Vulva pathology

VULVA PATHOLOGY

Vulva or external genitalia consists of:

• 
  labia majora
  
• 
  labia minora
  
• 
  clitoris
  
• 
  vestibule
  
• 
  hymen
  
• 
  vestibular bulbs
  
• 
  mons veneris
  
• 
  urethral meatus
  
• 
  vulvovaginal glands
  
• 
  periurethral gland ducts
  
• 
  skin-with hair follicles and sweat and sebaceous glands.
  

Clasification of benign conditions of the vulva:

1. 
   skin conditions
   
2. 
   pigmented lesions
   
3. 
   tumors and cysts
   
4. 
   ulcers
   
5. 
   dystrophies
   

1. Skin conditions

1. 
   sexually transmistted diseases
   
   1. 
      Genital herpes (herpes simplex virus 2):
      

• 
  is a recurrent infection
  
• 
  the onset of disease appears after between 1-45 days after exposure to the virus
  

Simptoms: bilateral lessions, painful occur on the external genitalia, accompanied by bilateral tender lymphadenopathy of the inghinal or femoral regions.

Differential diagnostic: syphilis and gonorrehea

Paraclinical examinations:

• 
  culture of the ulcers and vesicules, of the urethra, cervix and anus (virus isolation by tissue culture)
  
• 
  serologic tests for syphilis
  
• 
  cytological methods to identify changes in cells produced by HSV.
  

Treatament:

Acyclovir available in three formes:

• 
  topical application every 4 hours
  
• 
  intravenous acyclovir – for disseminated, herpes infection (pharyngits, hepatitis, aseptic meningitis, autonomic nervous system disfunction)
  
• 
  oral Acyclovir for reccurent disease
  

1. 
   Lymphogranuloma venerum:
   

• 
  Chlamydia – especially C trachomatis
  
• 
  It is a sexually trans mitted disease
  
• 
  Clinical examination:
  
  • 
    Papules, pustules or small ulcers – after a few days after intercourse
    
  • 
    Suppurative inguinal adenitis with subsequent necrosis and ulcerations
    
  • 
    Lymphatic extension may involve the rectum, the lower colon, and may produce strictures of the urethea and rectum, eventual incontinence
    

Diagnosis: complement fixation test and Frei test.

Treatment:

• 
  local cleansing and soothing measures
  
• 
  suppurating lymph nodes mist be aspirated and never incised
  
• 
  Tetracycline and Doxicyline 3-4weeks
  
• 
  Sometimes is necessary vulvectomy for severe deformity or colostomy for rectal stricture
  

CHANCROID (SOFT CHANCRE)

• 
  haemophilus dycreyi
  
• 
  lesion: painful papule or ulcer
  
• 
  diagnosis: the culture on blood agar plates
  

Treatment: erythromycin 500mg orally four tims daily for 7 days, or 250mg of ceftriaxone intramuscularly once.

GRANULOMA INGUINALE

• 
  etilogic agent – CALYMMATOBACTERIUM GRANULOMATIS or DONOVANIA GRANULOMATIS
  
• 
  small papular lesion on the labia minor or groin, later becoming serpiginous with pseudobubo or manifesting subcutaneous inghinal granulomas
  
• 
  treatment:
  
  • 
    tetracycline 1g/dailly 10 days to 14 days
    
  • 
    sometimes in late stage manifestation with important edema it is nesessary a vulvectomy
    

CONDYLOMATA ACUMINATA

• 
  the etiologic agent is hpv (human papilovirus types 6, 16, 18)
  
• 
  exophytic growths that appear as papillary lesions
  
• 
  the lesions may be solitary; may occur in clusters or into a large cauliflower-like masses
  
• 
  the location can be: or the labia, on the perineum, on the vagina or even or the cervix and in the perineal area.
  

Treatment: topical application of 25% podophyllin in tincture of benzoin, freezing, excision, laser and desiccation

The HPV infection is a risk factor for cervical carcinoma.

TRICOMONIASIS and candidia see cervical infection.

