Imaging Features of Uncommon Gynecologic Cancers.

Cancer of the uterine cervix is the third most common gynecologic malignancy and the third leading cause of death among gynecologic cancers in the United States [ 1 ]. The most common histologic type of cervical carcinoma is squamous cell carcinoma (90%) followed by adenocarcinoma (5–10%). Adenoma malignum (also known as minimal deviation adenocarcinoma) is a subtype of mucinous adenocarcinoma of the cervix. Its prevalence is about 3% of all cervical adenocarcinomas. Neuroendocrine cancers are rare and highly aggressive cervical malignancies. They are classified as typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. Other rare histologic types include melanoma and, among nonepithelial types, lymphoma and sarcoma. Patients may present with abnormal vaginal discharge and bleeding. Definitive diagnosis requires biopsy during physical examination or histopathologic analysis. Imaging plays a fundamental role in the evaluation of extent of disease. MRI is the modality of choice for evaluating the extent of disease; CT and PET/CT are viable for the evaluation of nodal and distant metastasis. FIGO staging is the most widely used staging system for cervical carcinoma, regardless of histologic subtype [ 30 ] ( Table 4 ). The MRI findings for rare cervical cancers are summarized in Table 5 . Adenoma malignum is often associated with Peutz-Jeghers syndrome, which is characterized by mucocutaneous pigmentation, multiple hamartomatous polyps of the intestinal tract, and ovarian mucinous tumors. The most common initial symptom is a watery vaginal discharge. The tumor is composed of well-differentiated endocervical glands filled with mucin, which invade the deeper portion of the cervical stroma. The role of the radiologist is differentiating adenoma malignum from a broad spectrum of multicystic benign lesions in the uterine cervix, including deep nabothian cysts and florid endocervical hyperplasia. On ultrasound, adenoma malignum may appear as a hyperechoic multilocular endocervical mass with cystic components. On MRI, adenoma malignum is seen as a multicystic mass showing slightly high signal intensity on T1-weighted images and markedly high signal intensity on T2-weighted images, with some internal enhancing solid components that extend into the cervical stroma. The locules of the multicystic lesions have smooth margins and diameters of less than 1 cm [ 31 ]. The presence of internal enhancing solid nodules is more likely to be associated with local invasion (i.e., endometrial cavity, parametria, and vagina) and nodal metastases ( Fig. 4 ). Adenoma malignum may disseminate into the peritoneal cavity even in the early stage of the disease [ 32 ]. The differential diagnosis includes deep nabothian cysts, tunnel cluster, and endocervical glandular hyperplasia. The role of CT for local staging is limited. It is used in the assessment of distant disease. PET/CT may be useful in identifying the primary site of disease in patients with adenoma malignum; however, its utility in detecting metastatic disease remains undetermined. Neuroendocrine tumors of the uterine cervix tend to show aggressive growth [ 33 ]. Although imaging cannot reliably differentiate neuroendocrine carcinoma from other types of epithelial cervical carcinomas, on MRI, neuroendocrine tumors tend to be large lobulated masses and tend to show slightly homogeneous high signal intensity on T2-weighted images and intense enhancement on dynamic multiphase T1-weighted images [ 34 ]. Small cell carcinoma is frequently accompanied by lymphadenopathy and bilateral parametrial invasion [ 34 ] ( Fig. 5 ). Melanoma rarely involves the uterine cervix. It usually occurs in the vaginal mucosa. Because of the presence of melanocytes, melanoma is typically hyperintense on T1-weighted MR images. However, melanoma may have different signal intensity characteristics according to the melanin concentration and the presence of hemorrhage [ 32 ]. Patients with cervical sarcomas tend to be younger and to have more-advanced disease at diagnosis than do patients with squamous cell carcinoma. Carcinosarcomas are the most common histologic subtype followed by leiomyosarcomas and adenosarcomas [ 35 ]. The prognosis is poor. No specific imaging diagnostic features have been described for cervical sarcoma. However, a lesion with diffusely infiltrating growth through the cervical stroma could be suggestive of the diagnosis. Malignant lymphoma frequently infiltrates the uterus in advanced disease. However, it rarely involves the uterine cervix. On MRI, the tumor tends to be hypointense on T1-weighted images and relatively hyperintense on T2-weighted images and to extensively infiltrate the cervical stroma [ 28 ]. The presence of preserved cervical epithelium may suggest the diagnosis of malignant lymphoma [ 28 ].

