Vulva
Protocol applies to carcinomas and to malignant melanomas of the vulva.
Procedures:
• Cytology
• Incisional Biopsy
• Excisional Biopsy
• Vulvectomy (with or without removal of other organs and tissues)

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.
It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with the document. Where a physician chooses to deviate from the protocol based on the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.
The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.

I. Cytologic material back Top Main Page

A. CLINICAL INFORMATION

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (e.g. previous therapy, previous tumors or operations of possible relevance, previous abnormal cytology)

b. Relevant findings (eg. appearance of lesion, laboratory data)

c. Clinical diagnosis

d. Procedure

e. Type(s) or site(s) of specimen(s):

(1) scraping of vulvar vestibule, lesion or tumor

(2) vesicle contents and scraping of vesicle base

(3) imprint of lesion

(4) fine needle aspiration

B. MACROSCOPIC EXAMINATION

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Number of slides received, if appropriate

c. Quantity and appearance of fluid specimen, if appropriate

d. Other (e.g. cytologic preparation from tissue)

e. Results of intraprocedural consultation

2. Material submitted for microscopic evaluation (e.g. smear, cytocentrifuge, touch or filter preparation; cell block)

3. Special studies (specify) (e.g. flow cytometry, immunocytochemistry)

C. MICROSCOPIC EVALUATION (Note A)

1. Adequacy of specimen (if unsatisfactory for evaluation, specify reason)

2. Tumor, if present

a. Histologic type, if possible (Note B)

b. Other features

3. Additional pathologic findings, if present

4. Results/status of special studies

5. Comments

a. Correlation with intraprocedural consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

II. Vulvar biopsy, incisional or excisional back Top Main Page

A. CLINICAL INFORMATION

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (e.g. previous therapy, previous tumors or operations of possible relevance, previous abnormal cytology)

b. Relevant findings (e.g. radiologic studies, laboratory data)

c. Clinical diagnosis

d. Procedure

(1) biopsy with cervical biopsy device

(2) punch biopsy, shave biopsy

(3) incisional biopsy

(4) excisional biopsy

e. Operative findings

f. Anatomic site(s) of specimen(s)

(1) vestibule, periurethral

(2) perineal body

(3) perineum

(4) labium minus

(5) labium majus

(6) clitoris

(7) frenulum

(8) prepuce

(9) mons

(10) other

g. Location(s) of specimen(s) (e.g. right or left; posterior or anterior)

h. Orientation of specimen(s), if necessary

B. MACROSCOPIC EXAMINATION

1. Specimen

a. Unfixed/fixed (specify fixative)

b. Size

(1) three dimensions if single or multiple and separately designated

(2) number, aggregate dimensions and size range, if multiple and not separately designated

c. Descriptive features

d. Orientation, if designated

e. Results of intraoperative consultation

2. Tumor, if present

a. Size (three dimensions including depth)

b. Descriptive features

3. Additional pathologic findings, if present

4. Resection margins if pertinent

5. Other tissue(s) present

a. Lesion(s), if present

(1) descriptive features

(2) location

(3) size

b. Margin(s) (proximity of lesions to margins, if pertinent)

6. Specimens submitted for microscopic evaluation

7. Special studies (specify) (e.g. flow cytometry, immunohistochemistry, HPV typing)

C. MICROSCOPIC EVALUATION

1. Tumor

a. Histologic type (Note B)

b. Histologic grade

c. Extent (measure if appropriate)

(1) site(s) of involvement

(2) depth of invasion (Note C)

(3) thickness (Note D)

(4) pagetoid spread

d. Type of invasion (e.g. broad-front, tentacular (finger-like), mixed, indeterminate) (Note E)

e. Lymphatic/blood vessel invasion (Note F)

f. Other features of possible prognostic or therapeutic significance

2. Findings at apparent site of prior tumor, if no tumor present

3. Resection margins if applicable and interpretable (if not interpretable, specify reason)

4. Additional pathologic findings, if present and relation to tumor, if pertinent

a. Other tumors (determine if metastatic or separate primary if possible)

b. Precancerous lesions (e.g. dysplasia/VIN [vulvar intraepithelial neoplasia])

c. Squamous cell hyperplasia

d. Lichen sclerosus

e. Condyloma acuminatum

f. Nevus

g. Other

5. Results/status of special studies (specify)

6. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information, as appropriate

