403
PROFESSIONAL ARTICLE
The role of lymphoscintigraphy and groin sentinel node biopsy in early stage vulvar cancer
Copyright (c) 2021 Slovenian Medical Journal. This work is licensed under a
Creative Commons Attribution-NonCommercial 4.0 International License.
The role of lymphoscintigraphy and groin sentinel node 
biopsy in early stage vulvar cancer
Vloga limfoscintigrafije in biopsije varovalne bezgavke pri začetnem stadiju raka 
zunanjega spolovila
Nina Kovačević,1 Eva Drmota,2 Sebastjan Merlo1
Abstract
Vulvar cancer is a rare gynaecological malignancy which accounts to about 57 women in Slovenia every year. The most 
important prognostic factor is the presence of lymph node metastases in local or locally-advanced disease. Since only 
20–30% of women with early- stage vulvar cancer have groin metastases, inguinofemoral lymphadenectomy is an over-
treatment in 70–80% of these patients and is often associated with intra- and postoperative complications such as wound 
infection, wound dehiscence and lymphoedema of the lower extremities.
The sentinel node biopsy is a minimally invasive and safe procedure in women with early stage vulvar cancer (FIGO stage 
IB/II), where the tumour is unilateral, less than 4 cm in diameter, and without clinical/radiological evidence of lymph node 
metastases. This reduces the intra- and postoperative morbidity in patients with early stage vulvar cancer.
Izvleček
Rak zunanjega spolovila je redka maligna ginekološka bolezen, ki v Sloveniji prizadene približno 57 žensk na leto. Zasevki v 
ingvinalno-femoralnih bezgavkah so najpomembnejši napovedni dejavnik pri lokalizirni in pri lokalno napredovali bolez-
ni. V začetnem stadiju bolezni so le-ti prisotni pri 20–30 % bolnic. To pomeni, da 70–80 % žensk po kirurškem zdravljenju 
nima koristi od ingvinalno-femoralne limfadenektomije, ki je povezana z visoko stopnjo obolevnosti med in po operaciji 
(okužba in dehiscenca rane, limfedem spodnjega uda).
Biopsija varovalne bezgavke pri raku zunanjega spolovila je minimalno invaziven in varen poseg, ki ga je smiselno opraviti 
pri začetnem stadiju bolezni (FIGO stadij IB in II), pri katerem gre za enožariščni tumor, ki v premeru meri manj kot 4 cm, ni 
pa kliničnih/radioloških znakov za razsoj bolezni v ingvinalne bezgavke. S tem se zmanjša obolevnost med operacijo in po 
njej pri ženskah z začetnim stadijem raka zunanjega spolovila.
1 Department of Gyneacological Oncology, Oncology Institute Ljubljana, Ljubljana, Slovenia
2 University Medical Centre Ljubljana, Ljubljana, Slovenia
Correspondence / Korespondenca: Sebastjan Merlo, e: smerlo@onko-i.si
Key words: vulva; sentinel lymph node; lymphadenectomy; lymphoscintigraphy; inguinofemoral lymph nodes
Ključne besede: zunanje spolovilo; varovalna bezgavka; limfadenektomija; limfoscintigrafija; ingvinalno-femoralne bezgavke
Received / Prispelo: 16. 4. 2020 | Accepted / Sprejeto: 29. 7. 2020
Cite as / Citirajte kot: Kovačević N, Drmota E, Merlo S. The role of lymphoscintigraphy and groin sentinel node biopsy in early stage 
vulvar cancer. 2021;90(7–8):403–9. DOI: https://doi.org/10.6016/ZdravVestn.3061
eng slo element
en article-lang
10.6016/ZdravVestn.3061 doi
16.4.2020 date-received
29.7.2020 date-accepted
Obstetrics, gynaecology, andrology, reproduc-
tion, sexuality
Porodništvo, ginekologija, andrologija, reproduk-
cija, spolnost discipline
Professional article Strokovni članek article-type
The role of lymphoscintigraphy and groin sen-
tinel node biopsy in early stage vulvar cancer
Vloga limfoscintigrafije in biopsije varovalne 
bezgavke pri začetnem stadiju raka zunanjega 
spolovila
article-title
The role of lymphoscintigraphy and groin sen-
tinel node biopsy in early stage vulvar cancer
Vloga limfoscintigrafije in biopsije varovalne 
bezgavke pri začetnem stadiju raka zunanjega 
spolovila
alt-title
vulva, sentinel lymph node, lymphadenec-
tomy, lymphoscintigraphy, inguinofemoral 
lymph nodes
zunanje spolovilo, varovalna bezgavka, lim-
fadenektomija, limfoscintigrafija, ingvinalno-fem-
oralne bezgavke
kwd-group
The authors declare that there are no conflicts 
of interest present.