Vulvar carcinoma is rare, accounting for 5% of female genital tract cancers, with peak incidence occurring in the 65- to 75-year age group. Squamous cell carcinoma accounts for more than 85% of cases. Other histologic types include melanoma, mesenchymal tumors, adenocarcinoma, extramammary Paget disease, basal cell carcinoma, and Bartholin gland cancer. Risk factors for squamous cell carcinoma include older age, lichen sclerosus, human papillomavirus infection, and vulvar intraepithelial neoplasia, especially in young women. Vulvar cancer is diagnosed clinically [ 4 ]. Imaging plays a role in assessing locally advanced disease ( Table 6 ). Imaging techniques include MRI for local and pelvic nodal staging, CT or PET/CT for the assessment of distal disease, and ultrasound, which is often used for image-guided biopsy procedures. Ultrasound is useful to evaluate nodal involvement. Lymphatic supply to the vulva is rich; thus, nodal metastases occur at an early stage. Primary lymph drainage is to the femoral and inguinal nodes and then to the pelvic nodes. All vulvar cancers located within 1 cm of midline structures (i.e., clitoris, vagina, or anus) have the potential to spread bilaterally. Typical ultrasound features are increase in size (e.g., > 5 mm in short-axis diameter), rounded shape, irregular contour, and loss of the fatty hilum. Ultrasound-guided fine-needle aspiration can help with proving nodal metastatic disease [ 40 – 42 ]. On MRI, vulvar cancer appears as a solid mass with nonspecific low signal intensity on T1-weighted images and moderate-to-high signal intensity on T2-weighted images. Occasionally, it may also be difficult to discriminate whether tumors originate from the right or left labia. MRI is fundamental in determining the involvement of adjacent structures (e.g., the anal sphincter, urethra, or vaginal wall) to assist in surgical planning ( Table 6 ). Disruption of the target appearance of the urethra on T2-weighted images and interruption of the low-T2-signal vaginal wall and anal sphincter by an intermediate-T2-signal tumor are suggestive of invasion. Fat-saturated T2-weighted images, DWI, and contrast-enhanced sequences are useful for assessment of local invasion. Contrast-enhanced MRI sequences can increase staging accuracy from 75% to 85% [ 43 ]. High-resolution MRI sequences have been to achieve an accuracy of 87% in the detection and characterization of inguinal and pelvic lymph nodes [ 43 ], indicating that MRI may be useful to evaluate patients for ultrasound-guided biopsy versus sentinel lymph node detection. The primary tumor may be visualized on CT as an area of soft-tissue density in the vulva. CT provides information on the presence of pelvic lymphadenopathy and distant metastases with a sensitivity and specificity of 58% and 75%, respectively [ 40 ]. PET/CT is performed for detection of lymphadenopathy or metastatic disease. Cohn et al. [ 44 ] evaluated the role of PET/CT in detecting groin lymphadenopathy in locally advanced vulvar cancer, before nodal dissection. A 67% sensitivity, 95% specificity, 86% positive predictive value, and 86% negative predictive value were reported. Melanoma is the second most common vulvar malignancy. It shows intermediate-to-high signal intensity on T1-weighted imaging due to the paramagnetic effect of melanin, with corresponding low-to-intermediate signal intensity on T2-weighted imaging. Angiomyxoma of the vulva is a slow-growing mesenchymal tumor arising usually in premenopausal women. High signal intensity is seen on T2-weighted imaging, possibly reflecting the myxomatous stroma, and high water content may also be seen. The mass straddles the urogenital diaphragm and displaces, rather than invades, the adjacent tissues or organs [ 39 ].