OTHER SKIN INFECTIONS

Pyoderma (impetigo):

• 
  the agent is staphylococcus or β hemolytic streptococcus (or both)
  
• 
  thin-walled vesicles that rupture, leaving a reddned weeping spot that becomes crusted occur and exudes pus
  

Folliculitis:

• 
  infection of the hair follicles and nearby sebaceous glands
  
• 
  there is a papule which is trasformed in a pustule
  
• 
  complications: cellulitis, lymphangitis or both, accompanied by fever and chills
  

Erysipelas:

• 
  is a variant of streptococcal infection
  
• 
  there are severe symptoms like headache, fever, chills
  
• 
  the lesion has a sharp border that is middly indurated
  

The treatment for all these other skin infections is penicillin or erytromycin until the results of the culturies of free pus are obtained

• 
  serologic tests for syphillis must be done
  
• 
  the complication of streptococcal infection can be the glomerulonephritis
  

Hidradenitis suppurativa:

• 
  is an infection of sweat glands
  
• 
  the etiology: staphylococcus, streptococcus, E.colli
  
• 
  the infection involves only the apocrine glands and affects mainly labia majora intercrural folds, occasionally the mons and extremely rarely the clitoris and labia minora
  
• 
  a secretory and a suppurative phase way be exhibited simultaneously drainage and wide surgical excision
  

Atrohic vulvitis and simple kraurosis

• 
  symptoms: vulvar burning, itching dyspareunia ± bleeding
  
• 
  appear in menopause
  
• 
  the cause – estrogen deficiency
  
• 
  labia majora is flatten as the result of loss of subcutaneous fat
  
• 
  the mons pubis is less prominent
  
• 
  the adjacent skin is thin and shiny
  
• 
  the vaginal orifice is narrow and stenotic and there is some vaginal dischange (a thin watery dischage)
  
• 
  Papanicolau test is necesarry in order to prevent a cervical neoplasia
  
• 
  Treatment; estrogen therapy:
  
  • 
    Local application of estrogenic creams colpotrophine;ovestin=ointment
    
  • 
    Oral estrogens: ovestin tb 2mg (estriol); premarin: 0,625mg or 1,25mg
    
  • 
    Estrogens associated with progesteron: Premella 2,5mg or 5mg; Trisequens
    

Simple kraurosis:

• 
  is a primary sclerosing atrophy limited to the labia minora, vestibule, urethra and clitoris
  
• 
  labia majora, perineum and perineal regions are not usually involved
  
• 
  the skin may be red with isolated patches of dark red or dull purple (krauoris rouge) in early stage
  
• 
  the skin is yellow pale with obliterated labial folds, atrophic mons veneris; the vaginal orifice is narrow and admits the index finger with deficulty
  

Histologically - hyperkeratosis (exces of keratin above the epithelium)

- it is not a pre-malignant disease

WIHITE LESIONS OF THE VULVA:

• 
  are the result of processes of depigmentation with loss or destruction of the melanocyte`s ability to manufacture mellanin, hyperkeratosis or sclerosis of vessels that nourish skin.
  

The classification of lessions after the International Society for the Study of Vulvar Disease estabilithed in 1975:

1. 
   Hiperplastic dystrophy:
   

• 
  without atypia
  
• 
  with atypia
  

2. 
   Lichen sclerosus
   
3. 
   Mixed dystrophy:
   

• 
  without atypia
  
• 
  with atypia
  

The classification of atypia is:

VIN I: (vulvar intraepithelial neoplastia) = mild dysplasia

VIN II: moderate dysplasia

VIN III: severe dysplasia = carcinoma in situ

1. 
   Hyperplasitic dystrophy includes:
   

• 
  hypertrophic vulvitis
  
• 
  lichen simplex chronicus
  
• 
  neurodermatitis
  

Microscopic aspect:

• 
  hiperkeratosis
  
• 
  dermal inflammation
  
• 
  elongation of rete pegs
  

The biopsy must assess the presence or absence of any atypia

Treatment:

• 
  topical corticosteroids
  
• 
  boric acid preparations for intense itch
  
• 
  if is necessary the biopsy must be repeated if de lesion reappears
  

2. 
   Lichen sclerosus:
   

• 
  age: both young and old people
  
• 
  neck, trunk, axilla ald extremities can be involued, or the lesion may be present primarily on the vulva
  
• 
  the general skin background is pale, peppered with whitish papular – appearing areas over the atrophic background
  

Histologically:

• 
  thin epithelium, associated with hyperkeratosis
  
• 
  loss of rete ridges
  
• 
  a collagenized subepithelial zone
  
• 
  inflamatory cells
  
• 
  there is a familly – history of the disease – there is a mother – daughter expression of a characteristic HLA pattern
  

Treatament:

• 
  aplication of 2% testosterone preparation in lanoline base daily until the symptoms are under control
  
• 
  if itching and burning persist – intermittent use of corticosteroid cream is helpful
  
• 
  vulvectomy with or without grafting cannot be expected to eradicate the process.
  