Avtorji so izjavili, da ne obstajajo nobeni 
konkurenčni interesi. conflict
year volume first month last month first page last page
2021 90 7 8 1 7
name surname aff email
Sebastjan Merlo 1 smerlo@onko-i.si
name surname aff
Nina Kovačević 1
Eva Drmota 2
eng slo aff-id
Department of Gyneacological 
Oncology, Oncology Institute 
Ljubljana, Ljubljana, Slovenia
Oddelek za ginekološko 
onkologijo, Onkološki Inštitut 
Ljubljana, Ljubljana, Slovenija
1
University Medical Centre 
Ljubljana, Ljubljana, Slovenia
Univerzitetni klinični center 
Ljubljana, Ljubljana, Slovenija 2
Slovenian Medical Journallovenian Medical Journal
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Zdrav Vestn | July – August 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3061
1 Introduction
Vulvar cancer is a rare disease with an incidence rate 
of 1.5–3 per 100,000 women in Europe (1). In 2016, 57 
women were diagnosed with it in Slovenia (5.5/100,000 
women) (2).
There are two pathways for the onset of the disease. 
In younger patients, the disease is more often associ-
ated with the human papillomavirus (HPV) infection, 
most commonly with strains 16 or 18. In older patients, 
however, onset of the disease does not depend on the 
HPV infection (3). Histologically, 90% of vulvar cancer 
is defined as squamous cell carcinoma (4). It most com-
monly spreads lymphogenically to the inguinofemoral 
lymph nodes. However, in the case of a tumour growth 
in the area of the clitoris or perineum, the literature al-
so describes direct metastasis to the pelvic lymph nodes 
(5).
The most important prognostic factor in the 
non-metastatic form of vulvar cancer is inguinal lymph 
node involvement. In the case of unaffected inguinal 
lymph nodes, the 5-year survival rate is 95%, and in the 
case of lymph node metastases, the 5-year survival rate 
is reduced to 62% (6).
The standard surgical treatment of early stages of 
vulvar cancer (FIGO stage IB/II) without typically en-
larged inguinal lymph nodes was a wide tumour exci-
sion with a safety margin, simple vulvectomy, and uni-
lateral or bilateral inguinofemoral lymphadenectomy. 
Only 20–30% of women with early-stage vulvar cancer 
have metastases present in the inguinal lymph nodes, 
so inguinofemoral lymphadenectomy is not required in 
most of these patients. 70% or more of patients do not 
benefit from additional surgery, while there is a signifi-
cant increase in morbidity and decrease in the quality of 
life due to postoperative complications such as cellulitis, 
lower extremity lymphoedema, and wound dehiscence 
(7). As a result, supplemental irradiation, if planned, 
may also have to be delayed.
Sentinel lymph node biopsy is a minimally invasive 
procedure used to determine the presence of metasta-
ses in the lymph nodes. This is explained by the fact 
that the sentinel lymph node is the first in the chain of 
lymph nodes where the primary tumour drains. Nega-
tive sentinel lymph node biopsy is associated with a low 
incidence of disease recurrence in the inguinofemoral 
region (8,9), with fewer complications during and after 
surgery (8,10), and with shorter duration of surgery and 
hospitalization (11). Today, sentinel lymph node biopsy 
is a safe replacement for inguinofemoral lymphadenec-
tomy in selected women with early-stage vulvar cancer 
(12).
2 Epidemiology
Vulvar cancer accounts for 3–5% of all gynaecolog-
ical cancer cases in the world and is the fourth most 
common gynaecological malignancy. It is estimated 
that about 27,000 women fall ill each year. The highest 
incidences are recorded in Europe, South America and 
North America. The occurrence of this type of cancer in 
Asia and Africa, however, is rare (13,14).
In Slovenia, vulvar cancer accounts for 4% of all cases 
of gynaecological cancer and is one of the rare types of 
cancer, which include all types of cancer with an inci-
dence < 6 per 100,000 population. In 2016, 57 women 
(5.5/100,000 women) fell ill in Slovenia. In the time-
trend analysis of the last 15 years, a significant increase 
in incidence since 2003 is observed, while mortality is 
constant during the entire observation period. This in-
crease in incidence coincides with the introduction of 
ZORA, the National Screening Programme for the Early 
Detection of Precancerous Changes of the Cervix (2). 
We can conclude that this is related to the ageing pop-
ulation and more frequent visits to primary gynaecolo-
gists in the elderly population as well.
Vulvar cancer affects older women, most often wom-
en over the age of 80. A smaller peak in incidence is also 
recorded in women around 55 years of age. According to 
data from 2016, 59.6% of patients were diagnosed with 
a limited stage of the disease, 29.8% with an advanced 
stage of the disease, and 7% with metastasis. In the re-
maining 3.5%, the stage of the cancer was unknown (2).
The survival of patients with vulvar cancer is slightly 
improving over time. The observed 5-year survival rate 
of patients between 2004 and 2009 was 43%, while the 
group of those diagnosed with vulvar cancer in the peri-
od 2010–2016 had a 5-year survival rate of 48% (15). Pa-
tients in whom a localized form of the disease has been 
detected have a significantly longer overall survival rate 
than those who already have a locally advanced cancer 
at the time of diagnosis. For patients between 2010 and 
2016, the 5-year survival rate was observed: for the lo-
calized form of the disease it was 64%, and for the locally 
advanced form, 35%. None of the 8 patients from this 
period who had a systemically advanced disease at the 
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The role of lymphoscintigraphy and groin sentinel node biopsy in early stage vulvar cancer
time of diagnosis or whose stage was not determined 
survived 5 years after diagnosis (15).