The techniques used for imaging rare gynecologic cancers are identical to those used to image the more common gynecologic malignancies. A brief overview of the different modalities used is provided below. Ultrasound is the primary imaging modality used in the initial evaluation of the female pelvis. Ultrasound is performed with a trans-abdominal approach, using a 3.5–5–MHz curvilinear probe. A full bladder is necessary to provide a sonic window for ultrasound transmission from the body surface to internal organs. Transvaginal ultrasound is used for a more accurate evaluation of the endometrial cavity and ovaries. Transvaginal ultrasound is performed using a 5–8–MHz transducer. Color power and spectral Doppler techniques are used to evaluate vascularity. In the evaluation of suspected gynecologic cancers, contrast-enhanced CT of the abdomen and pelvis is performed in the portal venous phase (60–90 seconds after IV contrast medium administration at an injection rate of 2.5–3 mL/s in 70-kg patients). The use of water-density oral contrast agent is required to allow detection of small peritoneal deposits. The use of positive oral contrast agents may be useful for the recognition of small-bowel cystic peritoneal deposits, thanks to increasing contrast resolution. However, this may limit the identification of calcified peritoneal deposits. The use of ionizing radiation represents a disadvantage in young patients. Other limitations include artifacts with metallic implants and the morbidity associated with allergic reactions to iodinated contrast agents. Fasting is typically required for 4–6 hours before MRI examination to limit artifacts from bowel peristalsis. Before MRI examination, antiperistaltic agents may also be administered. Patients are asked to void before the examination, because a full bladder may cause motion artifacts. Images are acquired in the supine position using a pelvic surface-array multichannel coil. Vaginal gel opacification may be used in cases of suspected vaginal invasion. The basic imaging protocol MRI for suspected gynecologic malignancies is presented in Table 1 . Advantages of MRI include superior soft-tissue contrast, multiplanarity, and the absence of ionizing radiation. PET/CT is a functional imaging modality using a short-lived radionuclide, FDG. FDG is a glucose analog that is taken up by metabolically active cells, such as tumor cells, and subsequently is detected by PET. To provide anatomic localization of the tracer uptake, PET is combined with CT. Patients are asked to fast at least 6 hours before undergoing PET/CT. FDG is excreted by the kidneys and, therefore, the patient should empty the bladder before imaging to reduce urinary FDG obscuring tracer uptake in the rest of the pelvis. In the evaluation of suspected gynecologic cancers, false-positive findings related to physiologic radiotracer uptake may be seen in the endometrium, ovarian follicles, and corpus luteum cysts in premenopausal patients with hypercellular uterine leiomyoma and inflammatory processes within the pelvis.

Primary vaginal carcinoma is rare, accounting for only 2–3% of gynecologic malignancies; squamous cell carcinomas account for approximately 90% of vaginal malignancies. Squamous cell carcinoma is more commonly seen in postmenopausal women and tends to occur in the proximal third of the vagina, in the posterior wall. Risk factors include older age and human papillomavirus infection. Adenocarcinoma may also arise in the vagina. Vaginal cancer is most often diagnosed clinically. Imaging has no role in the diagnosis of vaginal cancer. MRI has a role in local staging and preoperative assessment of vaginal cancer. CT is often performed for the detection of pelvic lymphadenopathy or metastatic disease. Limited data are available on the utility of PET in vaginal cancer. Lamoreaux et al. [ 36 ] found that PET was superior to CT in the detection of the primary tumor and pelvic adenopathy in these patients. Clinical management depends on the size, location, and stage of tumor. On MRI, vaginal mucosa shows high signal intensity on T2-weighted images. The submucosal and muscularis layers are low signal intensity on both T1- and T2-weighted images. The surrounding external layer contains