Vulvar cancer is a rare malignancy that constitutes about 5% of female genital tract cancers. It most commonly affects older women around age 68. About 40% of cases are linked to HPV infection. Sentinel lymph node biopsy is an important diagnostic technique to detect early metastatic spread. Studies have found the sentinel lymph node to be accurate in detecting metastases in over 90% of cases, with a low false negative rate of around 3-8%. Positive sentinel nodes are associated with higher rates of recurrence and worse survival outcomes. Sentinel lymph node biopsy provides valuable staging information with less morbidity compared to traditional inguinal lymphadenectomy.

1. Staging,Pathogenesis,Diagnosis
Sentinel Lymph node biopsy of Vulvar
Cancer
Dr. Bhavin P.Vadodariya,
Resident Doctor in Surgical Oncology,
Apollo CBCC Cancer Care,
Ahmedabad
Date-24/02/18

2. Incidence
 Constitutes
 5% of all the malignancies of female genital tract
 0.6% of female cancer
 Estimated new cases and deaths from vulval cancer in the
United States in 2015
 New cases: 5150
 Deaths: 1080
 Rare malignancy (28th) in the United States and accounts for
0.3% of all new cancers.
Cancer Facts and Figures 2015.Atlanta
American Cancer Society,2015.

3. SEER Stat Fact
Sheets:
Vulval cancer
 Lifetime Risk of Developing Cancer : Approximately
0.3 percent
 0.2% of all cancer deaths (Estimated).
 5-years survival rate of 71.2%
Based on2010-2012 data

5. TRENDS IN
RATES Using statistical models for analysis, rates for new vulvar cancer cases
have been rising on average 0.5% each year over the last 10 years.
Death rates have not changed significantly over 2002-2012.
SEER 9 Incidence & U.S. Mortality 1975-2012, All Races,
Females.
Rates are Age-Adjusted.

6. Age
 A disease of older women.
 Delayed diagnosis is typical, despite vulva being an external
organ.
 Vulvar cancer is most frequently diagnosed among women
aged 75-84.
 Median Age at Diagnosis is 68 years.
SEER Stat Fact Sheets: Vulval cancer,
2014

7. Etiology - HPV
 Approximately, 40% vulvar cancers are HPV (Human Papilloma
Virus) Positive.
 Of these HPV positive invasive vulvar cancers – 85% are attributed to
HPV 16.
 Prophylactic HPV vaccines have the potential to decrease the
incidence of invasive vulvar cancer by about one-third overall, and to
be even more effective in younger women.
Smith JS et al.
Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their
Associated Precursors
Obstet Gynecol. 2009; 113:917-24

8. Etiology – Vulval
Intraepithelial Neoplasia (VIN)
 The International Society for the Study of Vulvovaginal Disease
(ISSVD) in 2004 officially divided VIN into two types:
 VIN Usual Type – HPV infection related (warty/ basaloid
/mixed)
 VIN Differentiated Type - unrelated to HPV infection
 The older classification of VIN 1, 2, and 3 was based on the degree
of histologic abnormality, but there is no evidence that
 the VIN 1 to 3 morphologic spectrum reflects a biologic
continuum,
 or that VIN 1 is a cancer precursor

9. Etiology – Vulval
Intraepithelial Neoplasia (VIN)
 There has been a significant increase in the incidence of vulvar
intraepithelial Neoplasia (VIN) in recent decades, and this has been
attributed to
 changing sexual behavior ,
 human papillomavirus (HPV) infection, and
 cigarette smoking.

10.  In a study designed to investigate the malignant potential of
the vulvar premalignant conditions, Eva et al. identified 580 women
from Birmingham, England, who had vulvar biopsies showing VIN,
lichen sclerosus, or Squamous hyperplasia over a 5-year period.
These women were studied for the presence of a synchronous or
metachronous vulvar cancer.
 differentiated VIN had a higher risk of malignancy (85.7%) than
 usual VIN (25.8%),
 lichen sclerosus (27.7%) or
 Squamous hyperplasia (31.7%).
Eva et al.
Differentiated type VIN has a high-risk association with vulval
squamous cell carcinoma
Int J Gynecol Cancer 2009;19:741-744

11. Etiology
 The increased risk of a subsequent cancer to be 1.3-fold.
 Most of the second cancers were related to
 smoking (i.e., cancers of the lung, buccal cavity , pharynx,
nasal cavity , or larynx) or
 human papillomavirus infections (e.g., cervix, vagina, or
anus).

