Herpes Vulvitis

22/02/53 

Clitoral hood 

Perineum 

Raised, patch 

Erythematous, leukoplakia, pigmented 

Ulcerated 

Condylomatous 

Nodular 

1. DDx of vulvar dermatoses versus VIN ………… 

achieved primarily by 

2. Vulva lesions should be to determine 

histopathology….to direct for an appropriate Rx 

3. VIN is associated with 

and is a known precursor of vulvar SCC 

Herpes Vulvitis 

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Bartholin Duct Cyst 

Bartholin's Abscess 

Vaginal Wall Cyst 

(Gartner’s duct cyst) 

Epidermal inclusion cyst 

cyst of hair follicle (follicular cyst) 

Skene duct cyst 

Cyst of vulva 

lining 

wall 

Bartholin duct 

cyst 

Sq, transition, 

mucinous 

Bartholin gl. 

Mucinous vestibule 

cyst 

Mucinous , sq 

metaplasia 

No smooth 

musle 

Mesonephric 

like cyst 

Low cuboid, 

col. No ciliated 

Sm muscle 

beneath BM 

2 

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may express in 3 forms 

1. Fully expressed….as c. acuminata 

2. Minimally expressed….as koilocytes 

3. Latent….no morphological changes 

(detected only by molecular technique) 

Moist-- appear white 

frequently occur at multiple sites 

Parakeratosis 

papillomatosis 

hyperkeratosis 

Gross: Dry– appear brown 

Verrucous appearance 

Condyloma acuminata 

May be solitary, but more of multiple and coalesce 

May involve perineal, vulvar, perianal, vagina, and cervix 

Acanthosis 

Parakeratosis 

Basal cell hyperplasia 

koilocytes (perinuclear “halo”) 

freq seen in upper layer of epidermis 

koilocytosis (perinuclear “halo”) 

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Fibrovascular core, covered by sq epith. 

Paillomatosis 

Lack koilocytosis! 

Squamous papilloma 

Lichen sclerosus et atrophicus 

Clinical: 

• Whitened thinned epithelium 

• Symmetrical distribution 

• Labia minora shrinkage and agglutination in late stages. 

• Narrowed introitus or perianal stenosis (in children) 

• Occur in all ages grps, but common in postmenopause... 

• Unclear pathogenesis 

(genetic, autoimmunity, hormonal factors) 

• Insidious and progressive 

• Causes discomfort & predisposes to infection 

• Generally, not a precancerous condition 

BUT….a small proportion (about 1% to 4%) have been 

observed to develop carcinoma. 

1. Epithelial thinning/ hyperkeratosis 

2. Flattening rete ridges 

3. dermal edema and fibrosis 

Epithelial thinning with hyperkeratosis 

Hypertrophic vulvar dystrophy 

4. inflammatory cells 

Flattening of rete ridges 

Subepithelial or dermal edema and 

collagenous fibrous tissue change 

Chronic inflammatory cells in the areas 

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hyperkeratosis... 

thickened keratin layer 

(secondary lichenification) 

expanded papillary dermis. 

**Biopsy is indicated in all lesions…… 

thickened epithelium, increased mitotic activity in both basal & prickle cell layers 

even those that are not so suspicious 

variable leukocytic infiltration of the dermis... 

squamous hyperplasia 

(previously called hyperplastic dystrophy) 

Lymphocytic inflammatory reaction 

Sclerotic or edematous change of 

dermoepidermal junction 

may present as: 

ulcer 

nodule 

macule 

pedunculated mass 

discharge 

bleed 

pain 

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Vulvar Intraepithelial Neoplasia 

(VIN) 

An intraepithelial squamous neoplasm of the vulva. 

If multiple abnormal areas , then …….. 

multiple biopsies are required…….. 

to "map" all potential sites of vulvar pathology. 

Usually associated with high risk HPV infection, 

especially ill types 16 or 18. 

peak kincidence id ~ 20-35 yrs 

1/5 were assocd with SCC 

May follow, or be associated with cervical or vaginal 

neoplasia. 