3. Mixed dystrophy

• 
  definition: presence of both lichen sclerosus and hyperplastic dystrophy
  
• 
  multiple biopsies are necessary in order to rule out atypia
  
• 
  treatment: aggressive topical therapy with alternating testoterone and corticosteroids
  

Carcinoma in situ – intraepithelial neoplastia:

• 
  the loss of epithelial arhitecture, not including keratinized or parakeratoyic layers
  
• 
  lesions may be white, red or pigmented
  
• 
  unifocal or multifocal
  
• 
  discrete or coalesced
  
• 
  the relationship to invazive cancer is not strong
  
• 
  the interval between the peak ages for carcinoma in situ of the vulva and invasive carcinoma is greater than that for cervical cancer.
  

DRY SCALY DERMATOSES

LICHEN PLANUS

• 
  is an inflamatory dermatosis
  
• 
  the etiology is unknown
  
• 
  clinical: multiple, small polygonal papules that have a violaceous color and are covered with an umbilicated horny film
  
• 
  the vulvar lesions are together with other lesions on the body: (wirists, ankles, inner thighs and oral mucosa)
  
• 
  there is some relation to an autoimmune cell-mediated response (pacients whe have had bone marrow transplants with graft-vs-host reaction)
  
• 
  diagnosis – the biopsy
  
• 
  vulvovaginal lesions are often refractory to the treatament with steroides
  

Psoriasis

• 
  inflamatory dermatosis of unknown origin
  
• 
  there are dry, patches of varions sizes covered by silvery white or graysh white scales
  
• 
  the lesions are present on the vulva, the scalp, nails, the extensor surface of the limbs, and the sacral area
  
• 
  diagnostis: clinical and biopsy
  
• 
  treatament: topical use of corticosteroides
  

SEBORRHEIC DERMATITIS

• 
  Is a red rash appearing in areas of skin where there is a high concentration of sebeaceous glands
  
• 
  Lesions can ivolve the scalp (“dandruff” term is used), areas behind the ears, between the scapula, crural folds, perianal area, labia majora, mons and, intertriginous areas
  
• 
  If vulva is affected there is severe itching, with the secondary excoration and infection
  
• 
  Treatment:
  
  • 
    Tranquilizers
    
  • 
    Good hygiene
    
  • 
    Topical steroid
    
  • 
    Infection treatment with antibiotics if neccessary
    

NEURODERMATITIS

• 
  includes atopic dermatitis and lichen simplex chronicus
  
• 
  there is inflamation, excoriation, lichenifications, hyperpigmentation or lack of pigmentation, hyperkeratosis – confusion with other dystrophies
  
• 
  treatment:
  
  • 
    tranquilizers
    
  • 
    antihistamines
    
  • 
    sedatives
    
  • 
    of 1% triamcinolon ointment
    

BENIGN TUMORS OF THE VULVA

(NEVUS VERRUCOSUS)

• 
  papiloma – is a dermal papilloma which may occur on the vulva
  
• 
  it may be single or multiple
  
• 
  histologically: hyperkeratosis with acanthosis and elongation of the rete ridges
  
• 
  treatment = excision
  

LIPOMA

• 
  a benign tumor that arrises from the fatty tissue of the labia majora or mons veneris
  
• 
  is painless
  
• 
  the size is 10–12 cm to the gigantic zize (in this situation the mass acquires a pedicle and hangs from the groin or vulva as a pendulum)
  
• 
  histologically: normal fat tissue with a connective tissue framework and capsule: liposarcoma is extremely rare
  
• 
  treatment: excision
  

FIBROMA

• 
  a firm nodule on the labia majora which can grow and develop a pedicle
  
• 
  the histological aspect is of any dermatofibroma
  
• 
  treatment=excision
  

HIDRADENOMA

• 
  is a beningn, slow – growing sweat gland tumor, whose histology similates that of an adenocarcinoma
  
• 
  treatment: excision and biopsy
  

MALIGNANT NEOPLASMS

• 
  carcinoma of the labia majora, minora and vestibule – more common
  
• 
  rare: clitoris, adenocarcinoma of Bartholin`s gland, adenocarcinoma of sweat glands, sarcomas, malignant melanomas, teratomas and Paget`s disease
  

CARCINOMA OF THE VULVA

(squamous cells)

