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

1. 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 [3-7].

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.

2. Case Presentation

2.1. Clinical Course. The patient, a 66-year-old gravida one-para 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 x 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)). Fluorodeoxyglucose-positron 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.

2.2. 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 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 (Figures 4(a) and 4(b)). These findings led to the diagnosis of adenocarcinoma in situ (AIS). The carcinoma cells consisted mostly of gastric-type cells and partly of intestinal type cells from the histological features and immunohistochemical findings (Figures 5(a) and 5(b), 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.

3. Discussion

Synchronous gynecological cancers are rare [8-10]. 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 [3-7]. Concerning the diagnosis of leiomyosarcoma, three differential diagnoses were considered: leiomyosarcoma, inflammatory myofibroblasts 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 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.

4. 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.

https://doi.org/10.1155/2018/5848629

Conflicts of Interest

The authors declare that there are no conflicts of interest.

References

[1] J. D. Wright, K. Rosenblum, P. C. Huettner et al., "Cervical sarcomas: An analysis of incidence and outcome," Gynecologic Oncology, vol. 99, no. 2, pp. 348-351, 2005.

[2] D. Khosla, R. Gupta, R. Srinivasan, F. D. Patel, and A. Rajwanshi, "Sarcomas of uterine cervix: Clinicopathological features, treatment, and outcome," International Journal of Gynecological Cancer, vol. 22, no. 6, pp. 1026-1030, 2012.

[3] B. Wiston, J. Gerale, and C. Sheldon, "Coincidental primary srcoma and carcinoma of the cervix, report of two cases," Obstetrics and Gynecology, vol. 33, no. 1,1969.

[4] K. Dudzik, A. Krzysteczko, L. Kolny, A. Bak, E. Stawicka-Ociepka, and K. Nowosielski, "Synchronous uterine adenocarcinoma and leiomyosarcoma--A case study," Przeglqd Menopauzalny, vol. 16, no. 1, pp. 23-25, 2017.

[5] K. Katie, C. Eric, and A. Edwin, "Synchronous uterine adenocarcinoma and leiomyosarcima: a rare case report causing a clinical conundrum," International Journal of Surgery Case Reports, vol. 22, pp. 32-34, 2016.

[6] A. Isin Dogan Ekici, T. Kucukali, M. Coskun Salman, and A. Ayhan, "Triple simultaneous primary gynecological malignancies in a 56-year-old patient," International Journal of Gynecological Cancer, vol. 16, no. 5, pp. 1947-1950, 2006.

[7] I. Sheyn, J. L. Mira, R. Blanco et al., "Concomitant well-differentiated adenocarcinoma and leiomyosarcoma of the uterus," Archives of Pathology & Laboratory Medicine, vol. 124, pp. 1539-1541, 2000.

[8] B. Saatli, N. Yildirim, A. Ozay, M. Koyuncuoglu, B. Demirkan, and U. Sayg?l?, "Synchronous tumors of the female genital tract: a 20-year experience in a single center," Polish Gynaecology, vol. 85, no. 6, pp. 441-445, 2014.

[9] S. Y. Tong, Y. S. Lee, J. S. Park et al., "Clinical analysis of synchronous primary neoplasm of the female reproductive tract," European Journal of Obstetrics & Gynecology and Reproductive Biology, vol. 136, pp. 78-82, 2008.

[10] C. Amalinei, R. Balan, E. Crauciuc, and O. Toma, "Synchronous, metachronous and metastatic tumoes of the upper female genital tract," Annals of the "Alexandru loan Cuza" University, Sect. II a, Genetics and molecular biology, vol. 9, pp. 1-22, 2008.

[11] G. D. Zielinski, P. J. F. Snijders, L. Rozendaal et al., "The presence of high-risk HPV combined with specific p53 and p16INK4a expression patterns points to high-risk HPV as the main causative agent for adenocarcinoma in situ and adenocarcinoma of the cervix," The Journal of Pathology, vol. 201, no. 4, pp. 535-543, 2003.