The international EUROCARE-5 study shows the 
relative 5-year survival rate for a group of patients with 
vulvar and vaginal cancer. The average European relative 
5-year survival rate in this survey for patients who fell ill 
between 2000 and 2007 was 56%, in Slovenia 60%. The 
best survival rate was in the Netherlands, 65% (16).
3 Aetiopathogenesis
Infection with oncogenic human papillomavirus, 
most commonly strains 16 and 18, plays a key role in 
the development of vulvar squamous cell carcinomas. 
Women with a larger number of sexual partners and 
those who have started having sex early have a higher 
risk of cancer. Similar to cervical cancer, smokers and 
immunocompromised patients are more at risk. Women 
who have already had one of the anogenital cancers and 
women with vulvar cancer in situ are also at higher risk 
(17,18).
There are three pathways of the spread of vulvar 
squamous cell carcinoma. The lymph cancer most com-
monly metastasizes to the inguinofemoral lymph nodes. 
Haematogenous spread as well as direct proliferation are 
rare (5).
4 Assessment of inguinofemoral lymph 
nodes before surgery
There is no reliable diagnostic method for determin-
ing the status of inguinofemoral lymph nodes before 
surgery. As with breast cancer, palpation is the most 
basic method for determining the condition of the in-
guinofemoral lymph nodes due to the superficial po-
sition of the lymph nodes, but the accuracy is only 9% 
before surgery and 55% during surgery (19).
Assessment of lymph node involvement can be per-
formed by ultrasound examination (US) of the ingui-
nal fossae. According to some data, the sensitivity and 
specificity of ultrasound of the lymph nodes in vulvar 
cancer are 76.3% and 91.3%, with positive and negative 
prognostic values of 82.9% and 87.5%. If lymph node in-
volvement is suspected after imaging, a biopsy can be 
performed using the fine- or thick-needle method. Ul-
trasound-guided fine-needle biopsy allows cytological 
examination of the lymph nodes and has an estimat-
ed sensitivity of 80%, specificity of 100%, and negative 
and positive predictive value of 93% and 100% (19-22). 
Pathological lymph nodes have an altered ratio between 
the length and width of the lymph node, are round and 
have an unevenly thickened or no longer visible cortex. 
The most reliable signs of malignant infiltration are pe-
ripheral lymph node blood flow and central necrosis.
Other imaging methods have proven to be less appro-
priate compared to ultrasound. The sensitivity of com-
puted tomography (CT) and its positive predictive value 
are 58% and 58%, while in magnetic resonance imaging 
(MRI) they are only 52% and 46%. The data indicate that 
both MRI and CT are unsuitable tests for determining 
metastases in the inguinofemoral lymph nodes (23-27).
5 Why sentinel lymph node biopsy is the 
standard in treating early-stage vulvar 
cancer today
Surgery is still the basic treatment for the early-stage 
vulvar cancer, but the radicality of the procedure has di-
minished in the last twenty years. Treatment used to in-
clude vulvectomy and inguinofemoral lymphadenecto-
my. Lymphadenectomy is associated with a high rate of 
postoperative complications: surgical wound dehiscence 
(20–40%), lymphocysts, and lower extremity lymphoe-
dema (30–70%) (7,28).
In the early stages of the disease, metastases are found 
in the inguinofemoral lymph nodes in only 20 to 30% of 
patients. The rest of the patients (70% or more) do not 
benefit from the procedure, and there is a significant in-
crease in morbidity and decrease in the quality of life.
The most effective way to reduce morbidity in pa-
tients undergoing surgical treatment for vulvar cancer 
is to remove fewer lymph nodes, thereby minimizing 
lymph duct damage and disruption in lymphatic drain-
age. We should not, however, run the risk of obtaining 
false-negative histological results due to a smaller num-
ber of lymph nodes removed. Mortality from recurrence 
of vulvar cancer is as high as 75% (10).
Vulvar cancer has a predictable course of lymph ducts 
and lymphatic drainage. Therefore, and due to the previ-
ously described facts, the less invasive technique of sen-
tinel lymph node biopsy has been extensively and thor-
oughly investigated. Research has shown that sentinel 
lymph node biopsy in selected women with early-stage 
vulvar cancer is a safe substitute for inguinofemoral 
lymphadenectomy, making it the standard investigation 
(29-32).
Vulvar cancer is a rare disease and treatment depends 
largely on the result of the sentinel lymph node biopsy. 
It is therefore important that operations are carried out 
centrally in all qualified centres (32,33).
At the Institute of Oncology Ljubljana, the first sen-
tinel lymph node biopsies were performed in carefully 
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selected vulvar cancer patients in 2003. In the learning 
process, between the 2003–2006, the procedure was per-
formed in 35 patients. In 10 (28.6%) patients the sentinel 
lymph node was positive, which is in line with publica-
tions in the literature. The 5-year survival rate in patients 
with a negative sentinel lymph node biopsy was 88%. 