III. Therapeutic local excision or vulvectomy back Top Main Page

with or without lymph node dissection and resection of adjacent tissues or organs; separate lymph node dissection

A. CLINICAL INFORMATION

1. Patient identification

a. Name

b. Identification number

c. Age (birth date)

2. Responsible physician(s)

3. Date of procedure

4. Other clinical information

a. Relevant history (e.g. previous therapy, previous tumors or operations of possible relevance, previous abnormal cytology)

b. Relevant findings (eg. radiologic studies, laboratory data)

c. Clinical diagnosis

d. Procedure (Note G) (specify, depth of excision, and dimensions of the excision in the vertical and horizontal axis)

e. Operative findings

f. Anatomic site(s) of specimen(s)

(1) vestibule, periurethral

(2) perineal body

(3) perineum

(4) labium minus

(5) labium majus

(6) clitoris

(7) frenulum

(8) prepuce

(9) mons

(10) other

g. Location(s) of specimen(s) (e.g. right or left; posterior or anterior)

h. Orientation of specimens, if necessary

B. MACROSCOPIC EXAMINATION

1. Specimen

a. Organs/tissues received (specify)

b. Unfixed/fixed (specify type)

c. Number of pieces

d. Dimensions (measure attached tissues individually)

e. Orientation of specimen if indicated by surgeon

f. Results of intraoperative consultation

2. Vulva

a. Tumor

(1) location

(2) size (three dimensions including depth)

(3) descriptive features (ulcerative, nodular, exophytic, verrucoid, other)

(4) extent (e.g., urethra, vagina, anus, etc) (Note H)(5) distances from margins, as appropriate

b. Margins (ink as appropriate)

c. Findings at apparent site of prior tumor, if no tumor present

d. Additional pathologic findings

(1) other tumors

i. determine if possible whether metastatic or separate primary tumors

ii. describe as for major tumor

(2) precancerous lesions (e.g. dysplasia / VIN [vulvar intraepithelial neoplasia])

(3) squamous cell hyperplasia

(4) lichen sclerosus

(5) condyloma acuminatum

(6) nevus

(7) other

e. Lymph nodes

(1) location

(2) number

(3) size

(4) tumor, if discernable

i. size

ii. descriptive features

f. Lymph nodes submitted separately

(1) location (as specified by surgeon)

i. inguinal-femoral (specify right, left, or both)

ii. pelvic (specify right, left, or both)

iii. other, specify

(2) number

(3) size

(4) tumor, if discernable

i. size

ii. descriptive features

g. Other tissue(s) (e.g. urethra, urethra and bladder, vagina, anus and rectum, symphysis pubis, other)

(1) description

(2) tumor, if present

i. location

ii. extent

iii. relation to vulvar tumor

(3) resection margins

(4) additional pathologic findings, if present

3. Specimens submitted for microscopic evaluation (Note I)

4. Special studies (specify) (e.g. flow cytometry, immunohistochemistry, HPV typing)

C. MICROSCOPIC EVALUATION

1. Tumor

a. Histologic type (Note B)

b. Histologic grade

c. Extent (Note H)

(1)measure if appropriate (greatest diameter of surface of tumor)

(2) anatomic site(s) of involvement

(3) depth of invasion (Note C)

(4) thickness (Note D)

(5) pagetoid spread

d. Type of invasion (e.g., pushing border; infiltrating border; mixed; indeterminate) (Note E)

e. Lymphatic/blood vessel invasion (Note F)

