Cervical and Vaginal Cancer

Chap. 32 Cervical and Vaginal Cancer



November 25. 1997

1st year resident Sung Hee Oh MD





: preventable cancer

mean age - 52.2 years

bimodal - 35-39 years and 60-64 years

primary vaginal cancer

- only 1-2% of malignant neoplasms of the female genital tract



CERVICAL CANCER


1 . Symptoms



1) vaginal bleeding




  • most common symptom
  • postcoital bleeding
  • irregular or postmenopausal bleeding


2) advanced disease



  • malodorous vaginal discharge, weight loss, or obstructive uropathy



2 . Physical examination



1) supracalvicular and groin lymph nodes


2) pelvic examination




  • speculum - cervix is inspected for suspicious areas
  • rectal exam - establish cervical consistency and size

    parametrial extension of disease is best determined by

    the finding of nodularity beyond the cervix



3) cervical biopsy




    : colposcopy may be helpful

    diagnostic conization



3 . Pathology



1) Microinvasive cervical squamous carcinoma



  • Cervical conization is required to assess correctly the depth and the linear extent of
    involvement of microinvasion


  • Lesions the are < 3mm are classified as FIGO stage Ia1.

    Lesions that are >3-5mm or more in depth and <7mm in linear extent are classified as
    FIGOstage Ia2


  • The depth of invasion is significant for the development of pelvic lymph node metastasis and
    tumor recurrence (more than 3-5mm : 5-8%)


2) Invasive cervical cancer



a. Squamous cell carcinoma





  • invasive squamous cell carcinoma is the most common variety of invasive cancer

  • large cell keratinizing /large cell nonkeratinizing / small cell types

  • The category of small cell carcinoma includes poorly differentiated squamous cell carcinoma and small cell anaplastic carcinoma , resembling oat cell carcinoma of the lung

  • Patients with the large cell type of carcinoma , with or without keratinization , have a better prognosis than with the small cell variant




b. Adenocarcinomas



  • increasing number of cervical adenocarcinomas affecting young women in their twenties and thirties


  • In addition, squamous neoplasia, intraepithelial or invasive , also occurs in 30-50% of cervical adenocarcinomas


  • Adenocarcinoma may be detected by cervical sampling but less reliably so than squamous carcinomas


  • A definitive diagnosis may require cervical conization


  • Pure - quite heterogeneous

    wide range of cell types, growth patterns, and differentiation

    80%, endocervical type with mucin production

    endometrioid cells, clear cells, intestinal cells, or a mixture of more than
    one cell type


  • minimal deviation adenocarcinoma (adenoma malignum)

    extremly well- differentiated form of adenocarcinoma

    more recent studies have found a favorable prognosis if the disease is detected early



  • villoglandular papillary adenocarcinoma
    young women (pregnant or users of oral contraceptives)

    none of theses tumors has recurred after cervical conization or hysteretomy

    limited risk for spread beyond the uterus



  • mature adenosquamous carcinomas : identified on routine histologic sections


    In poorly differentiated or immature adenosquamous carcinomas

    mucicarmine and PAS - 30% of squamous carcinomas demonstrated mucin secretion
    when stained with mucicarimine

    mucin secretion have a higher incidence of pelvic lymph node metastases than
    squamous cell carcinomas without mucin secretion



  • glassy cell carcinoma

    poorly differentiated form of adenosquamous carcinoma

    the poor diagnosis of this tumor is linked to understanding and resistance to
    radiotherapy



  • adenoid basal carcinomas

    simulates the basal cell carcinoma of the skin

    peripheral palisading

    mitoses are rare

    tumor often extends deep into the cervical stroma



  • adenoid cystic carcinoma

    invade into the adjacent tissues and metastasize late, often 8-10years after the
    primary tumor has been removed
    directly to the lung



c. Sarcoma




  • embryonal rhabdomyosarcoma

    in chidren and young adults

    grape- like polypoid nodules , the botryoid sarcoma



d. Malignant melanoma




  • on rare occasions, de novo in this area
  • the depth of invasion into the cervical stroma



e. Metastatic cancer




  • involved in cancer of the endometrium and vagina


  • consequently the clinical classification is that of cervical neoplasia extending to the vagina, rather than vice versa


  • three modes, direct extension from the endometrium, submucosal involvement by lymph vascular extension and multifocal disease