In patients with a positive sentinel lymph node biopsy 
and subsequent inguinofemoral lymphadenectomy, the 
5-year survival rate was lower, namely 40%. The data are 
comparable to studies describing the 5-year survival rate 
in the early-stage vulvar cancer, 70–93% in the negative 
sentinel lymph node and 25–41% in the positive sentinel 
lymph node (6,34,35). From 2007 to 2019, a biopsy of 
the sentinel lymph nodes was performed in another 181 
patients with the early-stage vulvar cancer at the Insti-
tute of Oncology Ljubljana. In 48 patients (26.5%) the 
sentinel lymph node was positive and in 133 (73.5%) 
negative. No patient experienced inguinal wound com-
plications after surgery (lymphocysts, lower extremity 
lymphoedema, or wound dehiscence).
6 Indications and contraindications for 
sentinel lymph node biopsy
The sentinel lymph node is defined as the first lymph 
node in the lymphatic basin into which the lymph of the 
primary tumour drains. Histological examination of the 
sentinel lymph node is representative for all other lymph 
nodes in the area. A histologically negative sentinel 
lymph node means the absence of metastases in subse-
quent lymph nodes.
Based on the results of the GROINSS-V and GOG-
173 studies, sentinel lymph node biopsy has become the 
standard diagnostic method in the treatment of women 
with early-stage vulvar cancer (9,34).
Suitable for sentinel lymph node biopsy are women 
with histologically confirmed monofocal vulvar cancer 
of less than 4 cm in diameter, with a depth of invasion 
of more than 1 mm, and where clinically there are no 
metastases present in the inguinofemoral lymph nodes. 
It must also be technically feasible to inject the necessary 
substances into the tumour area (33).
A tumour located 1 cm or more from the midline 
of the vulva is usually drained into the unilateral lym-
phatic system, so a sentinel lymph node biopsy is per-
formed on the same side. Bilateral drainage is required 
for tumours that are central or less than 1 cm from the 
median line. In this case, a biopsy of the sentinel lymph 
node should be performed bilaterally. If the lymph node 
is detected in the lymphoscintigraphy on one side only, 
inguinofemoral lymphadenectomy on the opposite side 
is recommended to avoid a false negative result (12,33).
Patients with a multifocal tumour are not suitable 
candidates for sentinel lymph node biopsy because they 
have a higher incidence of recurrence (10.5%) compared 
to patients with a unifocal tumour (2.3%) (10). Previous 
surgery and excisions of the vulva that could interfere 
with the lymphatic flow in the inguinofemoral region are 
relative contraindications for sentinel lymph node biop-
sy. The decision on the procedure in these cases is made 
for each patient separately (3,35,36). Lymphadenectomy 
is recommended as standard treatment in patients with 
recurrent disease or in patients who have already had an 
inguinofemoral sentinel lymph node biopsy (33,37).
7 The role of lymphoscintigraphy before 
sentinel lymph node biopsy
As a rule, the sentinel lymph node is marked in two 
ways, with a nanocolloid bound to 99mTc (Technetium) 
and with Patent Blue. This method is the most reliable, 
as the sentinel lymph node is found in 97.7% of cases. 
By only injecting Patent Blue, the sentinel lymph node 
is identified in 68.7%, and in 94% only by a nanocolloid 
bound to technetium (39-41).
A colloid bound to technetium (99mTc) is a lymphatic 
radiotracer most commonly used in sentinel lymph node 
biopsy. Technetium is a radionuclide that emits gamma 
rays, has a short half-life and represents a low radiation 
burden for both the patient and the medical staff. The 
most commonly used colloid in Europe is the nanocol-
loid albumin (40,41). 
The most modern tracers today are hybrids, indo-
caine (ICG-) and a nanocolloid bound to 99mTc, which 
allow the simultaneous application of both radiophar-
maceutical and fluorescent dye. This makes preoperative 
lymphoscintigraphy and interoperative visualization of 
the sentinel lymph node possible (39).
At the Institute of Oncology Ljubljana, the technique 
has changed and improved over the years. Optimal results 
are achieved if the Patent Blue is injected intradermally 
in a volume of 2 ml. In the morning of the day of surgery, 
0.5 mL 30–100 MBq of technetium-labelled nanocolloid 
is injected with a thin needle into the skin at four points 
near the outer edge of the tumour. This is followed by 
lymphoscintigraphy with a gamma camera. The first ac-
tive accumulation point of radiopharmaceuticals is the 
sentinel lymph node, so its position is marked on the 
skin. Sometimes, several points of high activity appear. 
In this case, we mark all the points. Immediately before 
the beginning of the surgical procedure, 2 ml of Patent 
Blue is injected into the skin in the same place where the 
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The role of lymphoscintigraphy and groin sentinel node biopsy in early stage vulvar cancer
radiopharmaceutical was injected. Then a 3 to 4 cm long 
skin incision is made at the marked site, carefully dissect-
ing the tissue until a blue-stained lymph node is found. 
Its activity is checked with a hand-held gamma detector. 
If the next blue-stained lymph node with lower activity is 
found, it is removed as well. This is followed by removal 
of the tumour on the vulva with a wide safety margin.