2. Other features of possible prognostic or therapeutic significance

a. Other tumors (determine if metastatic or separate primary if possible)

b. Precancerous lesions

(1) dysplasia/vulvar intraepithelial neoplasia[VIN]

(2) junctional nevus

c. Related benign lesions

(1) squamous cell hyperplasia

(2) lichen sclerosus

(3) condyloma acuminatum

3. Findings at apparent site of primary tumor, if no tumor present

4. Resection margins

5. Lymph nodes

a. Number at each designated site (Note H)

b. Number involved by tumor at each designated site

c. Presence or absence of extranodal extension (Note J)

6. Other organs and tissues

a. Tumor, if present

(1) location

(2) size

(3) extent

(4) relation to vulvar tumor

b. Resection margins, if applicable

c. Additional pathologic findings, if present

7. Results/status of special studies (specify)

8. Comments

a. Correlation with intraoperative consultation, as appropriate

b. Correlation with other specimens, as appropriate

c. Correlation with clinical information as appropriate

EXPLANATORY NOTES

A. Cytologic Diagnosis back Top Main Page
A modification of the Bethesda System,⁽¹⁾ which has been recommended for the classification of cervical cytologic findings, may also be used for reporting vulvar cytologic findings.

Cervical/Vaginal Cytologic Classification

SPECIMEN ADEQUACY

· Satisfactory for evaluation (describe presence or absence of endocervical/transformation zone component and any other quality indicators, e.g., partially obscuring blood, inflammation, etc.)

· Unsatisfactory for evaluation ... (specify reason)

· Specimen rejected/not processed (specify reason)

· Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason)

GENERAL CATEGORIZATION (optional)

· Negative for Intraepithelial Lesion or Malignancy

· Epithelial Cell Abnormality: See Interpretation/Result (specify ‘squamous’ or ‘glandular’ as appropriate)

· Other: See Interpretation/Result (e.g. endometrial cells in a woman ³ 40 years of age)

AUTOMATED REVIEW

If case examined by automated device, specify device and result.

ANCILLARY TESTING

Provide a brief description of the test methods and report the result so that it is easily understood by the clinician.

DESCRIPTIVE INTERPRETATIONS/DIAGNOSES

NEGATIVE FOR INTRAEPITHELIAL LESION OR MALIGNANCY (when there is no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result section of the report, whether or not there are organisms or other non-neoplastic findings)

ORGANISMS:

· Trichomonas vaginalis

· Fungal organisms morphologically consistent with Candida spp

· Shift in flora suggestive of bacterial vaginosis

· Bacteria morphologically consistent with Actinomyces spp.

· Cellular changes consistent with Herpes simplex virus

OTHER NON NEOPLASTIC FINDINGS (Optional to report; list not inclusive):

· Reactive cellular changes associated with

· inflammation (includes typical repair)

· radiation

· intrauterine contraceptive device (IUD)

· Glandular cells status post hysterectomy

· Atrophy

OTHER

· Endometrial cells (in a woman ³ 40 years of age)
(Specify if ‘negative for squamous intraepithelial lesion’)

EPITHELIAL CELL ABNORMALITIES

SQUAMOUS CELL

· Atypical squamous cells

· of undetermined significance (ASC-US)

· cannot exclude HSIL (ASC-H)

· Low grade squamous intraepithelial lesion (LSIL)
          encompassing: HPV/mild dysplasia/CIN 1 *

· High grade squamous intraepithelial lesion (HSIL)
          encompassing: moderate and severe dysplasia, CIS/CIN 2 and CIN 3

· with features suspicious for invasion (if invasion is suspected)

· Squamous cell carcinoma

GLANDULAR CELL

· Atypical

· endocervical cells (NOS or specify in comments)

· endometrial cells (NOS or specify in comments)

· glandular cells (NOS or specify in comments)

· Atypical

· endocervical cells, favor neoplastic

· glandular cells, favor neoplastic

· Endocervical adenocarcinoma in situ

· Adenocarcinoma

· endocervical

· endometrial

· extrauterine

· not otherwise specified (NOS)

OTHER MALIGNANT NEOPLASMS: (specify)

*Cellular changes of HPV cytopathic effect, previously termed “koilocytosis”, “koilocytotic atypia”, or “condylomatous atypia”, are included in the category of LSIL.

