A 22-Year-Old Woman With a Large Pelvic Mass (2006)

A 22-year-old, gravida 3, para 2, woman presented with lower abdominal discomfort, vaginal fullness, and difficulty inserting and removing tampons during menses of 3-months' duration. Physical examination was significant for suprapubic and right lower quadrant tenderness, but no acute peritoneal signs such as rigidity or guarding were present. Pelvic examination revealed a large firm pelvic mass apparently located in the posterior aspect of the deep vagina. Computed tomography scanning of the pelvis showed a well-circumscribed proximal vaginal tumor mass (7.8 × 6.5 × 6.3 cm) anterior to the rectum with compression of the cervix. Magnetic resonance imaging study showed a 7.6 × 6.6 cm heterogeneous enhancing pelvic mass in the proximal vagina invading the right obturatorius internus muscle with radiologic features of central necrosis (Figure 1, vaginal tumor labeled as T, cervix labeled as C). The lesion was radiologically suspicious for a malignant neoplasm arising from the right upper vaginal wall with intact uterine corpus and cervix. Transvaginal incisional biopsy of the mass (3 × 1.3 × 0.8 cm in aggregate) was obtained and routine hematoxylin-eosin and immunohistochemical stains with desmin, myogenin, smooth muscle actin, cytokeratin AE1/AE3, and epithelial membrane antigen were performed.Hematoxylin-eosin stained sections showed that the tumor was composed of large atypical polygonal or round cells in sheets with extensive necrosis and focal areas of spindling. These undifferentiated cells had abundant deeply eosinophilic cytoplasm; high mitotic activity (Figure 2, A); and moderate pleomorphism with occasional large, multinucleated, bizarre, eosinophilic anaplastic cells (Figure 2, B). No cross striations were identified. There was no primitive small blue cell component or malignant glandular element. Immunohistochemical tumor cells were diffusely positive for desmin (Figure 3) with scattered nuclear staining for myogenin (Figure 3, inset) and focal cytoplasmic staining for cytokeratin AE1/AE3 (Figure 4). However, staining for smooth muscle actin and epithelial membrane antigen were negative.What is your diagnosis?A 22-year-old, gravida 3, para 2, woman presented with a large pelvic mass. Computed tomography and magnetic resonance imaging studies localized the mass to the right upper vaginal wall with intact uterine corpus and cervix. The biopsy of the tumor mass was composed of large atypical polygonal or round cells in sheets with extensive necrosis. The undifferentiated cells had abundant deeply eosinophilic cytoplasm; high mitotic activity; and moderate pleomorphism with occasional large, multinucleated, bizarre, eosinophilic anaplastic cells identified. There was no primitive small blue cell component or malignant glandular element. Tumor cells were diffusely positive for desmin with scattered nuclear staining for myogenin and focal strong cytoplasmic staining for cytokeratin AE1/AE3 and were negative for smooth muscle actin and epithelial membrane antigen. The morphologic and immunophenotypic pattern supports the diagnosis of pleomorphic sarcomatoid neoplasm with rhabdomyoblastic and epithelial differentiation. Differential diagnoses including vaginal pleomorphic rhabdomyosarcoma (RMS), anaplastic embryonal RMS, mixed malignant müllerian tumor, and glassy cell carcinoma of uterine cervix are discussed.The morphologic and immunohistochemical features of the pelvic tumor indicate a pleomorphic sarcomatoid neoplasm with rhabdomyoblastic and epithelial differentiation. Although a variety of sarcomas may have heterologous rhabdomyoblastic differentiation, presence of relatively well-differentiated or typical component of the original tumor is necessary for their identification. The tumor in this patient is pleomorphic and epithelioid and contains no such characteristically differentiated areas. Differential diagnosis includes pleomorphic RMS, anaplastic embryonal RMS (also called embryonal RMS with diffuse anaplasia), and malignant mixed müllerian tumor (MMMT). The young age of the patient also placed cervical glassy cell carcinoma in the differential diagnosis. Inherent sampling limitation of the biopsy material should be recognized. It cannot always be used to sort out entities with dominant similar features and only minor or focal differences. Thorough histologic evaluation of the whole lesion is usually needed for definite classification. The patient received standard chemotherapy (vincristine, actinomycin D, and cyclophosphamide) and radiation therapy. Eight months after initial diagnosis, computed tomography scan confirmed multiple pulmonary nodules up to 1.5 cm in diameter bilaterally and 2 small nodules in the right lobe of the liver, consistent with distant metastasis. The patient died 1 year after the initial diagnosis. No surgical resection or postmortem examination was available for further pathologic evaluation.RMS is a malignant neoplasm of primitive mesenchymal cell origin, characterized by morphologic, immunohistochemical, or ultrastructural evidence of striated muscle or sarcomeric differentiation. It may arise in almost any soft tissue site in the body even at sites that usually do not contain skeletal muscle. The most common primary sites are genitourinary (24%), parameningeal (16%), extremity (19%), orbit (9%), head and neck (10%), and miscellaneous other sites (22%).1 Presentation of RMS is often site-dependent, with an enlarging mass compressing or invading nearby structures. All 3 major variants (embryonal, alveolar, and