A known precursor of vulvar squamous cell CA 

~ 3% of genital malignancies in women 

VIN: LESION COLOR (N=73) 

1. VIN and associated HPV infection (usually HPV type 16). 

2. The simplex (differentiated) type of VIN, not associated 

with HPV infection 

3. Lichen sclerosus with associated squamous hyperplasia 

4. Chronic granulomatous vulvar disease such as 

granuloma inguinale (rare in developed countries) 

Color Patients # % 

White 41 56.2 

Red 13 17.8 

Pigmented 12 16.4 

Unavailable 7 9.6 

Wilkinson EJ, World Health Organization, 2004 

Wilkinson EJ 

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VIN: type of lesion (N=73) 

Presentation Patients # % 

Multifocal l 57 78.1 

Unifocal 15 20.5 

Confluent 1 1.4 

VIN type SCC Type HPV Related 

Warty Condylomatous (Warty) Yes 

carcinoma 

Basaloid Basaloid carcinoma Yes 

Differentiated Keratinizing carcinoma No 

(Simplex type) 

Wilkinson EJ 

VIN 1 Mild dysplasia 

VIN 2 

Moderate dysplasia 

VIN 3 Severe dysplasia (8077/2) 

VIN 3 Carcinoma in situ (8072/2) 

* ICD-O, International Classification of Disease for Oncology 

Wilkinson EJ et al. Histological Typing of Female Genital Tract Tumors, in World Health Organization International Histological Classification of Tumours 

third Ed., 2004 

* 

VIN 1: abnormal epithelial cell involve lower 1/3 of the 

epithelium (maturation in the upper 2/3 of epithelium) 

VIN 2: abnormal epithelial cell involve lower 1/2 of the 

epithelium (maturation in the upper 1/2 of epithelium) 

VIN 3: abnormal epithelial cell involve most or all of the 

epithelium ( maturation present in the upper 1/3 of epithelium) 

Wilkinson EJ, World Health Organization, 2004 

VIN I 

Key points: 

Proliferation of basal layer 

Koilocytotic atypia 

* Enlarged pleomorphic nuclei 

* vacuolated cytoplasm 

-Disordered maturation 

* loss of polarity 

-Nuclear atypia 

* pleomorphism 

* coarse chromatin 

* irregular nuclear 

membrane 

* atypical MF 

VIN II 

• More proliferation 

• cytologic atypia in 

basal/parabasal 

layers 

• involving lower 1/2 

epithelium 

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Full thickness epith. 

replaced by abnormal 

basal and parabasal 

cells. 

VIN 3 

Oval nuclei with axis perpendicular to BM, except 

superficial layer where they are horizontal 

Bowenoid type 

VIN 3 

Basaloid type 

VIN 3 

VIN of differentiated 

(simplex) type 

Atypia is confined to basal 

& parabasal layers 

Squamous cell with maturation 

on epithelial-stromal junction 

suggestive of impending 

invasion 

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Cases should be classified as CA vulva when 

1 o site of the growth is in the vulva. 

Exclude 2 O tumor growth from other genital or 

extra- genital site 

Vulva CA VS CA vagina 

Malignant melanoma should be reported 

separately. 

A. Squamous cell carcinoma 

B. Adenocarcinoma 

C. Adenoid cystic carcinoma 

D. Adenosquamous carcinoma 

E. Transitional cell carcinoma 

F. Undifferentiated 

A. Embryonal rhabdomyosarcoma 

(sarcoma botryoides) 

B. Leiomyosarcoma 

C. Malignant fibrous histiocytoma 

D. Epithelioid sarcoma 

E. Aggressive angiomyxoma 

F. Dermatofibrosarcoma 

protuberans 

G. Epithelioid sarcoma 

H. Malignant rhabdoid tumor 

I. Malignant nerve sheath 

tumor 

J. Angiosarcoma 

K. Kaposi sarcoma 

L. Hemangiopericytoma 

M. Liposarcoma 

N. Alveolar soft part sarcoma 

O. Other sarcomas(Enzinger 

& Weiss or WHO) 