[12] R. J. Kurman, M. L. Carcangiu, C. S. Herrington, and R. H. Young, WHO classification of tumors of female reproductive organs, IARC, Lyon, France, 2014.

[13] Y. Mikami and W. G. McCluggage, "Endocervical glandular lesions exhibiting gastric differentiation: an emerging spectrum of benign, premalignant, and malignant lesions," Advances in Anatomic Pathology, vol. 20, no. 4, pp. 227-237, 2013.

[14] A. Kojima, Y. Mikami, T. Sudo et al., "Gastric morphology and immunophenotype predict poor outcome in mucinous adenocarcinoma of the uterine cervix," The American Journal of Surgical Pathology, vol. 31, no. 5, pp. 664-672, 2007.

[15] K. L. Talia, C. J. R. Stewart, B. E. Howitt, M. R. Nucci, and W. G. McCluggage, "HPV-negative Gastric Type Adenocarcinoma in Situ of the Cervix," The American Journal of Surgical Pathology, vol. 41, no. 8, pp. 1023-1033, 2017.

Ayako Urass (iD), (1) Kanako Ogura, (1) Asumi Sakaguchi, (1) Hiroko Onagi, (1) Daiki Ogishima (iD), (2) Yayoi Sugimori, (2) Kensuke Hamamura, (2) Masaharu Fukunaga, (3) and Toshiharu Matsumoto (1)

(1) Department of Diagnostic Pathology, Juntendo University Nerima Hospital, Tokyo, Japan

(2) Department of Gynecology, Juntendo University Nerima Hospital, Tokyo, Japan

(3) Department of Diagnostic Pathology, Shin-Yurigaoka General Hospital, Kanagawa, Japan

Correspondence should be addressed to Ayako Ura; a-ura@juntendo.ac.jp

Received 17 November 2017; Accepted 22 January 2018; Published 18 February 2018

Academic Editor: Yoji Nagashima

Caption: Figure 1: (a) Diffusion weighted magnetic resonance imaging. The abnormal signal with a diameter of approximately 2 cm on the left sidewall of the uterine corpus (at indicated by arrow). (b) FDG-PET. Abnormal uptake in the tumor had a maximal standardized uptake value (SUV (max)) of 7.79.

Caption: Figure 2: The specimen from the operation. There was a 1.5 cm brownish mass with an unclear border with the stroma on the uterine corpus side of the cervix.

Caption: Figure 3: Endocervical tumor. (a) H-E stain. Fascicular and interlacing proliferation of spindle cells with hemorrhage. (b) H-E stain. Spindle cells had high-grade atypia and active mitosis. (c) H-E stain. Atypical cells were infiltrating just beneath the mucosa. (d) Immunohistochemical stain of H-caldesmon. Tumor cells were diffuse positive.

Caption: Figure 4: Intraepithelial lesions. (a) H-E stain. Endocervical lesions. Neoplastic epithelium replaces normal epithelium on the cervical surface and glands. (b) Neoplastic epithelium with atypical epithelial and glandular cells with nuclear irregularity, variable sizes, mitosis, and apoptosis. Some glands have abundant pale eosinophilic cytoplasm, and partial glands have intestinal differentiation with goblet cells. AIS. (c) H-E stain. Endometrial lesions. Similar lesions in the endocervical mucosa. Cytological atypia was less than Figures 4(a) and 4(b); however they have mild nuclear atypia and pseudostratification. (d) H-E stain. The left tube mucosa is abnormal with mild nuclear pseudostratification, hyperchromasia, and enlargement, and tumor cells had mitosis. However, dysplasia was less than AIS. (e) H-E stain. Endometrium without lobular architecture and with the characteristic "pale pink" cytoplasm that was next to AIS. Simple gastric metaplasia (as indicated by arrow). (f) H-E stain. The endometrium showed lesions of stratified mucin-producing intraepithelial lesion (SMILE) focally. The stratified epithelium contains cells with mucin vacuoles in all cell layers. Nuclear atypia and hyperchromasia figures are present.