13. Basloid or warty type
 multifocal
 In younger
 Related to HPV infection
 Vulvar Intraepithelial
Neoplasia
 Cigarette smoking
Keratinizing type
 Unifocal
 In older
 Not related to HPV
 In area adjacent to lichen
sclerosis and Squamous
hyperplasia(80%)
 VIN uncommon -
Differentiated type
Type
s

15. Pathology
 Squamous cell carcinoma = 85–90%
 Basal cell, Invasive paget’s disease, bartholin glands Ca,
Sarcoma

16. SURVIVA
L Historically, (in early 20th century) – presentation with
advanced diseases.
 5-years survival – 20-25% ONLY
 Radical en-bloc dissection by Taussig - US (1940) and Way -
Britain (1960) – Improved survival of 60-70%. (High post-
operative morbidities –
 wound breakdown, infection, and
 prolonged hospitalization,
 pelvic exenteration- for patients with disease involving the anus,
rectum, or proximal urethra)

17. Survival
 Overall 5 years survival rate in USA is 71.2%
Based on data from SEER 18 2005-2011
 The earlier vulvar cancer is diagnosed, the better chance a
person has of surviving five years after being diagnosed.

18.  For vulvar cancer, 59.2% are diagnosed at the local stage.
 The 5-year survival for localized vulvar cancer is 85.8%.

19. CARCINOMAS OF THE VULVA
19
HISTOPATHOLOGIC GRADING: -
 Differentiated carcinoma: begins at the surface and presents a pattern of
broad buds with rounded borders composed of well-differentiated tumour
cells that contain abundant cytoplasm, keratin, keratohyaline granules, and
intercellular bridges.
 Poorly differentiated carcinoma: is generally found at the epithelial stromal
junction. It is characterized by small tumor cells with scant cytoplasm
showing little or no differentiation that infiltrates the stroma either in
elongated streaks or small clusters (spray pattern).

20. CARCINOMAS OF THE VULVA
20
 Poorly differentiated component occupies less than or equal to 25%
of the total area of the tumor.
 Grade 3:
 Poorly differentiated component occupies greater than 25%, but less
than or equal to 50% of the total area of the tumour.
 Grade 4:
 Poorly differentiated component occupies greater than 50% of the
tumour area.
HISTOPATHOLOGIC GRADING: -
 Grade 1:
 No poorly differentiated component.
 Grade 2:

21. CARCINOMAS OF THE VULVA
21

 Ninety per cent of these epithelial malignant tumours are
squamous cell carcinomas, the remainder being basal cell
carcinomas, melanomas, or adenocarcinomas
 The malignant melanoma should be reported seperately

22. Cases should be classified as carcinoma of the vulva
when the primary site of the growth is in the vulva.
Tumours present in the vulva as secondary growth
from either a genital or extra-genital site should
be
excluded.
A carcinoma of the vulva that has extended to the
vagina should be considered as a carcinoma of the
vulva.

23. Squamous Cell Carcinoma of Vulva
23


 Risk of metastatic spread is linked to the size of
tumour, depth of invasion, and involvement of
lymphatic vessels.
The inguinal, femoral, pelvic, iliac, and periaortic lymph
nodes are most commonly involved. Ultimately,
lymphohematogenous dissemination involves the lungs,
liver, and other internal organs.

24. Patients with lesions less than 2 cm in diameter have a 60% to 80% 5-
year survival rate after treatment with one-stage vulvectomy and
lymphadenectomy; larger lesions with lymph node involvement yield a
less than 10% 5-year survival rate.