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A. Malignant melanoma 

B. Endodermal sinus tumor (yolk sac tumour) 

C. Neuroectodermal tumours (Merkel cell) 

D. Lymphomas 

E. Others 

Most epithelial malignant tumours (carcinomas) 

are fr. skin, mucosa or rarely bartholin gld., 

~ 3% of all female genital CA 

90% are SCC, the remainder are melanoma, 

basal cell carcinomas, or adenocarcinoma 

A. Invasive Squamous cell carcinoma 

1. Keratinizing 

2. Non-keratinizing 

3. Basaloid carcinoma 

HPV related 4. Verrucous Carcinoma 

5. Warty carcinoma [condylomatous] 

B. Basal cell carcinoma 

C. Adenocarcinoma 

S 

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C 

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• Uncommon variant of SCC, low malignant behavior 

• Very slow growing, although can grow very large, 

still carry an excellent prognosis. 

• Gross: may resemble condyloma acuminatum and 

present as a large fungating or cauliflower tumor 

mass. 

Exo- and endophytic 

tumor growth 

Papillomatosis (lack connective tissue core as seen in c.acuminata) 

hyperkeratosis 

undulating surface, 

pushing border, 

Tumor with pushing border, with acanthotic rete ridges extending 

deep into underlying tissue 

well differentiated SCC 

minimal cytologic atypia 

For recurrence: 

1. Stage, advanced 

2. Size > 2.5 cm 

3. Multifocal 

4. LVSI 

5. Assocd. VIN 2-3 

6. Margin involvement 

For survival: 

7. LN involvement 

8. Mode of treatmentt t 

9. Spray or finger-like pattern 

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Tumor nests& cords 

basal cell, showing 

peripheral palisading 

Malignant skin tumor, cells of basal layer of epidermis & adnexal structures. 

The College of American Pathologists (CAP) 

Small foci of 

sq.differentiation 

1. Depth of tumor invasion. 

2. Tumor thickness. 

3. Method of measurement…..depth th of invasion 

i 

& tumor thickness. 

4. Presence vascular space involvement 

5. Diameter of tumor, including the clinically 

measured diameter if available. 

Wilkinson EJ. Arch Path Lab Med 2000;124:51-6, 

A: Depth of invasion 

epithelium-stromal junction of 

Methods of 

the most superficial dermal 

papillae to the deepest 

invasion 

A 

B 

C 

B: measurement 

Tumor thickness 

Surface of the lesion to the 

deepest invasion 

of superficial 

C: Tumor thickness 

Paget disease 

Melanoma 

(when suface is keratinized) 

granular layer to the deepest 

invasion invasive CA 

ISSVD: Wilkinson EJ, Lynch PJ, Kneale B. J Reprod Med 31:973-4, 1986 

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* 1 st described in 1888, Crocker reported Paget 

disease of scrotum and penis, 2 o to bladder CA 

* Most commonly involves external genitalia, less 

common over perianus 

* Also reported in other areas of axilla, umbilicus, 

groins, eyelids, external ear canal. 

* Age: 45-91 yrs (median 67 yrs) 

* Associated carcinoma: 4-20% 

* Surgery: radical vulvectomy, partial vulvectomy, 

wide local l excision 

i 

* Recurrence rate 30-69% after surgery 

* Free margin : F.S., fluorescein-aided visualization 

(Controversy on significance of surgical margin) 

Wilkinson EJ & Brown HB, Human Pathology. 2003 

Brummer et al. Gynecol Oncol 2004;95:336-40. 

Molinie etal. Ann Dermatol Venereol 1993;120:522-7 

Lu et al. Zhonghua Fu Chan Ke Za Zhi 1999;34:156-8 

Misas et al. Obstet Gynecol 1991;77:156-9. 

Primary Paget disease: 

* as a 1 o intraepithelial neoplasm. 

* as an intraepithelial neoplasm with invasion. 