B. Histologic Type back Top Main Page
The following is an abbreviated, slightly modified version of the World Health Organization classification of histologic types of malignant and premalignant vulvar tumors.⁽²⁾

WHO Classification of Vulvar Epithelial Tumors and Related Lesions
Squamous lesions

• Intraepithelial neoplasia (vulvar intraepithelial

neoplasia: VIN)
- Mild dysplasia (VIN 1)
- Moderate dysplasia (VIN 2)
- Severe dysplasia (VIN 3)
- Carcinoma in situ (VIN 3)
• Squamous cell carcinoma
- Keratinizing
- Nonkeratinizing
- Basaloid
- Verrucous
- Warty (condylomatous)
- Others
• Basal cell carcinoma
Glandular lesions
• Paget’s disease
• Bartholin gland carcinoma
- Adenocarcinoma
- (squamous cell carcinoma)
- Adenoid cystic carcinoma
- Adenosquamous carcinoma
- (transitional cell carcinoma)
• Carcinoma resembling breast carcinoma
• Carcinoma of sweat gland origin
• Adenocarcinomas of other types

C. Depth of Invasion back Top Main Page
The depth of invasion of squamous cell carcinoma is defined as the measurement in mm from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.^(3-5) The depth of invasion of malignant melanoma is discussed in Note K.

D. Thickness of Tumor back Top Main Page
The thickness of a squamous cell carcinoma or a malignant melanoma is measured in mm from the surface of the tumor or, if there is surface keratinization, from the deep border of the granular layer to the deepest point of invasion.^(3,6-10)

E. Tumor Growth Pattern back Top Main Page
Vulvar squamous cell carcinomas can generally be separated into those tumors that have a predominately inflitrating (finger-like) pattern and those that invade with a broad, pushing front. Infiltrating invasion is associated with a higher frequency of regional lymph node metastasis and should be noted in the report.^(10,11)

F. Lymphatic/Blood Vessel Invasion back Top Main Page
Vascular space invasion by squamous cell carcinoma greater than 1 mm of depth of invasion may be associated with a higher frequency of regional lymph node metastasis and should be noted in the report.^(3,11,12)

G. Surgical Procedures (Designated by Surgeon) back Top Main Page
Procedures for partial excision or total vulvectomy as well as lymphadenectomy have been classified by the International Society for the Study of Vulvovaginal Disease⁽¹³⁾ as follows:

Vulvar procedures:

• Partial vulvectomy, superficial (“skinning” partial vulvectomy)

• Partial vulvectomy, deep (wide excision, wide “radical” excision)

• Total vulvectomy, superficial (“skinning” total vulvectomy)

• Total vulvectomy, deep “radical” vulvectomy without en bloc inguinal-femoral resection

• Total vulvectomy, deep, total, with contiguous en bloc inguinal - femoral lymphadenectomy

Lymphadenectomy procedures:

• Superficial inguinal-femoral lymphadenectomy

• Deep femoral lymphadenectomy (including node of Cloquet or Rosenmüller)

• Pelvic lymphadenectomy (including obturator and external and internal iliac nodes)

Other possible classifications are as follows:

• Local excision of gross disease (with 5 to 10 mm or larger margins)

• Wide local excision with resection of superficial underlying subcutaneous tissue

• Partial vulvectomy, superficial (superficial local excision; “skinning” partial vulvectomy

including epidermis and the superficial dermis)

• Total vulvectomy, superficial (encompasses superficial vulvectomy; extended skinning vulvectomy; “skinning” total vulvectomy)

• Radical local excision (encompasses partial vulvectomy, deep; deep local excision with superficial ipsilateral groin dissection)