fat and a venous plexus that has slow flow, showing high signal intensity on T2-weighted images. Vaginal tumors appear isointense on T1-weighted images and as a soft-tissue mass with intermediate-to-high signal intensity on T2-weighted images [ 37 – 39 ]. Thin-section T2-weighted images in sagittal and axial planes with a small FOV are useful for detection. Tumors may also show restricted diffusion on DWI. Fat-saturated T2-weighted images and contrast-enhanced sequences are used for assessment of local invasion. Prognosis and treatment of vaginal cancer depend on the stage of the disease, as outlined by FIGO. MRI criteria that correlate to the FIGO staging system have been evaluated. In stage I disease, the tumor has invaded the epithelium but is confined to the vaginal mucosa. These lesions may be occult on MRI. The surrounding perivaginal fat is preserved. Stage II disease is defined as vaginal tumor invading the paravaginal tissues but not involving the pelvic sidewall. When tumor extends into paravaginal tissues, the high-T2-signal perivaginal fat is invaded by intermediate-T2-signal tumor ( Fig. 6 ). Stage III disease is considered when tumor extends to involve the pelvic sidewall or pelvic adenopathy. Stage IV disease is defined as tumor invading the bladder or rectum or as extrapelvic spread of disease. A mucin-producing adenocarcinoma may show higher signal components on T2-weighted images than squamous cell carcinoma, although a confident prediction of histologic subtype cannot be made on MRI alone. In advanced disease, tumor may involve pelvic floor muscles (tumor tissue visualized within 3 mm of the levator ani, obturator internus, or the piriformis muscle) and invades the bladder or rectum or both with extrapelvic spread of disease. Invasion of the bladder or rectal or both is diagnosed by identifying disruption of the normal high T2 signal of the bladder or rectal mucosa or both. Lymph node involvement is an important prognostic factor and is related to the size of the primary tumor and the depth of vaginal stromal invasion. The most commonly used MRI criteria for lymph node metastases (i.e., femoral, inguinal, and pelvic nodes) are the short-axis diameter greater than 1 cm, round shape, irregular margins, and enhancement. Vaginal melanoma can appear on T1-weighted images as a mass with higher signal intensity than the pelvic muscles, due to the paramagnetism of melanin. Vaginal sarcomas account for 2% of vaginal cancers, with rhabdomyosarcoma being the most common soft-tissue sarcoma in children and adolescents, and leiomyosarcoma the most common sarcoma in adult women. Nonspecific characteristics on imaging are seen for rhabdomyosarcoma, characterized by heterogeneous low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Heterogeneity is due to hemorrhage and necrosis within the tumor. Leiomyosarcoma on MRI appears as a bulky mixed cystic solid mass of intermediate-to-high signal intensity on T2-weighted images that shows avid contrast enhancement. Extension to the cervix, parametria, and lymph nodes can be present [ 39 ]. Primary lymphoma of the vagina is rare, accounting for 1% of primary extranodal lymphoma. Secondary lymphoma is more common. The mass is infiltrative and is of homogeneously intermediate signal intensity on T2-weighted images with homogeneous contrast enhancement. An intact mucosa is a characteristic feature of lymphoma.

In uncommon gynecologic cancers, an accurate pretreatment diagnosis based on imaging features alone may be difficult to achieve; however, imaging input in the multidisciplinary setting is crucial for optimal treatment selection. MRI may be useful to suggest the diagnosis and to evaluate the extent of disease in rare malignant neoplasms of the uterine corpus and is the most accurate technique for local staging. MRI plays a fundamental role in the evaluation of the extent of disease in cervical, vaginal, and vulvar cancer. Ultrasound represents the primary imaging modality for assessing the presence of ovarian lesions. MRI is used as a problem-solving technique and represents the modality of choice for the characterization of adnexal lesions. CT and FDG PET/CT are helpful in detection of lymphadenopathy and distant metastatic disease.