8 Ultrastaging of the sentinel lymph node
Careful examination of the sentinel lymph nodes in 
vulvar cancer is crucial because further treatment de-
pends on it. A false-negative histopathological result of 
a sentinel lymph node biopsy leads to the omission of 
further surgery – lymphadenectomy, which triggers the 
rapid growth of metastases present in the lymph nodes 
(44).
Ultrastaging is a procedure used by pathologists to 
carefully examine a small number of lymph nodes. In 
classic inguinofemoral lymphadenectomy, an average of 
9–10 lymph nodes are removed, so ultrastaging is im-
practical and rarely performed. In a sentinel lymph node 
biopsy, however, 1 or 2 lymph nodes are removed and ul-
trastaging is the standard procedure. Paraffin blocks with 
a thickness of 400–500 microM (2–3 mm at a classical 
examination) are stained with haematoxylin and eosin 
and immunohistochemically with cytokeratin, which al-
lows the identification of micrometastasis.
In the lymph nodes, which are negative at a routine 
histopathological examination, ultrastaging shows mi-
crometastasis in 12–42% of cases (43,44).
Examination of the lymph node by the frozen sec-
tion method is not appropriate because it destroys the 
lymph node and prevents its further examination (e.g. 
ultrastaging).
9 Recurrence of the disease inguinally 
after the biopsy of the sentinel lymph 
nodes
In complete inguinofemoral lymphadenectomy, 
which involves dissection of large vessels and, if neces-
sary, transposition of the sartorius muscle, the disease 
recurs in the inguinal fossa in 1% or less. The number 
of complications after this type of surgery is acceptable, 
and they occur mainly in the form of postoperative 
wound dehiscence and lower extremity lymphoedema 
(47). In superficial inguinofemoral lymphadenectomy, 
the disease recurs in 5–7%, which is historically unac-
ceptably high compared to complete lymphadenectomy 
(48). After the removal of the sentinel inguinal lymph 
node, there is a recurrence of the disease inguinally in 
less than 3%, which is an acceptable risk given the low 
incidence rate compared to the morbidity after complete 
inguinofemoral lymphadenectomy (32).
10 Follow-up of patients with vulvar 
cancer after sentinel lymph node biopsy
There is currently not enough reliable evidence to 
support a uniform follow-up scheme for patients after 
early-stage vulvar cancer treatment. Local relapses can 
occur at any time, so close tracking, which is generally 
recommended for life, is crucial. After the primary sur-
gical treatment, the first examination is performed after 
2–8 weeks, followed by clinical examinations of the vul-
va and groin every 3–4 months for a period of two years. 
In the next three years examinations take place twice a 
year. At the end of this period, it makes sense to continue 
with annual clinical examinations (8,47).
11 Conclusion
With the development of a minimally invasive sur-
gical technique for sentinel lymph node biopsy and the 
introduction of this method into the standard treatment 
of vulvar cancer, a major step has been taken to reduce 
morbidity and increase the quality of life of vulvar can-
cer patients. The proportion of patients in whom in-
guinofemoral dissection was performed unnecessarily 
decreased significantly. Finally, it should be emphasized 
again that vulvar cancer is a rare type of cancer. There-
fore, it is sensible and necessary to treat patients in cen-
tres with a larger number of such cases and where the 
necessary logistics and knowledge are provided.
Conflict of interest
None declared.
References
1. Kang YJ, Smith M, Barlow E, Coffey K, Hacker N, Canfell K. Vulvar cancer 
in high-income countries: increasing burden of disease. Int J Cancer. 
2017;141(11):2174-86. DOI: 10.1002/ijc.30900 PMID: 28730615
2. Zadnik V. Rak v Sloveniji 2016 = Cancer in Slovenia. Ljubljana: Onkološki 
inšitut Ljubljana, Epidemiologija in register raka; 2016 [cited 2021 Mar 
7]. Available from: https://www.onko-i.si/fileadmin/onko/datoteke/
dokumenti/RRS/LP_2016.pdf.
408
OBSTETRICS, GYNAECOLOGY, ANDROLOGY, REPRODUCTION, SEXUALITY
Zdrav Vestn | July – August 2021 | Volume 90 | https://doi.org/10.6016/ZdravVestn.3061
3. Del Pino M, Rodriguez-Carunchio L, Ordi J. Pathways of vulvar 
intraepithelial neoplasia and squamous cell carcinoma. Histopathology. 
2013;62(1):161-75. DOI: 10.1111/his.12034 PMID: 23190170
4. Hacker NF, Eifel PJ, van der Velden J. Cancer of the vulva. Int J Gynaecol 
Obstet. 2015;131:S76-83. DOI: 10.1016/j.ijgo.2015.06.002 PMID: 26433678
5. Iversen T, Aas M. Lymph drainage from the vulva. Gynecol Oncol. 
1983;16(2):179-89. DOI: 10.1016/0090-8258(83)90092-6 PMID: 6226578
6. Burger MP, Hollema H, Emanuels AG, Krans M, Pras E, Bouma J. The 
importance of the groin node status for the survival of T1 and T2 vulval 
carcinoma patients. Gynecol Oncol. 1995;57(3):327-34. DOI: 10.1006/
gyno.1995.1151 PMID: 7774836
7. Gaarenstroom KN, Kenter GG, Trimbos JB, Agous I, Amant F, Peters AA, 
et al. Postoperative complications after vulvectomy and inguinofemoral 
lymphadenectomy using separate groin incisions. Int J Gynecol Cancer. 