* as a manifestation of an underlying cutaneous, or vulvar ACA 

Secondary Paget disease: 

* 2 o to adjacent non-cutaneous ACA (e.g. anal or rectal ACA) 

* of urothelial origin (PUIN) (pagetoid urothelial intraepithelial neoplasia) 

PUIN as a manifestation of intraepithelial urothelial neoplasia (CIS) 

or invasive urothelial CA 

* of other origins 

Wilkinson EJ and Brown HB, Human Pathology. 2003 

1 o lesion (more common) 

* arise within epidermis & extend into 

contiguous epithelium of skin 

* arise from skin appendages (usually 

apocrine glands) & extend to overlying 

epidermis by epidermotropism. 

2 o lesion 

* non-cutaneous CA--- involves skin by direct 

extension or epidermotropic metastasis 

Wilkinson EJ and Brown HB, Human Pathology. 2003 

Paget disease in 

vulvectomy specimen 

Paget disease of vulva 

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Clinical: 

* Pruritic red, crusted, sharply demarcated, maplike area, 

* Occurring usually on the labia majora. 

* Possible palpable submucosal thickening or tumor 

BUT….tumor cells often extend into skin appendages and 

may extend beyond the confines of the grossly visible 

lesion----- prone to recurrence. 

Prognosis is poor if associated with 

invasive cancer!! 

Paget disease as an intraepidermal lesion, may persist for 

many years without invasion. 

Clear halo, containing mucopolysaccharide 

(+ PAS, alcian blue, or mucicarmine stains) 

finely granular cytoplasm 

Single or small nests of large tumor cells in epidermis 

Ultrastructure: Paget cells display apocrine, eccrine, & 

keratinocyte differentiation 

Presumably arise from primitive epithelial progenitor cells. 

pale cytoplasm 

(stain for mucin, PAS-D stain, CEA, EMA) 

1 o Paget dis. 2 o Paget dis. 

prominent nucleolus 

wide & deep surgical excision 

directed toward Rx of ass. CA 

large round to oval nuclei 

40X 

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DDx of vulvar intraepithelial Pagetoid cells 

• 1 o Paget Disease 

Usually requires IHC to distinguish 

• 2 o Paget disease 

• Vulva intraepithelial neoplasia 

• Superficial spreading melanoma 

• Pagetoid Spitz nevus 

• Sebaceous carcinoma 

• Merkel cell carcinoma 

• Clear cell papulosis (related to Toker cells) 

• Cutaneous T-cell lymphoma 

• Histiocytosis X 

• Langerhans’ cell microabscess 

• Benign mucinous metaplasia of vulva 

IHC findings of Paget disease 

Type CK-7 CK-20 GCDFP-15 CEA UP- III 

1 O skin + - + + (most) - 

1 O anorectal CA (+) + - + (>90%) - 

1 O urothelial CA + (+) - + (67%) + (50-60%) 

CK, cytokeratin; CEA, carcinoembryonic antigen; GCDFP, gross cystic disease fluid protein; 

UP, uroplakin 

Brown & Wilkinson. Hum Pathol 2002;33:545-8. 

Tumor of vagina 

• Epithelial tumor 

Tumor of vagina 

• Mesenchymal tumor 

• Mixed epithelial and mesenchymal tumor 

• Melanocytic tumor 

• Miscellaneous tumor 

Epithelial tumor 

• Squamous tumor : 

– squamous cell carcinoma : keratinizing, 

nonkeratinizing, basaloid, verrucous, warty 

– Squamous intraepithelial neoplasia : VAIN 

– Benign squamous lesions : Condyloma 

acuminata, squamous papilloma (vaginal 

micropapillomatosis), fibroepithelial polyp 


• Glandular tumor 

– Clear cell adenocarcinoma 

– Endometrioid adenocarcinoma 

Mucinous adenocarcinoma 

– Mucinous adenocarcinoma 

– Mesonephric adenocarcinoma 

– Malignant papilloma 

– Adenoma : tubular, tubulovillous, villous 

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• Other epithelial tumors 

– Adenosquamous carcinoma 

– Adenoid cystic carcinoma 

– Adenoid basal carcinoma 

– Carcinoid 

– Small cell carcinoma 

– Undifferentiated carcinoma 

Vaginal intraepithelial neoplasia (VAIN) 

