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The role of imaging in recurrent vulvar carcinoma
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A 57-year-old black woman with prior history of hysterectomy presented with vaginal pain and discomfort in early 2012.
Her physical exam was notable for a large irregular mass arising from the right labia majora that extended to the left labia majora, measuring approximately 4 cm x 2 cm.
The patient underwent radical vulvectomy along with vaginoplasty and reconstruction. The pathology showed an invasive poorly differentiated squamous cell keratinizing carcinoma in the right vulva, with the greatest dimension measuring 1.2 cm wide x 4 cm deep. Additionally, there were two smaller foci of invasive carcinoma.
All three foci were arising in a background of extensive carcinoma in situ/high-grade squamous intraepithelial lesion. The neoplasm was excised entirely with negative surgical margins, with the closest margin measuring 0.5 cm. Her final pathologic staging was IA (T1a, Nx, Mx).
Imaging results
Three months later, she returned with recurrent vaginal discomfort and underwent a PET/CT to evaluate for lymph node metastasis. Although there was no definite anatomic imaging to correlate for a primary vulvar malignancy, there was a discrete focus of abnormal metabolic activity corresponding to the anterior left vulvar fold with a maximum standard uptake value (SUV) of 4.9 (Figure 1).
Figure 1a. A PET/CT scan on Jan. 7, 2013, demonstrated a discrete focus of abnormal metabolic activity with a maximum standard uptake value (SUV) of 4.9, corresponding to amorphous soft tissue inseparable from the normal vulvar folds. This focus appears slightly left of midline, suggesting a left-sided primary malignancy. No abnormal metabolic activity extending toward the vaginal vault was observed.
Figure 1b. There is a right inguinal lymph node measuring 1 cm x 0.8 cm, associated with faint but focal metabolic activity, with a maximum SUV of 1.3.
There also was a subcentimeter right inguinal lymph node with low-grade metabolic activity (Figure 2). At that point, she was offered resection with lymph node dissection; however, she declined and was lost to follow-up.
She returned several months later, presenting with a large right vulvar mass that extended toward the urethra. A biopsy confirmed the suspicion of an invasive vulvar squamous cell carcinoma, and a Pap smear showed cervical high-grade squamous intraepithelial lesion with high-risk HPV.
A new PET/CT exam, performed 10 months after the initial one, showed a new focus of metabolic activity in the middle of the vaginal vault to the right of the urethra, along with the known right-sided vulvar cancer. In addition, the right inguinal lymph node — which previously had an SUV of 1.3 — now measured 2.1 cm with an SUV of 5.7 (Figures 2a-2c).
Figure 2a. A PET/CT scan on Oct. 14, 2013, taken in the same location of the previously seen focal hypermetabolism, shows a discrete focus of metabolic activity that corresponds to the expected location of the distal female urethra. The configuration of metabolic activity is lobular and nonspecific, especially given the small bubble of air seen at this level.
Figure 2b. The PET/CT scan shows a new focus of metabolic activity adjacent to a bubble of air at the level of the mid- to superior vaginal vault. It is to the right of midline and not at the expected level of the female urethra.
Figure 2c. The previously seen hypermetabolic right inguinal lymph node has increased in size and associated metabolic activity, now measuring 2.1 cm in size with a maximum SUV of 5.7. It previously measured 1 cm x 0.8 cm with a maximum SUV of 1.3. The other remaining lymph nodes in the right inguinal station, as well as the rest of the pelvis, are unchanged. No evidence of newly suspicious nodes in the abdomen are observed.
It was unclear if these new findings on PET/CT were due to inflammatory/physiologic uptake or new malignant foci. A contrast-enhanced MRI, performed to provide better anatomic evaluation, showed a soft tissue mass surrounding the distal female urethra, which appeared contiguous with enhancement along the medial labial fold (Figure 3). Asymmetric nodular expansion of the mid-vaginal vault on the right also was observed with no enhancement. A round, enlarged right inguinal node also was noted, as seen on PET/CT.
Figure 3. A T1 hypointense T2 hypointense enhancing soft tissue mass located around and mostly posterior to the distal female urethra measuring 2.8 cm x 2 cm x 2.6 cm is visualized, corresponding to an area of increased metabolic activity seen on PET/CT. This finding appears to be contiguous, with enhancement along the labial folds medially. A round inguinal lymph node measuring 2.2 cm also is seen, increased in size compared with the PET/CT performed in January 2013.
Source: Images courtesy of M. Ghesani, MD, reprinted with permission.
Incidence and symptoms
Vulvar cancer accounts for 4% of gynecologic cancers, with about 5,000 new cases each year in the United States. It is a disease of the elderly, with most cases presenting in women older than 60 years.
Most vulvar cancers are squamous cell carcinomas that arise from the labia majora of the vulva. Of note, the vulva comprises the labia majora, labia minora, clitoris, vestibule and urethral meatus.
Vulvar carcinomas can be associated with HPV infection, a known etiologic factor of cervical cancer. In these cases, it usually arises in the setting of vulvar intraepithelial lesion and is associated with earlier age of diagnosis, as well as a more aggressive behavior.
On the contrary, non–HPV-related vulvar cancer usually is associated with lichen sclerosis seen in elderly women. Other malignancies that can arise in the vulvar area include melanoma, basal cell carcinoma, sarcoma and Paget’s disease of the vulva, which is frequently associated with adenocarcinomas.