Nonepithelial ovarian cancers (accounting for 7% of primary ovarian cancers) include malignant germ cell tumors, malignant sex-cord stromal tumors, and metastases. Transvaginal ultrasound represents the primary imaging modality for assessing the presence of ovarian lesions. Sonographic indicators suggestive of malignancy include solid or cystic lesions with a maximum diameter greater than 4 cm; papillary projection (vegetation), thick wall, and thick internal septa (> 3 mm) in a cystic lesion; and irregular non-fat solid vascularized components. The presence of ascites, peritoneal implants, or hydronephrosis is also suggestive of malignancy. MRI represents a problem-solving technique and is the modality of choice for characterization of adnexal lesions ( Table 7 ). CT is the modality of choice for staging. PET/CT may play a role in preoperative staging of patients with advanced ovarian cancer and in case of suspected recurrences. Germ cell tumors are more frequent among women younger than 20 years. The most common subtypes are dysgerminoma, immature teratoma, and endodermal sinus tumor. Dysgerminoma is unilateral and predominantly solid but may contain areas of hemorrhage and necrosis. The finding of a homogeneously enhancing multilobulated mass, with prominent enhancing fibrovascular septa, has been described as a characteristic feature on MRI or CT for dysgerminoma [ 45 ]. The disease is often limited to the pelvis at presentation. If metastatic disease is present, it tends to involve lymph nodes. Immature (malignant) teratoma is usually unilateral and solid, although internal cystic areas are common. Calcification and small amounts of fat in a predominantly solid mass in a young female patient are diagnostic. The tumor capsule is not well defined, and ascites with peritoneal implants may be present. In addition, a coexistent mature teratoma may be present in the ipsilateral and in the contralateral ovary [ 45 ]. Endodermal sinus tumor or yolk sac tumor of the ovary is a malignant germ cell tumor that usually presents as a rapidly growing unilateral adnexal mass. The imaging features may range from predominantly solid to predominantly cystic; hemorrhage and hypervascular enhancement may be seen ( Fig. 7 ). The most common subtype of sex-cord stromal tumors is granulosa cell tumors. Granulosa cell tumors are characterized histologically by granulosa cells, which secrete estrogens and progesterone. Thus, granulosa cell tumors can be functional (i.e., hormonally active). They are divided into adult and juvenile types. Adult granulosa cell tumors present with menstrual disturbance or uterine bleeding in pre- or postmenopausal patients, due to estrogenic secretion and induced endometrial hyperplasia. At imaging, granulosa cell tumors are unilateral, large, encapsulated, and predominantly solid masses with cystic components [ 45 ]. The tumors may have a characteristic spongelike appearance on T2-weighted MRI [ 45 ]. Granulosa cell tumors have a particular predisposition to hemorrhage [ 45 ]. Associated endometrial thickening or mass may be seen [ 45 ]. Carcinosarcomas, also referred to as mixed müllerian tumor of the ovary, are aggressive rare tumors composed of both malignant epithelial and mesenchymal elements [ 46 ]. On conventional imaging, tumors generally are heterogeneous, large, mixed solid, and cystic adnexal masses characterized by enhancing internal septa and solid components [ 47 ]. Peritoneal implants and large amounts of ascites are usually present at diagnosis ( Fig. 8 ). Primary ovarian lymphoma is a rare manifestation of non-Hodgkin lymphoma, with diffuse large B cell lymphoma being a dominant histologic type. On MRI, ovarian lymphoma may show lower T2 signal intensity compared with most ovarian carcinomas [ 48 ]. On CT, it appears as a solid homogeneously enhancing mass, without ascites. Metastases to the ovary usually arise from primary malignancy in the stomach or colon and less frequently from the breast, lung, and pancreas. Krukenberg tumor refers to metastasis consisting of mucin signet-ring cells in a cellular stroma, arising from a carcinoma of the gastric antrum. The age at diagnosis is typically younger than that for ovarian cancer. There are no specific imaging findings. However, metastases to the ovary are typically bilateral, solid, and strongly enhancing [ 45 ]. Diffuse ovarian edema may also be present, related to the stromal infiltration by the signet-ring cells ( Fig. 9 ). Cystic and necrotic areas may be seen. CT is the primary cross-sectional imaging modality used to stage ovarian cancer. Cytoreductive surgery is the treatment of choice for patients with ovarian cancer. Optimal cytoreductive surgery (i.e., residual disease < 1 cm) is a strong predictor of survival. Accurate imaging will help to guide the surgeon to areas of disease that may be difficult to identify surgically and to describe the volume and extent of disease likely to be optimal resectable disease. Criteria for nonoptimal resectable disease have been developed. They include lymph node enlargement above the renal hilum, the presence of abdominal wall invasion, parenchymal liver metastases, and peritoneal implants of larger than 2 cm along the diaphragm, lesser sac, porta hepatis, intersegmental fissure, gallbladder fossa, gastrosplenic, gastrohepatic ligament, and root small-bowel mesentery [ 49 ]. Ascites on CT is easily identified; the presence of ascites on CT had a high positive predictive value as a sign of peritoneal metastasis.