• Premalignant lesion of the vainal squamous 

epithelium that can develop primary in the 

vagina or as an extension from the cervix 

• Histologically VAIN is defined in the same way 

as cervical intraepithelial neoplasia (CIN) 


• Much less common than CIN 

• Mean age is 50 years 

• Majority occur in prior hysterectomy or history of 

cervical or vulvar neoplasia 

• Increase incidence among young and 

immunosuppressed women 

• Associated with HPV infection (HPV type 16) 


• More commonly multifocal 

• Isolated lesion are mainly in the upper third of 

vagina and vaginal vault after hysterectomy 

• VAIN is asymptomatic and cannot be diagnosed 

by the naked eye 

• Detection is by mean of colposcopic biopsy 



• VAIN is always iodine-negative 

• Presence of punctuation on a sharply 

demarcated aceto-white area is the sinle 

most reliable feture suggestive of VAIN 

• Histopathology is the same as CIN 

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• Differential diagnosis 

– Atrophy 

– Squamous atypia 

– Transitional metaplasia 


• Prognosis 

– Low grade VAIN : 88% regress without treatment 

– High grade VAIN : 8% progress to invasive CA 

– Recurrent rate is 33% 

Mesenchymal tumor 

• Sarcoma botryoides 

• Leiomyosarcoma 

• Endometrioid stromal sarcoma, low grade 

• Undifferentiated vaginal sarcoma 

• Leiomyoma 

• Genital rhabdomyoma 

• Deep angiomyxoma 

• Postoperative spindle cell nodule 

Sarcoma botryoides 

• A malignant mesenchymal tuor composed 

of small round or oval to spindle shaped 

cells some of which show evidence of 

striated muscle differentiation 

• Embryonal rhabdomyosarcoma 


• Most common vaginal sarcoma 

• Occurs almost exclusively in children and infants 

< 5 years of age (mean 1.8 years) 

• Occuring in young adult, pregnancy, 

postmenopausal women were reported 

• Present as a vaginal mass with soft edematous 

polypoid nodules or grape-like nodules often 

protruding through the introitus 


• Most common vaginal sarcoma 

• Occurs almost exclusively in children and 

infants < 5 years of age (mean 1.8 years) 

• Occuring in young adult, pregnancy, 

postmenopausal women were reported 

• Present as a vaginal mass with soft 

edematous polypoid nodules or grape-like 

nodules often protruding through the 

introitus 

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Benign conditions 

Vaginal adenosis 

• Found in 1/3 asymptomatic girls or young women 

exposed to DES, CO2laser vaporization, tropical 5FU 

treatment of condyloma 

• Rare in postmenopausal age group 

• Upper 1/3 of vagina usually effect, middle 1/3 10%, 

lower1/3 2% 

• Adenosis rarely develop clear cell adenocarcinoma or 

vaginal intraepithelial neoplasia 

Adenosis 

Micro : 

• Benign type columnar 

epithelium replaces 

normal squamous 

epithelium or forms 

glands within superficial 

stroma 

• Endocervical or 

tuboendometrioid 

• Squamous metaplasia of 

glands may be missed 

diagnosis as squamous 

cell CA 

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Postoperative Spindle Cell Nodule(PSCN) 

• Reactive pseudosarcomatous spindle cell 

lesion 

• Develop shortly after operation on lower 

genitourinary tract 

• Detect in operative site 112 weeks after surgy 

• PSCN in upper vagina usually followed 

vaginal hysterectomy 

• PSCN in lower vagina or vulva usually 

followed episiotomy 

Postoperative Spindle Cell Nodule(PSCN) 

• Benign clinical 

• Rare recur 

• Soft polypoid mass

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Fibroepithelial polyp 

• Usually single , may be multiple 

• Sessile , pedunculated, botryoid appearance 

•

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Aggressive angiomyxoma 

• Differential diagnosis : 

– Angiomyofibroblastoma (superficial location, 

small size, absence of thick wall muscular 

vessels, ,p presence of PMNs) 

–Myxoma 

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Herpes Vulvitis

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