewall of the uterine corpus without any lymph node enlargement (Figure 1(a)). Fluorodeoxyglucosepositron emission tomography showed abnormal uptake in the mass with a maximal standardized uptake value (SUV, max) of 7.79 (Figure 1(b)). Serum tumor markers, including CEA, CA19-9, and CA125, were within normal limits.  Histological examination of the endometrial biopsy established the diagnosis of leiomyosarcoma and atypical endometrial epithelial lesion. A modified radical hysterectomy and bilateral salpingooophorectomy were performed. After the surgery, the patient was not treated with additional treatments. She had no recurrence within seven months after the operation.

Pathological Finding of Resected Tissues.
In the uterus, a 1.5 cm sized brownish mass was found in the cervix near the corpus; it was located in the stroma with an irregular border. The lumen of the corpus was expanded, and the mucosa was diffusely irregular. There was no nodule or tumorous mass in the corpus. There were no abnormal findings in the bilateral adnexa ( Figure 2).
Histologically, the cervical mass was highly cellular and consisted of densely packed spindle-shaped to oval-shaped cells with high-grade atypia with a fascicular patterned arrangement and occasional lymphocytic infiltration. It infiltrated beneath the mucosa (Figures 3(a) and 3(c)). High mitotic activity and focal necrosis with hemorrhage were also noted in the mass (Figure 3(b)). Immunohistochemically, the spindle and oval cells were positive for vimentin, SMA, and H-caldesmon (Figure 3(d)) and were negative for epithelial Table 1: Immunohistochemical results of the endocervical tumor.
markers and ALK (Table 1). From the histological findings and immunohistochemical results, the mass was finally diagnosed as leiomyosarcoma. Furthermore, irregularity of the epithelium was noted in the cervical mucosa and endometrium. Histologically, atypical epithelial and glandular cells with nuclear irregularity, variable sizes, mitosis, and apoptosis and without stromal invasion were noted in the cervix. Part of the glands had abundant pale eosinophilic cytoplasm, and part of the glands had intestinal differentiation with goblet cells ( Table 2). Similar intraepithelial carcinoma cells were present in the endometrium as continuous and skip patterns and in the left fallopian tube as a partial lesion. Stromal invasion was noted in all lesions (Figures 4(c) and 4(d)). In the cervix and endometrium, mucinous metaplasia and stratified mucinous-producing intraepithelial lesion (SMILE) was admixed with intraepithelial carcinoma lesions (Figures 4(e) and 4(f)). In the left tube, atypical epithelial cells that had less atypia compared with carcinoma were admixed.
Case Reports in Pathology

Discussion
Synchronous gynecological cancers are rare [8][9][10]. From the detailed literature reviews of uterine sarcoma with synchronous occurrence of carcinoma as indicated in Table 3, the present case is the first case with synchronous occurrence of leiomyosarcoma and adenocarcinoma in situ in the cervix [3][4][5][6][7]. Concerning the diagnosis of leiomyosarcoma, three differential diagnoses were considered: leiomyosarcoma, inflammatory myofibroblastic tumor (because these lesions had lymphocytic infiltration), and carcinosarcoma (because focally spindle atypical cells and epithelial lesions were very close). We denied the possibility of an inflamed myofibroblastic tumor because the lesion had high-grade cellular atypia and high mitotic activity and was ALK negative, and we denied the possibility of carcinosarcoma as a result of the absence of a carcinomatous element within the sarcoma lesion. Leiomyosarcoma was finally diagnosed from histological appearances and positive H-caldesmon results, although desmin was negative. However, in the present case, gastric-type AIS (gAIS) was noted in the cervix, endometrium, and tube. Most endocervical glandular malignancies and their precursors are associated with high-risk human papilloma virus (HPV); however, some endocervical glandular gastric-type lesions were not associated with HPV. In the 2014 World Health Organization (WHO) classification, malignancies and their precursors of gastric-type cervical lesions, including lobular endocervical glandular hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA), and gastric-type adenocarcinoma (GAS), were listed as endocervical lesions with a gastric phenotype [11,12]. In particular, GAS is defined as a neoplasm composed of cells with abundant pale or eosinophilic cytoplasm and distinct cell borders, and it is considered that a precursor of GAS is gAIS. gAIS is defined as preexisting endocervical glands that are replaced by atypical columnar cells with abundant pale to eosinophilic cytoplasm and distinct cell borders without lobular architecture. Immunohistochemically, the glandular cells are focally positive for MUC6 and/or HIK1083 and sometimes diffusely positive for p53. ER and PgR are negative, and p16 is usually negative [13]. The classification of gastric-type cervical lesions has been established; the cases previously diagnosed as cervical type mucinous adenocarcinoma may be included in GAS and gAIS; there is a high probability that case reports will increase in the future [14]. Our case was diagnosed as endocervical gAIS from histological features and immunohistochemical results. In addition, synchronous occurrence of intraepithelial carcinoma was also noted in the endometrium with continuous Case Reports in Pathology  and skip patterns and in the tube with partial lesions. Talia et al. reported nine cases in total; of these, three cases had intraepithelial spreading to endometrium [15]. We compared our case with these three cases of gAIS with intraepithelial spreading to the endometrium (there was extension to the lower segment, and, in two cases, there was involvement of the endometrium in the lower corpus with continuous lesions) ( Table 4). Our case not only had continuous lesions to the endometrium but also had tubal skip lesions that were confirmed by continuous sectioning (Figure 6). However, because the tubal skip lesions were similar to other lesions, we suggested that these lesions were most likely not multifocal lesions but a series of lesions.

Conclusion
This is the first report of coincidental primary cervical leiomyosarcoma and cervical gastric-type AIS with intraepithelial spreading to the corpus and fallopian tube.