Diagnostic efficacy of ultrasound in the detection of inguinofemoral metastases

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Review

HJOG 2025, 24 (2), 138-142| doi: 10.33574/hjog.0593

Vasilios Pergialiotis1, Sofoklis Stavros2, Ioannis Rodolakis1, Anastasios Potiris2, Periklis Papanagopoulos2, Georgios Daskalakis2, Aikaterini Domali1

1First Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, “Alexandra” General Hospital, National and Kapodistrian University of Athens, Athens, Greece
2Third Department of Obstetrics and Gynecology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece

Correspondence: Vasilios Pergialiotis, MD, MSc, PhD, 6 Danaidon str., Halandri 15232 – Greece, e-mail: pergialiotis@yahoo.com

Abstract

Ultrasonographic assessment of inguinofemoral lymph nodes has been proposed as an alternative to standard imaging techniques since the 2000s. Since then, several researchers indicated its high diagnostic accuracy, denoting that its limitations seem to be comparable to those of magnetic resonance imaging and potentially of positron emission computerized tomography. Although strict consensus about its application in current clinical practice is still lacking, established morphological criteria have already been proposed and are associated with excellent sensitivity and specificity. Considering the cost effectiveness of the method compared to traditional imaging it becomes evident that in the future it may represent the standard of care not only for the preoperative assessment of patients at risk, but also during the postoperative period in order to help the early detection of lymph node metastases which may significantly alter the survival outcomes of these patients.

Keywords: Vulvar cancer, lymph node, groin, inguinofemoral.

Introduction­

Vulvar cancer is relatively rare, accounting for approximately 3–5% of all female genital tract malignancies. It is the fourth most common gynecologic malignancy after uterine, ovarian, and cervical cancer and represents 5% of all cancer cases in females with its annual incidence ranging between 1.2–1.3 per 100,000 women (1). Although the incidence appears to be increasing, the death rate continues to decrease, and the current five-year survival rate is 68–76% depending of the tumor stage (2, 3). The age of onset of the disease is today 15 years older than that reported thirty years ago, with a median of 70 years (3). The reasons for the increasing incidence of vulvar cancer in elderly women may include increasing life expectancy, the long-term use of postmenopausal hormone replacement therapy, the increasing numbers of altered immunosuppressed patients, premalignant disease, and chronic inflammation seen in young women, as well as the increasing numbers of women affected by infection with a prolonged lifespan of the virus and the increased numbers of sexually active elderly women (4).

Squamous histology is the predominant form (90%), with the more frequent histologic subtypes being keratinizing squamous cell carcinoma, which accounts for 50% or more of cases; basaloid/warty, which is less (evident) 20%, and most usually seen in younger women; and intermediate tumors that account for only 10% of cases (1).

The presence of metastases in inguinal lymph nodes is a major prognostic factor, with a 35% risk of involvement starting from a 1-mm depth of invasion (5). Factors influencing lymph node metastasis include tumor size, perineural invasion (PNI), and lymphovascular space invasion (LVSI). Machine learning models, such as the RandomForest algorithm, have shown promise in predicting lymph node involvement, achieving an AUC of 0.820 (6). These advancements highlight the importance of accurate lymph node evaluation in vulvar cancer management, leading to better surgical outcomes and survival rates.

Modern ultrasound can become an invaluable tool for the assessment of inguinofemoral vulvar metastases, as emerging scientific evidence denotes its superior diagnostic efficacy, underlining its importance as an office tool for the assessment of patients in an office setting. To date, however, it is not included in clinical staging algorithms. In the present review we summarize the available evidence.

Current evidence

Magnetic resonance imaging MRI represents the standard of care for preoperative staging of patients with vulvar cancer as it accurately denotes the presence of locally extended disease as well as the presence of regional and distant lymphatic and/or hematogenous metastases (7, 8). However, newer studies support that in specialized centers, proper staging of the inguinofemoral region may be feasible with the use of ultrasound as well.