2003;13(4):522-7. DOI: 10.1136/ijgc-00009577-200307000-00019 PMID: 
12911732
8. Robison K, Roque D, McCourt C, Stuckey A, DiSilvestro PA, Sung CJ, et 
al. Long-term follow-up of vulvar cancer patients evaluated with sentinel 
lymph node biopsy alone. Gynecol Oncol. 2014;133(3):416-20. DOI: 
10.1016/j.ygyno.2014.03.010 PMID: 24631445
9. Te Grootenhuis NC, van der Zee AG, van Doorn HC, van der Velden 
J, Vergote I, Zanagnolo V, et al. Sentinel nodes in vulvar cancer: Long-
term follow-up of the GROningen INternational Study on Sentinel nodes 
in Vulvar cancer (GROINSS-V) I. Gynecol Oncol. 2016;140(1):8-14. DOI: 
10.1016/j.ygyno.2015.09.077 PMID: 26428940
10. Van der Zee AG, Oonk MH, De Hullu JA, Ansink AC, Vergote I, Verheijen RH, 
et al. Sentinel node dissection is safe in the treatment of early-stage vulvar 
cancer. J Clin Oncol. 2008;26(6):884-9. DOI: 10.1200/JCO.2007.14.0566 
PMID: 18281661
11. McCann GA, Cohn DE, Jewell EL, Havrilesky LJ. Lymphatic mapping 
and sentinel lymph node dissection compared to complete 
lymphadenectomy in the management of early-stage vulvar cancer: A 
cost-utility analysis. Gynecol Oncol. 2015;136(2):300-4. DOI: 10.1016/j.
ygyno.2014.11.079 PMID: 25478927
12. Koh WJ, Greer BE, Abu-Rustum NR, Campos SM, Cho KR, Chon HS, et 
al. Vulvar Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in 
Oncology. J Natl Compr Canc Netw. 2017;15(1):92-120. DOI: 10.6004/
jnccn.2017.0008 PMID: 28040721
13. Bodelon C, Madeleine MM, Voigt LF, Weiss NS. Is the incidence of invasive 
vulvar cancer increasing in the United States? Cancer Causes Control. 
2009;20(9):1779-82. DOI: 10.1007/s10552-009-9418-8 PMID: 19680749
14. Lai J, Elleray R, Nordin A, Hirschowitz L, Rous B, Gildea C, et al. Vulval 
cancer incidence, mortality and survival in England: age-related trends. 
BJOG. 2014;121(6):728-38. DOI: 10.1111/1471-0528.12459 PMID: 24148762
15. Epidemiologija in register raka. Slora. Slovenija in rak. Ljubljana: 
Onkološki inštitut; 2017 [cited 2021 Mar 7]. Available from: http://www.
slora.si/en/incidenca.
16. De Angelis R, Sant M, Coleman MP, Francisci S, Baili P, Pierannunzio D, 
et al.; EUROCARE-5 Working Group. Cancer survival in Europe 1999-2007 
by country and age: results of EUROCARE—5-a population-based study. 
Lancet Oncol. 2014;15(1):23-34. DOI: 10.1016/S1470-2045(13)70546-1 
PMID: 24314615
17. Rakislova N, Saco A, Sierra A, Del Pino M, Ordi J. Role of Human 
Papillomavirus in Vulvar Cancer. Adv Anat Pathol. 2017;24(4):201-14. DOI: 
10.1097/PAP.0000000000000155 PMID: 28590952
18. van de Nieuwenhof HP, van Kempen LC, de Hullu JA, Bekkers RL, Bulten 
J, Melchers WJ, et al. The etiologic role of HPV in vulvar squamous 
cell carcinoma fine tuned. Cancer Epidemiol Biomarkers Prev. 
2009;18(7):2061-7. DOI: 10.1158/1055-9965.EPI-09-0209 PMID: 19567503
19. Mäkelä PJ, Leminen A, Kääriäinen M, Lehtovirta P. Pretreatment 
sonographic evaluation of inguinal lymph nodes in patients with 
vulvar malignancy. J Ultrasound Med. 1993;12(5):255-8. DOI: 10.7863/
jum.1993.12.5.255 PMID: 8345551
20. Angelico G, Santoro A, Inzani F, Spadola S, Fiorentino V, Cianfrini F, et 
al. Ultrasound-guided FNA cytology of groin lymph nodes improves the 
management of squamous cell carcinoma of the vulva: results from a 
comparative cytohistological study. Cancer Cytopathol. 2019;127(8):514-
20. DOI: 10.1002/cncy.22154 PMID: 31174235
21. Hall TB, Barton DP, Trott PA, Nasiri N, Shepherd JH, Thomas JM, et al. 
The role of ultrasound-guided cytology of groin lymph nodes in the 
management of squamous cell carcinoma of the vulva: 5-year experience 
in 44 patients. Clin Radiol. 2003;58(5):367-71. DOI: 10.1016/S0009-
9260(02)00575-5 PMID: 12727164
22. de Gregorio N, Ebner F, Schwentner L, Friedl TW, Deniz M, Látó K, et al. 