• Radical hemivulvectomy with ipsilateral groin dissection

• Radical local excision with ipsilateral groin dissection (wide partial vulvectomy with

resection of superficial underlying subcutaneous tissue; wide local excision including excision to the fascia)

• Radical vulvectomy (total vulvectomy, deep, with bilateral groin dissection)

• Radical vulvectomy with bilateral groin dissection

• Radical local excision with bilateral groin dissection

• Nodal dissection

- contralateral groin node dissection following primary surgery

- pelvic node dissection, ipsilateral or bilateral

- paraaortic node dissection, (specify level or site)

• Pelvic exenteration

- anterior

- posterior

- total

• Radical anovulvectomy

• Radical vulvectomy with groin dissection with/without pelvic exenteration (anterior, posterior or total)

• Radical anovulvectomy with groin dissection, with/without pelvic node dissection.

H. TNM and Stage Groupings back Top Main Page

The TNM Staging System for carcinoma of the vulva of the American Joint Committee on Cancer and the International Union Against Cancer is recommended and is shown below.(14) Comparison with International Federation of Gynecology and Obstetrics (FIGO) staging is also shown.(15)

Primary Tumor (T)*

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Carcinoma in situ (pre-invasive carcinoma)

T1 Tumor confined to vulva or vulva and perineum, 2 cm or less in greatest dimension

T1a - with stromal invasion** < 1.0 mm

T1b - with stromal invasion** > 1 mm

T2 Tumor confined to the vulva or vulva and perineum, > 2 cm in greatest dimension

T3 Tumor invades any of the following: lower urethra, vagina, anus

T4 Tumor invades any of the following: bladder mucosa, rectal mucosa, upper urethral mucosa; or is fixed to pubic bone

*By AJCC/UICC convention, the designation "T" refers to a primary tumor that has not been previously treated. The symbol "p" refers to the pathologic classification of the TNM, as opposed to the clinical classification and is based on gross and microscopic examination. pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic examination of distant lesions.

Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.

Tumor remaining in a patient after definitive therapy (e.g., surgical resection for cure) is categorized by a system known as R classification, shown below.

RX Presence of residual tumor cannot be assessed

R0 No residual tumor

R1 Microscopic residual tumor

R2 Macroscopic residual tumor.

For the surgeon, the R classification may be useful to indicate the known or assumed status of the completeness of a surgical excision. For the pathologist, the R classification is relevant to the status of the margins of a surgical resection specimen. That is, tumor involving the resection margin on pathologic examination may be assumed to correspond to residual tumor in the patient and may be classified as macroscopic or microscopic according to the findings at the specimen margin(s).

In contrast, tumor remaining in a resection specimen from a patient who has undergone previous (neoadjuvant) treatment of any type (radiation therapy alone, chemotherapy therapy alone, or any combined modality treatment) is codified by the TNM using a prescript "y" (e.g., ypT1). Thus, yTNM indicates the post-treatment status of the tumor. For many neoadjuvant therapies, the classification of residual disease may be a strong predictor of postoperative outcome. In addition, the ypTNM classification provides a standardized framework for the collection of data needed to accurately evaluate new neoadjuvant therapies.

In contrast to "residual" tumor, classification of a tumor as "recurrent" requires a documented disease-free interval after definitive therapy. Recurrent tumor may also be classified according to the TNM categories, but the prefix "r" (e.g., rpT1) is used to indicate the recurrent status of the tumor.

**The depth of invasion is measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.

Regional Lymph Nodes (N)

NX Regional lymph nodes cannot be assessed

N0 No lymph nodes palpable

N1 Unilateral regional lymph node metastasis

N2 Bilateral regional lymph node metastasis

Distant Metastases (M)

MX Distant metastasis cannot be assessed

M0 No clinical metastasis

M1 Distant metastases (including pelvic lymph node metastasis)

TNM Stage Groupings and Correlation with
FIGO Staging

TNM FIGO

Stage 0 Tis N0 M0