Embryonal rhabdomyosarcoma (sarcoma botryoides) occurs uncommonly, but not rarely, as a primary cervical neoplasm. Affected patients are most commonly in the late teens and early twenties (mean age 18 years), although the age range is relatively wide and much older patients can be affected [3–9]. The usual presentation is vaginal bleeding or a mass protruding from the introitus. There is an association between cervical embryonal rhabdomyosarcomas, ovarian Sertoli-Leydig cell tumors, thyroid goiters, pleuropulmonary blastomas, and some other embryonic neoplasms. This is due to underlying germline DICER1 mutation [10, 11]. Since some studies show that a significant minority of patients (around 20%) with cervical embryonal rhabdomyosarcoma have other DICER1-associated tumors [12], the diagnosis should prompt consideration of the DICER1 syndrome with a careful review of the patient’s personal and family history with genetic studies if appropriate. It is also noteworthy that while most patients with either proven germline DICER1 mutation or DICER1-associated cervical embryonal rhabdomyosarcoma reported in the literature are relatively young (<25 years), occasional cases arise in older women [13] such that older age is not a reliable criterion for excluding DICER1 syndrome in patients with cervical embryonal rhabdomyosarcoma.

Grossly, cervical embryonal rhabdomyosarcoma usually takes the form of a polypoid mass or multiple polyps, which may be totally removed by polypectomy. Occasionally, there is an infiltrative mass without a polypoid architecture, but this is uncommon. The cut surface may be myxoid with areas of necrosis, and some neoplasms have an overtly botryoid (grapelike) gross appearance.

Histological examination usually shows a polypoid lesion covered by a variety of types of benign glandular Mullerian-type epithelium, sometimes with focal squamous differentiation (Fig. 10.2a). Glands may also be present deep within the core of the neoplasm. The features of malignancy may be subtle in that, in large part, the stroma can be hypocellular and myxoid or edematous. However, tightly packed hypercellular foci are also present which sometimes coalesce to form large cellular aggregates. There is usually mitotic and apoptotic activity within the cellular foci (Fig. 10.2b). Characteristically there is increased cellularity around the glandular elements, resulting in a cambium layer, and here mitotic figures and apoptotic bodies are usually apparent. Most of the stromal cells have small hyperchromatic nuclei with scant cytoplasm and delicate cytoplasmic processes, but cells with larger nuclei and an almost epithelioid appearance may be present. Cells with more abundant eosinophilic cytoplasm and cytoplasmic cross striations may also be identified (Fig. 10.2c), but these are typically difficult to find, are not present in all cases, and are not necessary for the diagnosis. Islands of hyaline or cellular, but benign, cartilage are a common feature being found in approximately 50% of these neoplasms (Fig.10.2d), a much higher incidence than in embryonal rhabdomyosarcoma arising at other sites [3–9]. In occasional cases, there are foci resembling alveolar rhabdomyosarcoma, or collections of pleomorphic cells with multilobated nuclei are present; the clinical significance of these features is uncertain. Hyaline globules may be present in association with the pleomorphic cells. There are commonly areas of hemorrhage with extravasated erythrocytes or necrosis. The hemorrhage may be so extensive as to mask the underlying hypercellular areas to some extent.

Positive nuclear staining with the skeletal muscle markers myogenin and myoD1 assists in diagnosis, but typically only a minor proportion of the nuclei are immunoreactive (Fig. 10.3). Desmin is usually positive but normal cervical stroma is also desmin positive. Hormone receptors (estrogen receptor (ER) and progesterone receptor (PR)) are generally negative, as is smooth muscle actin and h-caldesmon.

Given the polypoid nature of the lesion and the presence of a cambium layer, often the main differential diagnosis is an adenosarcoma with heterologous stromal elements, especially in those cases where glands are present deep within the core of the neoplasm. An absence of the typical phyllodes-like (club-like or leaflike) architecture of adenosarcoma is helpful, as is the usual relative paucity of glands deep within the stroma. Adenosarcomas usually occur in an older age group. However, in some cases the distinction between cervical embryonal rhabdomyosarcoma and adenosarcoma may be arbitrary. Given the hypocellular background, an unusual benign endocervical or endometrial polyp or endometriosis may also be considered in the differential diagnosis, but these are usually easily excluded given the morphological features described above. Carcinosarcoma is excluded due to the absence of a malignant epithelial component.

Most cervical embryonal rhabdomyosarcomas are treated by a combination of surgery (which may be radical or comprise local conservative excision) and chemotherapy, and the overall prognosis is good with an approximately 80% overall survival [14]. However, there are few large series with significant follow-up. In agreement with these findings, patients with cervical embryonal rhabdomyosarcoma presented at lower stage and had a better 5-year prognosis than younger patients with vaginal rhabdomyosarcoma in a review of the SEER database [14]. The main adverse prognostic feature is deep invasion of the cervical stroma, but this is uncommon.