Caption: Figure 5: Immunohistochemical results. (a) MUC6 stain. Tumor cells were partially positive. (b) HIK1083 stain. Tumor cells were focally positive.

Caption: Figure 6: Distribution of epithelial lesions. Blue: gAIS. Red: simple gastric metaplasia. Green star: SMILE. The tubal lesion is a skip lesion. Cervical leiomyosarcoma is indicated by arrows.
Table 1: Immunohistochemical results of the endocervical tumor.

AE1/AE3        -
CAM5.2         -
34BE12         -
EMA            -
Vimentin       +
SMA            +
Desmin         -
H-caldesmon    +
CD10           -
ALK            -
Ki-67         10%

Table 2: Immunohistochemical analysis for each epithelial lesion.

Lesions                       p53     p16   MUC2     MUC6     HIK1083

AIS (endocervical)          Focal +    -     -     Partial+   Focal +
AIS (endometrium)           Focal +    -     -     Partial+   Focal +
Simple gastric metaplasia      -       -     -     Partial+   Focal +
SMILE                       Focal +    -     -        -          -
Tube                          ND      ND     ND    Partial+   Focal +

Lesions                     Ki-67   p40

AIS (endocervical)           80%    ND
AIS (endometrium)            70%     -
Simple gastric metaplasia    50%     -
SMILE                        40%     +
Tube                         40%    ND

ND, not done.

Table 3: Cases of synchronous primary malignant neoplasms: a
summarizing review of the references.

case     Reference      Age    Location of          Other cancers
                              leiomyosarcoma

(1)    Winston et al.   77    Uterine cervix   Squamous cell carcinoma
                                                  of uterine cervix

(2)    Winston et al.   53    Uterine cervix   Squamous cell carcinoma
                                                  of uterine cervix

(3)    Dudzik et al.    60    Uterine corpus        Endometrioid
                                                adenocarcinoma, G2 of
                                                   uterine corpus

(4)     Kaite et al.    60    Uterine corpus        Endometrioid
                                                adenocarcinoma, G2 of
                                                 uterine corpus, and
                                                  bilateral serous
                                                  cystadenofibromas

(5)     Isin et al.     56    Uterine corpus     Well-differentiated
                                                  ovarian mucinous
                                               cystadenocarcinoma and
                                                    endometrioid
                                                adenocarcinoma, G1 of
                                                   uterine corpus

(6)     Sheyn et al.    66    Uterine corpus        Endometrioid
                                                adenocarcinoma, G1 of
                                                   uterine corpus

(7)       Our case      66    Uterine cervix        Gastric type
                                               adenocarcinoma in situ
                                                  of uterine cervix

TC, tunnel cluster; TZ, transformation zone; LEGH, lobular
endocervical glandular hyperplasia; SGM, simple gastric metaplasia;
SMILE, stratified mucin-producing intraepithelial lesion.

Table 4: Cases of gastric type AIS with intraepithelial spreading to
the endometrium: a summarizing review of the references.

Case    Reference     Age    Location of AIS     Form of AIS type

(1)    Karen et al.   61     Proximal to TZ,     Mixed gastric and
                              lower uterine       intestinal type
                              segment, and
                               endometrium

(2)                   73    TZ, lower uterine    Mixed gastric and
                              segment, and        intestinal type
                               endometrium

(3)                   52      TZ and lower      Purely gastric type
                             uterine segment

(4)      Our case     66      Whole cervix,      Mixed gastric and
                            endometrium, and      intestinal type
                            focally left tube

Case   Histological subtype    Other findings
       of epithelial lesions

(1)            None                 None

(2)             SGM                 None

(3)          TC, LEGH               None

(4)         SMG, SMILE            Cervical
                               leiomyosarcoma
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Title Annotation:Case Report
Author:Urass, Ayako; Ogura, Kanako; Sakaguchi, Asumi; Onagi, Hiroko; Ogishima, Daiki; Sugimori, Yayoi; Hama
Publication:Case Reports in Pathology
Geographic Code:9JAPA
Date:Jan 1, 2018
Words:2470
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