25. Verrucous carcinoma of vulva
25
 An uncommon variant of squamous cell carcinoma with low
malignant potential.
 It may, however, grow very large.
 These lesions were originally described as occurring in the
oral cavity but have also been described involving the
vagina, cervix, and vulva.
 Clinically, these tumours are very slow growing and carry
an excellent prognosis.
 The lesion grossly appears cauliflower-like in nature.

26. Verrucous carcinoma of vulva
26
 This rare variant of squamous cell carcinoma may also
resemble condyloma acuminatum and present as a large
fungating tumor.

27. Verrucous carcinoma of vulva
27
 Local invasion confirms the malignant nature of the lesion, but
it rarely metastasises and can be cured by wide excision.
 If there are suspicious groin nodes, FNA or
excisional biopsy should be carried out.

28. Paget’s Disease of Vulva
28
 Rare lesion of the vulva, and sometimes the perianal
region, is similar in its skin manifestations to Paget
disease of the breast.
 As a vulvar neoplasm, it manifests as a pruritic red, crusted,
sharply demarcated, map like area, occurring usually on the
labia majora. It may be accompanied by a palpable
submucosal thickening or tumor.

31. Paget’s Disease of Vulva
31



 In contrast to Paget’s disease of the nipple, in which
100% of patients show an underlying ductal breast
carcinoma, vulvar lesions are most frequently
confined to the epidermis of the skin and adjacent
hair follicles and sweat glands.

32. Paget’s Disease of Vulva
The prognosis of Paget’s disease is poor in the uncommon
cases with associated carcinoma, but intraepidermal Paget’s
disease may persist for many years, even decades, without the
development of invasion.
However, because Paget’s cells often extend into skin
appendages and may extend beyond the confines of the
grossly visible lesion, they are prone to recurrence.
It is considered as nothing more than a variant of VIN

33. Paget’s Disease of Vulva
33


The diagnostic microscopic feature of this lesion is the
presence of Paget cells, large tumor cells lying singly or in
small clusters within the epidermis and its appendages.
These cells are distinguished by a clear separation ("halo")
from the surrounding epithelial cells and a finely granular
cytoplasm containing periodic acid-Schiff stain-, Alcian blue-,
or mucicarmine-positive mucopolysaccharide.
Ultrastructurally, Paget cells display apocrine, eccrine, and
keratinocyte differentiation and presumably arise from
primitive epithelial progenitor cells.

34. Malignant Melanoma
34



Melanomas of the vulva are rare, representing less than
5% of all vulvar cancers and 2% of all melanomas in
women.
Their peak incidence is in the sixth or seventh decade;

35. Malignant Melanoma
They tend to have the same biologic and histologic
characteristics as melanomas occurring elsewhere
and are capable of widespread metastatic
dissemination.
Because it is initially confined to the epithelium,
melanoma may resemble Paget’s disease, both
grossly and histologically.

36. Malignant Melanoma
36


It can usually be differentiated by its uniform reactivity,
with immunoperoxidase techniques, with antibodies to
S100 protein, absence of reactivity with antibodies to
carcinoembryonic antigen, and lack of
mucopolysaccharides.

37. Malignant Melanoma
Prognosis is linked principally to depth of invasion,
with greater than 60% mortality for lesions invading
deeper than 1 mm.
The overall survival rate is less than 32%, presumably
owing to delays in detection and a generally poor
prognosis for mucosal melanomas.

38. Basal cell carcinoma
38
 Vulva is a very unusual site for this lesion.
 When it occurs, its features are similar to rodent ulcer
of the face.
 This is an invasive squamous cell carcinoma, which
penetrates into the dermis and deeper tissues.
 Its spread is slow and it does not
metastasizes,
 Local excision is curative.