STAGING

Stage 0 – carcinoma in situ – VIN₃ nonivasive Paget`s disease

Stage I – tumor confined to the vulva:

T₁N₀M₀ 2cm or less in largest diametre and no suspicious groin nodes

T₁N₁M₀

Stage II – tumor confined to the vulva:

T₂N₀M₀ more than 2 cm in diameter, and no suspicious groin nodes

T₂N₁M₀

Stage III – tumor of any suze with:

T₃N₀M₀ a) adjacent spread to the urethra and/or vagina, the perineum and anus

T₃N₁M₀

T₃N₂M₀

T₁- T₂ N₂M₀ b) clinically suspicious lymph nodes in either groin

Stage IV

T_nN_xM₀ tumor of any size

T_xN₃M₀ a) infiltrating the bladder mucosa or rectal mucosa or both,

T_xN_xM_1a including the upper part of the uretheal mucosa

T_xN_xM_1b b) fixed to the bone

c) other distant metastases

T – primary tumor (see the text)

N- regional lymph nodes:

• 
  N₀ – no nodes palpable
  
• 
  N₁ – nodes palpable in either groin, not enlarged, mobile (not clinically suspicious for neoplasm)
  
• 
  N₂ – nodes palpable in either or both groins enlarged, firm and mobile (clinically suspicious for neoplasm)
  
• 
  N₃ – fixed or ulcerated nodes
  

M – distant metastases:

• 
  M₀ – no clinical metastates
  
• 
  M_1a – palpable deep pelvic lymph nodes
  
• 
  M_1b – other distant metastases
  

Routes of spread:

• 
  direct extension – which involves vagina, urethra, perineum
  
• 
  lymphatic embolization of regional lymph nodes:
  
  • 
    ingninal-femoral nodes (Cloquet node)
    
  • 
    pelvic nodes – external iliac group
    
• 
  hematogenous spread to distant sites, including the lungs, liver and bones
  

Treatment:

Surgery: radical vulvectomy with bilateral lymphadenectomy ingninal-femoral in early stages; pelvic lymphadenectomy is reseved for positive groin nodes, unless the primary tumor involves the clitoris or Bartholin gland.

Complications of radical vulvectomy:

- immediate:

1. 
   Schock – the pacient is old, the operation is long
   
2. 
   Thrombosis and pulmonary embolism (risk for elderly pacients in pelvic surgery)
   

- later:

• 
  chronic oedema is likely if there has been any thrombosis
  
• 
  coitus should be possible after the operation, but removal of the clitoris ends all erotic sensation: the patients must be aware about this risk before the operation.
  

Prognosis after radical vulvectomy:

• 
  pacient`s age (elderly people)
  
• 
  GRADDING
  
  • 
    G1 – well differentiated
    
  • 
    G2 – moderate differentiated
    
  • 
    G3 – nondiferentiated
    
• 
  lymphatic nodes:
  
  • 
    50% of patients the inguino-femoral nodes are involved
    
  • 
    15% lateral pelvic nodes
    
  • 
    5 year survival rate:
    
    • 
      40% when the superficial nodes are involved
      
    • 
      20% when the pelvic nodes are involved
      

Radiotherapy:

• 
  it is not a treatment of choise
  
• 
  is used for old patients and for relatively young patients (fifty years old) like an alternative to the vulvectomy operation (a mutilating one)
  
• 
  patients with 2 or more positive groin nodes
  
• 
  radiation therapy consists of 4500-5000 cGy to the midplane of the pelvis at a rate of 180-200cGy per day
  

Indications of radiotherapy:

1. 
   properatively in patients with advanced disease
   
2. 
   postoperatively, to treat the pelvic nodes and groin of patients with two or more positive groin nodes
   
3. 
   postoperatively to help prevent local recurrences
   
4. 
   as primary therapy for patient with small primary tumors in young and middle-aged women, in order to ovoid a vulvectomy.
   

CHEMOTAERAPY:

Cisplatin and 5 fluorouracil, preoperatively associated with radioterapy for pacients with advanced vulvar cancer who would otherwise require pelvic exenteration

PAGET`S DISEASE of the vulva

Is an intraepithelial carcinoma which may progress to invasive carcinoma and lymph nodes metastasis.

Treatment: excision and for invasive disease radical vulvectomy and bilateral lymphadenectomy.

Paget`s cells: are large, cells, lacking prickles and are surrounded by clear spaces, cytoplasm is light and the nuclei are large, round and pale.