  • carcinomas of the urinary bladder and colon


  • lymphoma, leukemia, and carcinoma of the breast, stomach, and kidney is usually part of the systemic spread



f. Small cell carcinoma



  • at the time of diagnosis , it is usually disseminated with bone, brain, liver, and bone marrow being the most common sites of metastases




4. Colposcopy of the invasive lesion



: suggest invasion

abnormal blood vessels

irregular surface contour with loss of surface epithelium

color tone change

colposcopically directed biopsies may permit the diagnosis of frank invasion and thus avoid the
need for diagnostic cone biopsy, allowing treatment to be administered without delay



1) Abnormal blood vessels


: looped, branching, or reticular



  1. looped vessels are the most common and arise from the punctation and mosaic vessels
    present in cervical intraepithelial neoplasia (CIN)



  2. the abnormal branching blood vessels




    • obtuse or right angles
    • enlarging after branching



  3. abnormal reticular vessels




    • the terminal capillaries of the cervical epithelium
    • in a postmenopausal woman with atrophic epithelium
    • the surface is again eroded , and the capillary network is exposed ,these vessels are very
      fine, short, and composed of small commas without an organized pattern
    • not specific for invasive cancer, atrophic cervicitis may also have this apperance





2) Irregular surface contour




  • papillary characteristic of the lesion
  • with a human papillovirus papillary growth on the cervix,

    biopsies should be performed on all papillary cervical growths



3) Color tone change




  • as a result of the increasing vascularity, surface epithelial necrosis

    , production of keratin

    , yellow-orange



    * Adenocarcinoma


    : not have a specific colposcopic appearance

    endocervical curettage is required as part of the colposcopic examination



5 . Staging



1) Clinical staging



: When there is doubt concerning the stage to which a cancer should be allocated , selection of the earlier stage is mandatory


After a clinical stage is assigned and treatment has been initiated, the stage must not be changes because of subsequent findings by either extended clinical staging or surgical staging



* extended clinical staging



lymphangiography, CT,USG,and MRI-be used in planning therapy



2) Patterns of spread



    a. direct invasion

    b. lymphatic metastasis

    c. blood-born metastasis

    d. intraperitoneal implantation



6. Treatment



: surgery, radiotherapy


(surgery alone is limited to patients with stage I and II a disease)


In general, radical hysterectomy is reserved for woman who are in good physical condition



1) Surgical therapy



  1. staging



    • stage Ia - microinvasive Carcinoma



      A microinvasive lesion is one in which neoplastic epithelium invades the stroma to
      a depth of <3mm beneath the basement membrane and in which lymphatic or blood
      vascular invlovement is not demonstrated." The purpose of defining microinvasionis
      to identify a group of patients who are not at risk of lymph node metastasis or
      recurrence and who therefore may be treated with less than radical therapy.



      Diagnosis must be based on a cone biopsy of the cervix

      pathologic condition be described in terms

      depth of invasion/width and beneath of the invasive area/presence or absence of
      lymphatic vascular space invasion



      Stage Ia1-<3mm invasion


      < 1% incidence of pelvic node metastasis

      extrafascial hysterectomy without node dissection

      therapeutic conization appears to be adequate therapy for these patients if
      childbearing capability is desired

      surgical margins must be free of disease

      if there is lymph vascular space invasion, an alternative is an pelvic node
      dissection with a typeI (extrafascial) or II (modified radical) hysterectomy



      Stage Ia2->3-5mm invasion


      3. 8% incidence of pelvic node metastasis

      pelvic node dissection is necessary for these lesions

      modified radical hysterectomy (type II)



    • stageIb /II a invasive cancer


      radical hysterectomy, pelvic lymphadenectomy, and para aortic lymph node evaluation




  2. Types of hysterectomy




    • Modified radical hysterectomy (Type II)

      medial one-half of the cardinal and uterosacral ligaments


    • Radical hysterectomy (Type III)

      The operation includes a pelvic lymph node dissection, along with removal of most of the
      uterosacral and cardinal ligaments and the upper one-third of the vagina


    • Extended radical hysterectomy (Type IV)

      periureteral tissue, superior vesicle artery, and up to three-fourths of the vagina are
      removed


