A unique uterine cervical “teratocarcinosarcoma”: a case report

Carcinosarcoma [1, 2] and teratoma [3, 4] are encountered in the uterine cervix, although rarely. Cervical carcinosarcoma, characterized by a mixture of both malignant epithelial and mesenchymal elements, is an aggressive neoplasm with poor prognosis [1, 2]. Teratomas consist of two or three germ layers: ectodermal, mesodermal, and endodermal components in any combination. Mature teratoma is usually benign, but 1–3% cases can show malignant transformation; immature teratoma consists of embryonic tissue, mainly neural tissue. Cervical teratoma is thought to develop from germ cells that get trapped along their migration during embryonic development [3, 5].

Teratocarcinosarcoma (TCS) has both epithelial components and two or more mesenchymal components, such as cartilage, fibroblasts, muscular, and bony tissues. The tumor, known to arise in the nasal cavity and paranasal sinuses, was first described as a teratoid carcinosarcoma by Shanmugaratnam et al. in 1983 [6], whereas the term TCS was initially proposed by Heffner and Hyamsin in 1984 [7]. Since then, there have been less than 100 cases with tumors originating from the nasal cavity or paranasal sinuses reported in the English literature [8]. The patients were predominantly male (87%) with an average age of 54.5 years [7, 8]. TCS has several clinicopathological features and problems, such as poor prognosis due to rapid growth, many differential diagnoses, and ambiguities of histogenesis or tumor origin. In sinonasal TCS, radical surgery followed by radiotherapy is the most commonly performed treatment option, however, resulting in a poor prognosis (average survival, 1.7 years) due to frequent recurrence and metastasis [7, 8]. Because TCS shows histologically diverse features such as mature/benign as well as immature / malignant epithelial and mesenchymal components, pathologists need to distinguish TCS from carcinosarcoma, immature teratoma, teratoma with malignant transformation, and peripheral primitive neuroectodermal tumor. TCS has been reported to occur in the female reproductive organs, especially in the ovary, other than in the nasal cavity and paranasal sinuses [9‐13]. Ovarian TCS is thought to originate from germ cells [9‐13].

Herein, we report a unique uterine cervical tumor with carcinosarcomatous and teratomatous features, histologically resembling sinonasal TCS.

The present case is a unique cervical cancer, consisting of neuroepithelial components positive for CD99 and synaptophysin, immature / atypical intestinal glands positive for SALL4 and CDX-2, cartilage cells, and rhabdomyosarcoma, resembling sinonasal TCS. There have been less than 100 cases of TCS reported in the literature to date, most of which were observed to occur in the nasal cavity or paranasal sinuses [8], but were also in female reproductive organs, especially the ovary [9‐13] (Table 2). TCS has several differential diagnoses such as carcinosarcoma, immature teratoma, teratoma with malignant transformation, and peripheral primitive neuroectodermal tumor, because of its histological heterogeneity.

Currently, teratomas of the ovary and cervix are thought to have a parthenogenetic origin from the oocyte after completion of the first division [5]. Extragonadal teratoma usually arises in midline structures, such as the sacrococcygeal, mediastinal, and sacral regions, and rarely arises in the uterine cervix [5]. Grayson et al. [2] reported that in 8 cases with uterine cervical carcinosarcoma, HPV was detected in all. However, the present case showed no HPV infection, which was confirmed by the negative reactions of immunohistochemical staining for p16^INK4a and HPV in situ hybridization. Immature teratoma is defined by the presence of neuroepithelial tubules and rosettes. In the present case, however, the tumor predominantly consisted of neuroepithelial tissues, but lacked neuroepithelial tubules or rosettes. In addition, the tumor was immunohistochemically negative for Oct-4, which is usually positive for immature teratoma grade 2/3 [14]. In this case, malignant transformation of mature teratoma could be ruled out because of an absence of continuity between malignant or immature components and mature teratomatous tissues. Peripheral primitive neuroectodermal tumor was considered unlikely because ESWR1 rearrangement was not observed.

In the present case, immature / atypical intestinal glands and neuroepithelium were positive for SALL4, which is known as a sensitive and specific marker of germ cell tumors [15]. This suggests that this tumor is germ cell derived. In the pure mature or immature teratoma, there is the presence of i(12p) and 12p amplification in non-teratoma germ cell components in ovarian or sacrococcygeal tissues [16, 17]. However, this case showed neither i(12p) nor 12p amplification. The absence of cytogenetic abnormalities in this case suggests that the teratomatous components have an analogous histogenesis compared to the pure ovarian teratoma.

The histogenesis of cervical TCS remains to be clarified, but teratoid carcinosarcoma of the ovary has been reported to show components derived from germ cells [9‐13]. Although germ cells are not usually found in the uterine cervix, extragonadal germ cell tumors rarely occur in the uterine cervix [3‐5]. The cases of ovarian TCS showed a poor clinical outcome mainly because they were at the advanced stage. Radical surgical resection followed by radiotherapy is the most common treatment option for sinonasal TCS [7, 8]; therefore, a combination of surgery and radiotherapy may be expected to be effective for the present case with TCS.

This is the first case report of uterine cervical TCS that may have originated from germ cells, but with a histogenetic pathway different from pure mature teratoma of the ovary.