The role of preoperative ultrasound evaluation of inguinal lymph nodes 
in patients with vulvar malignancy. Gynecol Oncol. 2013;131(1):113-7. 
DOI: 10.1016/j.ygyno.2013.07.103 PMID: 23932893
23. Singh K, Orakwue CO, Honest H, Balogun M, Lopez C, Luesley DM. 
Accuracy of magnetic resonance imaging of inguinofemoral lymph nodes 
in vulval cancer. Int J Gynecol Cancer. 2006;16(3):1179-83. DOI: 10.1136/
ijgc-00009577-200605000-00035 PMID: 16803503
24. Bipat S, Fransen GA, Spijkerboer AM, van der Velden J, Bossuyt PM, 
Zwinderman AH, et al. Is there a role for magnetic resonance imaging 
in the evaluation of inguinal lymph node metastases in patients with 
vulva carcinoma? Gynecol Oncol. 2006;103(3):1001-6. DOI: 10.1016/j.
ygyno.2006.06.009 PMID: 16859737
25. Kataoka MY, Sala E, Baldwin P, Reinhold C, Farhadi A, Hudolin T, et al. 
The accuracy of magnetic resonance imaging in staging of vulvar cancer: 
a retrospective multi-centre study. Gynecol Oncol. 2010;117(1):82-7. DOI: 
10.1016/j.ygyno.2009.12.017 PMID: 20092880
26. Andersen K, Zobbe V, Thranov IR, Pedersen KD. Relevance of 
computerized tomography in the preoperative evaluation of patients 
with vulvar cancer: a prospective study. Cancer Imaging. 2015;15(1):8. 
DOI: 10.1186/s40644-015-0044-2 PMID: 26059775
27. Land R, Herod J, Moskovic E, King M, Sohaib SA, Trott P, et al. Routine 
computerized tomography scanning, groin ultrasound with or without 
fine needle aspiration cytology in the surgical management of 
primary squamous cell carcinoma of the vulva. Int J Gynecol Cancer. 
2006;16(1):312-7. DOI: 10.1111/j.1525-1438.2006.00340.x PMID: 16445651
28. Kirby TO, Rocconi RP, Numnum TM, Kendrick JE, Wright J, Fowler W, et 
al. Outcomes of Stage I/II vulvar cancer patients after negative superficial 
inguinal lymphadenectomy. Gynecol Oncol. 2005;98(2):309-12. DOI: 
10.1016/j.ygyno.2005.05.011 PMID: 15975642
29. Slomovitz BM, Coleman RL, Oonk MH, van der Zee A, Levenback C. 
Update on sentinel lymph node biopsy for early-stage vulvar cancer. 
Gynecol Oncol. 2015;138(2):472-7. DOI: 10.1016/j.ygyno.2015.05.017 
PMID: 26022527
30. Oonk MH, Hollema H, van der Zee AG. Sentinel node biopsy in vulvar 
cancer: implications for staging. Best Pract Res Clin Obstet Gynaecol. 
2015;29(6):812-21. DOI: 10.1016/j.bpobgyn.2015.03.007 PMID: 25962357
31. Zigras T, Kupets R, Barbera L, Covens A, Liu Y, Gien LT. Uptake of sentinel 
lymph node procedures in women with vulvar cancer over time in 
a population based study. Gynecol Oncol. 2019;153(3):574-9. DOI: 
10.1016/j.ygyno.2019.03.010 PMID: 30876675
32. Brincat MR, Muscat Baron Y. Sentinel Lymph Node Biopsy in the 
Management of Vulvar Carcinoma: An Evidence-Based Insight. Int J 
Gynecol Cancer. 2017;27(8):1769-73. DOI: 10.1097/IGC.0000000000001075 
PMID: 28763369
33. Oonk MH, Planchamp F, Baldwin P, Bidzinski M, Brännström M, Landoni 
F, et al. European Society of Gynaecological Oncology Guidelines for 
the Management of Patients With Vulvar Cancer. Int J Gynecol Cancer. 
2017;27(4):832-7. DOI: 10.1097/IGC.0000000000000975 PMID: 28441255
34. Maggino T, Landoni F, Sartori E, Zola P, Gadducci A, Alessi C, et al. 
Patterns of recurrence in patients with squamous cell carcinoma of 
the vulva. A multicenter CTF Study. Cancer. 2000;89(1):116-22. DOI: 
10.1002/1097-0142(20000701)89:1<116::AID-CNCR16>3.0.CO;2-4 PMID: 
10897008
409
PROFESSIONAL ARTICLE
The role of lymphoscintigraphy and groin sentinel node biopsy in early stage vulvar cancer
35. Gadducci A, Cionini L, Romanini A, Fanucchi A, Genazzani AR. Old and 
new perspectives in the management of high-risk, locally advanced 
or recurrent, and metastatic vulvar cancer. Crit Rev Oncol Hematol. 