Pain, dyspareunia, pruritus, bleeding and irritation are the most common presenting symptoms, and a vulvar mass frequently is found on physical exam. The most important prognostic factors of vulvar cancer are the depth of invasion, size of the lesion, presence of lymphovascular invasion, number of involved lymph nodes and presence of extracapsular extension. These factors are reflected in the most current staging systems used for vulvar cancer, which are the 7th edition of the American Joint Committee on Cancer (AJCC) and the International Federation of Gynecology and Obstetrics (FIGO) staging systems.
Role of imaging
A combination of clinical and pathological information is used to accurately stage vaginal cancer. This is because clinical staging alone can miss up to 30% of positive inguinofemoral lymph nodes. Tailored surgery and neoadjuvant chemoradiation therapy are taking precedence over traditional radical vulvectomy and bilateral inguinofemoral lymphadenectomy, thereby increasing the demand for accurate pretreatment assessment using MRI and PET/CT. Surgical lymph node dissection also has been associated with significant morbidity, and radical vulvectomy often is performed with distal urethrectomy, leading to urinary incontinence and urinary tract infections.
To best evaluate vulvar anatomy and soft tissues, MRI is the most accurate. The tumor is best seen on T2-weighted sequences as intermediate to signal intensity mass or thickening of the vulva. Contrast-enhanced fat-suppressed T1-weighted images can show tumor extent. Regional metastatic lymph nodes may appear to have a ratio of short- to long-axis diameter of 0.75 or greater, irregular contours, cystic change or necrosis or loss of fatty hilum, or they may demonstrate similar signal intensity characteristics as the tumor.
When comparing studies that have evaluated the sensitivity and specificity of MRI, FDG-PET, CT and ultrasound-guided fine needle aspiration biopsy for the evaluation of nodal metastasis, ultrasound-guided fine needle aspiration biopsy has been shown to be the most reliable method, with specificity ranging from 82% to 100% and sensitivity ranging from 80% to 93%. FDG-PET had high specificity (95%) and lower sensitivity (67%).
MRI sensitivity has ranged from 50% to 89%, with a specificity of 89% to 100%. However, with MRI, stage I cancer often is too small to be detected, and tumors that present “en plaque” — which are extensive in size — also may be difficult to evaluate. Imaging procedures such as MRI are used to assess for depth of tumor invasion, local extension — such as to the urethral meatus, vagina, perineal muscles or anal canal — and lymphatic and hematogenous spread. For distant metastases, CT of the abdomen and pelvis is used for tumors larger than 2 cm, or those that fall into category T2 or above. It is unclear if routine use of CT or PET/CT is indicated for surveillance.
Treatment
Early-stage vulvar cancer, defined as stages I and II, usually is treated with radical local excision, with the addition of ipsilateral or bilateral inguinofemoral lymphadenectomy depending on the size and the location of the tumor. The current role of sentinel lymph node mapping is being studied to select the most appropriate candidates for inguinofemoral lymphadenectomy.
Locally advanced disease, defined as stage III or IVA — meaning cancer that has spread to the regional lymph nodes or has extended to the proximal 2/3 of the urethra or the vagina, or the surrounding organs (eg, bladder, rectum, pelvic bone) — ideally should be treated with surgical excision. Adjuvant radiation or chemoradiation can be used after surgical excision in cases of positive surgical margins, lymphovascular invasion and, most importantly, positive lymph nodes where it has been shown to increase OS.
In cases in which surgical excision is not possible (eg, involvement of vital structures or the patient is not a surgical candidate), primary radiation or combined chemotherapy with radiation can be used. Primary chemoradiation sometimes can shrink tumors enough and convert an unresectable tumor to resectable in patients who are surgical candidates.
The optimal chemotherapy combined with radiation is not clearly defined. Several agents — including 5-FU, mitomycin or cisplatin — have been used. Most authors would recommend single-agent cisplatin. This is based on extrapolation from the cervical cancer literature, where single-agent cisplatin was equally effective to — and less toxic than — the combination of 5-FU and cisplatin.
Vulvar cancer can relapse after therapy, either locally, regionally (lymph nodes) or distally. Selection of treatment in the relapsed setting is based on the location and the prior therapies. For isolated local and regional recurrences, re-excision would be the therapy of choice. Chemoradiation can be used in nonsurgical candidates. Distal relapses are managed as metastatic disease.
For our patient who had undergone radical vulvectomy at her initial presentation, wide local excision with inguinofemoral lymphadenectomy and adjuvant therapy, as was initially offered to her, would be the most appropriate treatment. Unfortunately, our patient declined surgical intervention.
Management of metastatic disease is not clearly defined, and the lungs are the most frequent site of metastasis. Most clinicians would use either single-agent chemotherapy or combination chemotherapy. Although there are not prospective phase 3 trials, most oncologists use platinum-based regimens, extrapolating from the cervical and head and neck literature.
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For more information:
Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center, an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons, and a HemOnc Today Editorial Board member. He can be reached at Department of Radiology, Beth Israel Medical Center, First Avenue at 16th Street, New York, NY 10003; email: mghesani@chpnet.org.
Bo Li, MD, is a radiology resident at St. Luke’s Roosevelt Hospital Center.
Grigorios Chrysofakis, MD, is a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital Center.