39. Diagnostic Evaluation

40. Physcial examination
•Measurements of primary tumour
•Assesment of extension to adjacent mucosal and bony
structures
•Distance from vital structures,,e.g urethra,anus,clitoris

41. Punch biopsy
For diagnosis and to know DOI
Inguinal node FNAC or Biopsy if it can change the plan

42. Diagnsotic imaging
Required in obese women to identify lymphnodes

43. EUA,Cystourethroscopy or
Proctosigmoidoscopy
Large fixed tumors

44. PAP smear
Etiology is same.
All women with vulval cancer should undergo pap smear
De bie et al.,British journal of
cancer 2009

47. SENTINEL LYMPHNODE
MAPPING

48. Prognostic Factors
•Demogrpahical Risk Factors
•Tumor Factors
•Size,location,DOI, Laterality , LVSI
•Inguinal nodes
•Distant metastasis

51.  First draining lymph-node in the lymphatic basin that recieves primary
lymph flow from the tumor.
 Use of comprehensive serial sectioning, Immunohistochemistry (IHC), and
reverse transcription-polymerase chain reaction have been investigated as
potential methods to detect the earliest signs of metastatic disease.

52. Sentinel lymph node biopsy (SLNB) represents the
largest
innovation in the care of patients with vulvar cancer
in the past
decade.

53. PROCEDURE
 1-2mlof isosulfan blue dye or 400mCi of technetium labeled sulfur
colloid injected circumferentially intradermally around the
tumor, and lymphoscintigraphy was performed.
 The sites of the SLNs marked on the skin with a pencil.
 SLNs identified using a handheld probe and the dissection of blue-
stained lymph vessels and lymph nodes.

54.  Intra operative gamma counter to identify for identification of the
nodes and lymphatics.
 The removed SLNs sent to the pathologist separately.
 Ultrastaging consisted of performing serial sectioning and IHC
analysis with cytokeratins.

56. GROINNS – V- I

61. Sentinel lymph node biopsy is a reasonable alternative to inguinal
femoral
lymphadenectomy in
selected women with squamous cell carcinoma of the
STUDIES Details
GROINSS-V 403patients
26% metastatic
sentinel nodes
3% groin recurrences
GOG-173 452 women underwent
the planned
procedures, 418 had
at least one
sentinel lymph
132 node-positive women
11 (8.3%) with false-
negative
23% true positive
detected by IHC
sensitivity was 91.7%
False-negative
predictive value 3.7%

65. Variables SN -Ve SN +ve
Local recurrence at 5
yr
24.6% 33.2%
Local recurrence at
10 yr
36.4% 46.4%
Isolated groin
recurrences at 5
years
2.5% 8%
Disease specific
survival rate at 10
91% 65%

70.  Reliance on the SLN is dependent on
 accurate injection of the blue dye and/or radioisotope,
 interpretation of the preoperative lymphoscintigraphy, and
 proper handling of the node by the pathologist, including serial
sectioning and IHC analysis.
 Implementation in the routine treatment of early-stage vulvar
cancer requires quality control at each step of this multidisciplinary
procedure.

71.  Learning curve associated with the SLN procedure
 Success of the procedure is surgeon dependent (requires a
surgeon with successful experience SLN procedure followed
by full lymphadenectomy in at least 10 patients.) Finally, to
keep the experience at a high level, an exposure of at least
5–10 SLN procedures per year per surgeon is likely
necessary.
 In a rare tumor such as vulvar cancer, this requires
centralization of early stage vulvar cancer treatment in
oncology centers

72. Take Home message
1. Invasive vulvar cancer is a relatively rare tumor,
accounting for 4% of all female genital malignant
neoplasms.
2. Squamous cell carcinoma of the vulva develops by
human papillomavirus- (HPV-) dependent and HPV-
independent pathways.
3. Sentinel lymph node biopsy represents the largest
innovation in the care of vulvar cancer patients in
the past decade.

73. SLNB Take home
•Clearly, the current approach to the management of
patients with vulvar cancer is far from settled.
•The criteria for preoperative evaluation are not
standardized
•The surgeon's learning curve is critical in determining the
success of the procedure
• Yet to set definitive standards with regard to the
management of isolated tumor cells or micrometastases
found in the sentinel node in vulvar cancer