    • Partial exenteration (TypeV)

      portions of the distal ureter and bladder are resected



      figure 32.8 the pelvic ligaments and spaces



      * Modified radical hysterectomy


    • The uterine artery is transected at the level of the ureter, thus preserving the
      ureteral brance to the ureter


    • The cardinal ligament is not divided near the sidewall but instead is divided
      at approximately its midprotion near the ureteral dissection


    • The anterior vesicouterine ligment is divided, but the posterior vesicouterine
      ligament is conserved


    • A smaller margin of vagina is removed



  3. Complications of radical hysterectomy




    • Acute complications

      blood loss (average 0.8 L)

      ureterovaginal fistula (1-2%)

      vesicovaginal fistula (<1%)

      pulmonary embolus (1-2%)

      small-bowel obstruction (1%)

      febrile morbidity (25-50%)

      most often pulmonary (10%)

      pelvic cellulitis (7%)

      urinary tract infection (6%)


    • Subacute complications

      bladder dysfunction

      important to maintain adequate bladder drainage during this time to prevent
      overdistention (with a suprapubic catheter)

      cystometrography may be performed 3 to 4 weeks postoperatively

      For use of the cathter to be discontinued, the patient must be able to sense
      the fullness of the bladder, initiate voiding , and void with a residual
      urine level of <75ml.


      Lymphocyst

      fewer than 5% of patients

      cause is uncertain

      adequate drainage of the pelvis after radical hysterectomy may be an
      important step in prevention

      simple aspiration of the lymphocyst is generally not curative
      ,but percutaneous catheters with chronic drainage may allow healing

      if this treatment is unsuccessful, operative intervention with excision of a
      portion of the lymphocyst wall and placement of either large bowel
      or omentum into the lymphocyst


    • Chronic complications

      Bladder hypotonia (or atony)

      3%

      result of bladder denervation

      voiding every 4-6 hours, increasing intra-abdominal pressure with the
      Crede's maneuver, and intermittent self-catheterization may be used to
      manage the hypotonic bladder


      Ureteral stricture

      uncommon

      lymphocyst,radiation therapy,ureteral stenting,recurrent carcinoma



  4. results of surgical therapy





    • lymph nodes

      negative : 85-90% 5 year survival rate

      positive : 20 to 74%

      common iliac - 25% (5 yr survival rate)

      only the pelvic lymph nodes-65%

      bilateral positive pelvic- worse prognosis (22-40% survival rate)

      unilateral - 59-70%

      more than three positive pelvic lymph nodes- 68% recurrence rate

      few - 30-50%

      tumor emboli - 82.5% 5 yr survival rate

      microinvasive - 62.1%

      macroscopic disease - 54%



    • lesion size

      independent predictor of survival

      smaller than 2cm have a survival rate of approximately 90%

      larger than 2cm have a 60% survival rate

      larger than 4cm , the survival rate drops to 40%



    • depth of invasion

      less than 1cm have a 5 yr survival rate around 90%

      more than 1cm ,63-78%


      • parametrial spread

        5-yr survival rate 69%

        negative (95%)


      • lymph vascular space involvement

        50-70%,



  5. postoperative radiotherapy



    • with high-risk : metastasis to pelvic lymph nodes

      invasion of paracervical tissue

      deep cervival invasion

      positive surgical margins


    • from retrospective studies, it appears that postoperative radiation therapy for positive
      pelvic nodes can decrease pelvic recurrence but does not improve 5yr actuarial
      survival




  6. neoadjuvant chemotherapy



    : use of chemotherapy to shrink the tumor before radical hysterectomy or radiotherapy




    • 22-44% complete response rate, decrease the number of positive pelvic lymph nodes,
      and improve the 2- and 3- year disease - free survival rates, particularly in
      patients with stage I and II disease


    • Kim et al, cisplatin, vinblastine and bleomycin

      (54patients with stage I and II a tumors larger than 4cm)

      complete response rate of 44%

      partial response rate of 50%

      only three patients - recurred

      94% disease - free survival with a minimum of 2 years follow-up


    • Panici et al,cisplatin, bleomycin, and methotrexate

      (75patients with stage I ,II and III , larger than 4 cm)

      100%,81% and 66% (3year disease - free survival rate)

      initial large tumor size and parametrial infiltration significantly correlated with
      a lower response to neoadjuvant therapy

      recurrence was significantly correlated with FIGO stage, parametrial infiltration,
      and residual cervical tumor