Ultrasound in combination with fine needle aspiration cytology (FNAC)

The first reliable evidence in this field was provided in 2003 by Hall et al that reviewed a series of 44 patients and observed that the combination of ultrasound with ultrasound guided cytology (FNAC) was extremely accurate as it confirmed the final histologic diagnosis in 92% of cases, denoting its importance in the field of vulvar cancer (9). In 2019, a research team from Italy evaluated the diagnostic accuracy of FNAC and observed that it was accompanied by a sensitivity that reached 77% and a specificity of 100% (10). Moreover, they denoted that cases that were not detected by the ultrasound had a millimetric inguinofemoral disease that ranged between 0.1 to 0.6 cm which may be undetectable by current imaging techniques such as MRI scan and positron emission computerized tomography (PET-CT) (11). Similar results were obtained from smaller studies as well indicating the reproducibility of the method and a steady specificity which ranges between adequate and optimal levels (69% to 91% of cases) (12, 13). It should be noted in this point that a controlled study, published in 2006, that compared the diagnostic accuracy of ultrasound and ultrasound guided FNAC with preoperative CT indicated a clear superiority of the former method as it was associated with a calculated sensitivity, specificity, negative predictive value, and positive predictive value of 80%, 100%, 93%, and 100% compared to 58%, 75%, 75%, and 58% for CT alone (14).

Ultrasound alone for the assessment of groin lymph nodes

Earlier studies have demonstrated that ultrasonography exhibits high diagnostic accuracy in detecting suspicious inguinofemoral lymph nodes. In a series of 60 patients, de Gregorio et al observed that the method correctly identified the presence (or absence) of lymph node metastases in 92/107 surgical retrieved lymph nodes, resulting in a sensitivity of 76.3%, a specificity of 91.3%, and positive and negative predictive values that were 82.9% and 87.5%, respectively (15).

Standardized methods for the assessment of groin lymph nodes metastases are not available yet, compared to other established taxonomy systems in endometrial and ovarian cancer (16, 17). However, an effort to reach specific criteria has been already published with a proposed protocol that aims to homogenize reporting of the lymph nodes location and status (18). These criteria  are based on a large single center study (MorphoNode study), that included 144 patients and indicated that establishing specific criteria may be feasible as it may provide specific sensitivity and specificity rates for the variables that are assessed (19). Specifically, in this study, researchers classified the lymph nodes in five distinct categories, namely normal; reactive-but-negative; minimally suspicious/probably negative; moderately suspicious; and highly suspicious/positive according to the subjective management of morphological criteria that included the presence of a globular shape, the loss of homogenous echostructure, the presence of intranodal deposits or hilar anomalies, evidence of cortical node thinning and/or node grouping. These were combined with dimensional parameters that included evaluation of the small and large axis of the lymph nodes, evaluation of the long/short axis ratio using a cut-off value of <2 as suspicious, evaluation of the cortical and medullary thickness of the predominant lymph node along with calculation of the cortical/medullary thickness ratio considering a value >1 as suspicious. Of all these variables researchers indicated that cortical axis, short axis, cortical/medullary ratio and binomial final overall assessment were associated with the highest sensitivity and specificity for detecting suspicious lymph nodes which were afterwards subjected to FNAC that was ultimately compared to standard excisional biopsy.

Based on this study, and the criteria that were set, researchers performed external validation of the study`s findings opting to proceed by developing a model evaluates morphological ultrasonographic data (20). In three years, they managed to recruit 237 cases of whom 127 had sufficient data to be included in the study. A total of 237 lymph nodes were evaluated of which 162 were negative for disease and 75 metastatic. Through this study, the authors managed to obtain four specific morphologic signatures with a point risk of 100%, 81%, 16% and 4% to indicate lymph node metastases.

Extending the barriers of ultrasonographic evaluation, a research team from Brisbane Australia indicated that in selected patients, surgical evaluation of groin lymphatics can be omitted and be replaced by serial ultrasound with high rates of diagnostic accuracy and acceptable disease associated mortality (21).

Conclusion

Ultrasonographic assessment of lymph node metastases seems to be feasible in vulvar cancer patients as the procedure may be combined with FNAC to increase its diagnostic accuracy that may surpass traditional imaging methods for preoperative assessment of regional metastases. Specific sonographic criteria have been already set, however, further validation of these data is needed prior to reaching a firm consensus that may change our practice, as the majority of published studies refers to small series of patients, therefore, precluding definitive extrapolation of the importance of their findings in other populations. In the future, ultrasound may become an invaluable method for the preoperative assessment and postoperative follow-up of patients with vulvar cancer as it represents a relatively inexpensive tool that must be performed by experienced physicians to help maintain appropriate reporting standards. 

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