Myofibroblastoma of the lower female genital tract was first described by Laskin et al. and was originally referred to as superficial cervicovaginal myofibroblastoma [15]. These authors reported a distinctive mesenchymal tumor arising in the superficial lamina propria of the cervix and vagina [15]. The term superficial cervicovaginal myofibroblastoma was proposed to encompass the superficial location in the cervix or vagina and presumed myofibroblastic differentiation. A subsequent series of cases involved the vagina and the vulva, and the term superficial myofibroblastoma of the lower female genital tract was proposed since some neoplasms have a vulval location [16, 17].

These neoplasms occur in premenopausal or postmenopausal women and usually present as polypoid lesions. Some patients have been on tamoxifen, raising the possibility of an association with this medication [15–17]. Based on the morphology and follow-up, superficial myofibroblastoma of the lower female genital tract is a benign lesion, although there is uncommonly local recurrence following excision [15–17]. Metastasis or malignant transformation has not been reported.

Grossly these are well circumscribed and are often, but not always, polypoid in appearance. Histological examination shows a well-circumscribed but unencapsulated lesion covered by unremarkable squamous or glandular epithelium. Deep to the surface epithelium, there is usually an uninvolved grenz zone, although sometimes the lesion extends up to the epithelial-stromal junction. There are typically areas of varying cellularity, the constituent cells having bland ovoid, spindled, or stellate nuclei, sometimes with a somewhat wavy appearance. The cells are embedded in a finely collagenous stroma, sometimes with thicker collagen bundles (Fig. 10.4a). Multiple architectural patterns, including lacelike, sievelike, and fascicular, which result in a heterogeneous appearance, are a characteristic feature. The stroma is often overtly edematous which results in the lacelike architecture. Occasionally, there is stromal myxoid change. Few or no mitoses are present.

The cells are positive with vimentin and almost always with desmin [15–17]. CD34 and smooth muscle actin (SMA) are positive in some cases, and most are ER and PR positive. S100, EMA, h-caldesmon, HMGA2, and cytokeratins are negative. Desmin staining typically highlights the ramifying dendritic processes of many of the tumor cells (Fig. 10.4b) [15–17]. The immunophenotype is nonspecific and identical to that of many of the other site-specific mesenchymal lesions which involve the lower female genital tract, especially the vulva and vagina.

The main differential diagnosis in the cervix is likely to be an unusual endocervical polyp, and focally the stroma of endocervical polyps may resemble myofibroblastoma of the lower female genital tract. However, mucinous glands are usually present throughout endocervical polyps, while more than an occasional entrapped gland is unusual in myofibroblastoma of the lower female genital tract. A fibroepithelial polyp may also enter into the differential diagnosis. The grenz zone which is typical of superficial myofibroblastoma of the lower female genital tract is not a feature of fibroepithelial polyp, and the former is characterized by a more heterogeneous appearance with a variety of architectural patterns. Negative staining with S100 helps to exclude a neural lesion which may enter into the differential diagnosis since some of the morphological features, such as the presence of wavy nuclei, may raise this possibility.

Many other mesenchymal tumors have been reported as primary neoplasms in the cervix, but these are generally more common in the corpus. They include endometrial stromal neoplasms, uterine tumor resembling ovarian sex cord tumor (UTROSCT), alveolar soft part sarcoma (more common in the cervix than uterine corpus), inflammatory myofibroblastic tumor, epithelioid sarcoma, perivascular epithelioid cell tumor (PEComa), malignant rhabdoid tumor, schwannoma, neurofibroma, hemangioma, rhabdomyoma, liposarcoma, angiosarcoma, tumors in the Ewing family, and malignant peripheral nerve sheath tumor (malignant schwannoma) ([18–25]; reviewed in [25]). The morphological and immunohistochemical features are identical to when these neoplasms occur at more usual sites, but the pathologist may not think of the diagnosis given the rarity of these neoplasms in the cervix. Three cases of an S100- and CD34-positive cervical sarcoma which the authors termed fibroblastic malignant peripheral nerve sheath tumor (neurofibrosarcoma) have been reported [26]. Rare cases of pseudoneoplastic myxoid change of the cervical stroma have been reported (Fig. 10.5) [27, 28]. Fibroepithelial polyps, similar to those occurring in the vulva or vagina, rarely arise within the cervix and may contain a population of atypical stromal fibroblasts.

The same variety of mixed epithelial and mesenchymal neoplasms (mixed Mullerian tumors) that affect the uterine corpus, namely, carcinosarcoma, adenofibroma, and adenosarcoma, occurs more uncommonly in the cervix [29]. There is also a specific type of adenomyoma, termed an endocervical adenomyoma, which occurs within the cervix.