pleomorphic) are extremely rare and show distinct histologic appearances. The embryonal and alveolar subsets occur mainly in children and teenagers and are the most common soft tissue sarcomas in that age group. Pleomorphic RMS accounts for less than 5% of RMS cases and occurs more commonly in the adult population and carries a relatively poor prognosis. Because histopathologic classification bears prognostic significance,2 accurate diagnosis is important for appropriate treatment assignment and analysis of outcome data.Pleomorphic RMS usually occurs in the deep soft tissue of the lower extremity and trunk in adults older than 45 years. Pleomorphic RMS of the vagina is very rare and was recently reported in a postmenopausal woman.3 Immunohistochemical study supports its diagnosis and also distinguishes it from liposarcoma or malignant fibrous histiocytoma. Large pleomorphic polygonal “rhabdoid cells” with brightly eosinophilic cytoplasm and multinucleated tumor giant cells are characteristic. At least 1 skeletal muscle-specific marker by immunohistochemistry is required for the diagnosis. Desmin is usually diffusely positive in RMS, but it does not differentiate RMS from leiomyosarcoma. Smooth muscle actin (a marker of smooth muscle differentiation) is negative in RMS, whereas myogenin (a gene product that induces skeletal muscle differentiation) is focally positive with nuclear staining. Electron microscopy could also be of value in identifying the cytoplasmic myosin-ribosome complex of skeletal muscle, characterized by short parallel bundles of myosin filaments and attached ribosome in a single file arrangement. In this case, tumor cells are diffusely positive for desmin and have scattered nuclear staining for myogenin and focal positivity for cytokeratin (AE1/AE3). Although embryonal RMS can aberrantly express cytokeratin, pleomorphic RMS is often negative for cytokeratin expression in the previously published literature.Embryonal RMS is essentially a small blue cell tumor and usually occurs in children and adolescents. It also contains dense groups of rhabdomyoblasts with small nuclei and loose myxoid stroma. Rhabdomyoblasts can take on several characteristic morphologic appearances including spindle cells, strap cells, spider cells, and racquet-shaped cells. Cross striations in tumor cells characteristic of skeletal muscle or plump rhabdomyoblasts are occasionally noted. However, immunohistochemical staining (eg, myogenin, MyoD, myoglobin, and desmin) is helpful for definitive diagnosis. The presence of enlarged atypical cells with hyperchromatic nuclei defines the anaplastic subtype of embryonal RMS, as recently reported in the uterine cervix.4 Although pleomorphic cells are readily seen in this case and focal cytokeratin positivity has been reported in embryonal RMS, small blue cells (blastemic or embryonal component) made the diagnosis of anaplastic embryonal RMS (embryonal RMS with diffuse anaplasia) less likely.As the proximal portion of the vagina is derived from the müllerian duct, a high-grade sarcoma with epithelioid differentiation also placed MMMT with heterologous element of the female genital tract into the differential diagnosis. MMMT is a highly aggressive neoplasm usually seen in elderly women. It is characterized by a biphasic pattern of malignant epithelial glandular and stromal spindle cells with some spindle cells positive for cytokeratin. Recent studies indicate that MMMT is biphasic in appearance but monoclonal at the molecular level (the combination theory of histogenesis).5 MMMT of vaginal origin is rare, and there are only a few reported cases in the literature.6 Although the focal cytokeratin reactivity and striking rhabdomyoblastic differentiation in the case could be considered as epithelial differentiation and heterologous element in MMMT, the diagnosis of MMMT cannot be confirmed because of the lack of histologic epithelial element identified in the specimen. In addition, similar to pleomorphic RMS, the young age of the patient is unusual for the diagnosis of MMMT.Cervical glassy cell carcinoma is initially considered, as it is a high-grade tumor usually seen in young females (mean age, 30–35 years). This distinct type of poorly differentiated adenosquamous carcinoma is a rare variant of cervical cancer with aggressive clinical behavior and sometimes associated with pregnancy.7 It is characterized radiologically by an enlarged barrel-shaped cervix and microscopically by solid nests of tumor cells containing pale to eosinophilic finely granular ground glass-type cytoplasm (hence the name of glassy cell carcinoma), distinct cell membrane border, large eosinophilic nuclei, and prominent nucleoli with frequent mitotic figures. The tumor cells are commonly surrounded by heavy inflammatory infiltrate containing eosinophils and plasma cells in the fibrous stroma and polymorphonuclear neutrophils among tumor cells. However, unlike pleomorphic RMS, cervical glassy cell carcinoma does not show significant pleomorphism with bizarre and highly atypical cells, and desmin and myogenin reactivity has never been reported in glassy cell carcinoma; therefore, it can be ruled out.In summary, the overall morphology and immunophenotype of the tumor in the biopsy material support the diagnosis of pleomorphic sarcomatoid neoplasm with rhabdomyoblastic and epithelioid differentiation and main differential considerations are pleomorphic RMS, anaplastic embryonal RMS, and MMMT. The lack of availability of the excisional specimen for evaluation precludes further classification of the tumor.