2006;60(3):227-41. DOI: 10.1016/j.critrevonc.2006.06.009 PMID: 16945551
36. Levenback CF, Ali S, Coleman RL, Gold MA, Fowler JM, Judson PL, et al. 
Lymphatic mapping and sentinel lymph node biopsy in women with 
squamous cell carcinoma of the vulva: a gynecologic oncology group 
study. J Clin Oncol. 2012;30(31):3786-91. DOI: 10.1200/JCO.2011.41.2528 
PMID: 22753905
37. Crosbie EJ, Winter-Roach B, Sengupta P, Sikand KA, Carrington B, Murby 
B, et al. The accuracy of the sentinel node procedure after excision biopsy 
in squamous cell carcinoma of the vulva. Surg Oncol. 2010;19(4):e150-4. 
DOI: 10.1016/j.suronc.2010.08.003 PMID: 20833535
38. Levenback C, Coleman RL, Burke TW, Bodurka-Bevers D, Wolf JK, 
Gershenson DM. Intraoperative lymphatic mapping and sentinel node 
identification with blue dye in patients with vulvar cancer. Gynecol Oncol. 
2001;83(2):276-81. DOI: 10.1006/gyno.2001.6374 PMID: 11606084
39. van Doorn HC, van Beekhuizen HJ, Gaarenstroom KN, van der Velden J, 
van der Zee AG, Oonk MH, et al. Repeat sentinel lymph node procedure 
in patients with recurrent vulvar squamous cell carcinoma is feasible. 
Gynecol Oncol. 2016;140(3):415-9. DOI: 10.1016/j.ygyno.2016.01.013 
PMID: 26797295
40. Verbeek FP, Tummers QR, Rietbergen DD, Peters AA, Schaafsma BE, van 
de Velde CJ, et al. Sentinel Lymph Node Biopsy in Vulvar Cancer Using 
Combined Radioactive and Fluorescence Guidance. Int J Gynecol Cancer. 
2015;25(6):1086-93. DOI: 10.1097/IGC.0000000000000419 PMID: 25768079
41. Mathéron HM, van den Berg NS, Brouwer OR, Kleinjan GH, van Driel 
WJ, Trum JW, et al. Multimodal surgical guidance towards the sentinel 
node in vulvar cancer. Gynecol Oncol. 2013;131(3):720-5. DOI: 10.1016/j.
ygyno.2013.09.007 PMID: 24051219
42. Collarino A, Fuoco V, Garganese G, Pereira Arias-Bouda LM, Perotti G, 
Manca G, et al. Lymphoscintigraphy and sentinel lymph node biopsy 
in vulvar carcinoma: update from a European expert panel. Eur J Nucl 
Med Mol Imaging. 2020;47(5):1261-74. DOI: 10.1007/s00259-019-04650-8 
PMID: 31897584
43. Giammarile F, Bozkurt MF, Cibula D, Pahisa J, Oyen WJ, Paredes P, et al. 
The EANM clinical and technical guidelines for lymphoscintigraphy and 
sentinel node localization in gynaecological cancers. Eur J Nucl Med 
Mol Imaging. 2014;41(7):1463-77. DOI: 10.1007/s00259-014-2732-8 PMID: 
24609929
44. Ayhan A, Celik H, Dursun P. Lymphatic mapping and sentinel node biopsy 
in gynecological cancers: a critical review of the literature. World J Surg 
Oncol. 2008;6(1):53. DOI: 10.1186/1477-7819-6-53 PMID: 18492253
45. Cormio G, Loizzi V, Carriero C, Cazzolla A, Putignano G, Selvaggi L. Groin 
recurrence in carcinoma of the vulva: management and outcome. 
Eur J Cancer Care (Engl). 2010;19(3):302-7. DOI: 10.1111/j.1365-
2354.2008.01011.x PMID: 19832900
46. Narayansingh GV, Miller ID, Sharma M, Welch CJ, Sharp L, Parkin DE, et 
al. The prognostic significance of micrometastases in node-negative 
squamous cell carcinoma of the vulva. Br J Cancer. 2005;92(2):222-4. DOI: 
10.1038/sj.bjc.6602343 PMID: 15655537
47. Oonk MH, van Hemel BM, Hollema H, de Hullu JA, Ansink AC, Vergote 
I, et al. Size of sentinel-node metastasis and chances of non-sentinel-
node involvement and survival in early stage vulvar cancer: results 
from GROINSS-V, a multicentre observational study. Lancet Oncol. 
2010;11(7):646-52. DOI: 10.1016/S1470-2045(10)70104-2 PMID: 20537946
48. Stehman FB, Bundy BN, Dvoretsky PM, Creasman WT. Early stage I 
carcinoma of the vulva treated with ipsilateral superficial inguinal 
lymphadenectomy and modified radical hemivulvectomy: a 
prospective study of the Gynecologic Oncology Group. Obstet Gynecol. 
1992;79(4):490-7. PMID: 1553164
49. Merlo S. Priporočila za obravnavo bolnic z rakom zunanjega spolovila. 
Ljubljana: Onkološki inštitut; 2020.