Quick viewing(Text Mode)

CHAPTER 6 Tumours of the Vagina

CHAPTER 6 Tumours of the Vagina

CHAPTER 6

Tumours of the

Although the incidence rate of vaginal intraepithelial neoplasia is increasing, that of is decreasing, reflecting earlier detection and more successful treatment. Human papillomavirus infection is a risk factor for both vaginal intraepithelial neoplasia and squamous cell carcinoma.

In past decades, clear cell occurred in young women, about two-thirds of whom had been exposed transpla- centally to . At that time, it was the the most important glandular lesion of the vagina and the second most common epithelial . The precursor lesion appears to be atypical adenosis.

The most important non-epithelial tumours are malignant and botyoides. WHO histological classification of tumours of the vagina

Epithelial tumours Squamous tumours and precursors 8890/3 Squamous cell carcinoma, not otherwise specified 8070/3 Endometrioid stromal sarcoma, low grade 8931/3 Keratinizing 8071/3 Undifferentiated vaginal sarcoma 8805/3 Non-keratinizing 8072/3 8890/0 Basaloid 8083/3 Genital 8905/0 Verrucous 8051/3 Deep angiomyxoma 8841/1 Warty 8051/3 Postoperative spindle cell nodule Squamous intraepithelial neoplasia Vaginal intraepithelial neoplasia 3 / 8077/2 Mixed epithelial and mesenchymal tumours squamous cell carcinoma in situ 8070/2 (malignant müllerian mixed tumour; Benign squamous lesions metaplastic carcinoma) 8980/3 Condyloma acuminatum Adenosarcoma 8933/3 Squamous (vaginal micropapillomatosis) 8052/0 Malignant mixed tumour resembling 8940/3 Fibroepithelial polyp Benign mixed tumour 8940/0 Glandular tumours Clear cell adenocarcinoma 8310/3 Melanocytic tumours Endometrioid adenocarcinoma 8380/3 Malignant melanoma 8720/3 Mucinous adenocarcinoma 8480/3 Blue naevus 8780/0 Mesonephric adenocarcinoma 9110/3 Melanocytic naevus 8720/0 Müllerian papilloma Adenoma, not otherwise specified 8140/0 Miscellaneous tumours Tubular 8211/0 Tumours of germ cell type Tubulovillous 8263/0 Yolk sac tumour 9071/3 Villous 8261/0 Dermoid cyst 9084/0 Other epithelial tumours Others Adenosquamous carcinoma 8560/3 Peripheral primitive neuroectodermal tumour / 9364/3 Adenoid cystic carcinoma 8200/3 Ewing tumour 9260/3 Adenoid basal carcinoma 8098/3 Adenomatoid tumour 9054/0 Carcinoid 8240/3 Small cell carcinoma 8041/3 Lymphoid and haematopoetic tumours Undifferentiated carcinoma 8020/3 Malignant lymphoma (specify type) Leukaemia (specify type) Mesenchymal tumours and tumour-like conditions 8910/3 Secondary tumours

______1 Morphology code of the International Classification of Diseases for (ICD-O) {921} and the Systematized Nomenclature of Medicine (http://snomed.org). Behaviour is coded /0 for benign tumours, /2 for in situ carcinomas and grade 3 intraepithelial neoplasia, /3 for malignant tumours, and /1 for borderline or uncertain behaviour. 2 Intraepithelial neoplasia does not have a generic code in ICD-O. ICD-O codes are only available for lesions categorized as squamous intraepithelial neoplasia grade 3 (e.g. vaginal intraepithelial neoplasia/VAIN grade 3) = 8077/2; squamous cell carcinoma in situ = 8070/2. TNM and FIGO classification of carcinomas of the vagina

TNM and FIGO classification 1,2 N – Regional Lymph Nodes 3 T – Primary Tumour NX Regional lymph nodes cannot be assessed N0 No regional TNM FIGO N1 Regional lymph node metastasis Categories Stages M – Distant Metastasis TX Primary tumour cannot be assessed MX Distant metastasis cannot be assessed T0 No evidence of primary tumour M0 No distant metastasis Tis 0 Carcinoma in situ (preinvasive carcinoma) M1 Distant metastasis T1 I Tumour confined to vagina T2 II Tumour invades paravaginal tissues but does Stage Grouping not extend to pelvic wall Stage 0 Tis N0 M0 T3 III Tumour extends to pelvic wall Stage I T1 N0 M0 T4 IVA Tumour invades mucosa of bladder or rectum, Stage II T2 N0 M0 and/or extends beyond the true pelvis Stage III T3 N0 M0 Note: The presence of bullous oedema is not sufficient evidence to classify a T1, T2, T3 N1 M0 tumour as T4. Stage IVA T4 N0 M0 M1 IVB Distant metastasis Stage IVB Any T Any N M1

______1 {51,2976}. 2 A help desk for specific questions about the TNM classification is available at http://tnm.uicc.org. 3 The regional lymph nodes are: Upper two-thirds of vagina: the pelvic nodes including obturator, internal iliac (hypogastric), external iliac, and pelvic nodes, NOS. Lower third of vagina: the inguinal and femoral nodes.

292 Tumours of the vagina E.S. Andersen A.G. Hanselaar Epithelial tumours J. Paavonen C. Bergeron M. Murnaghan S.P. Dobbs A.G. Östör

Squamous tumours interval is re q u i red to rule out re c u r re n t Clinical features disease in those patients with a prior Signs and symptoms Definition p reinvasive or invasive cervical or vulvar The commonest symptom is a bloody Primary squamous epithelial tumours of . vaginal discharge. Nearly 75% of the vagina are the most frequent neo- patients present with painless bleeding, plasms at this site. They occur in all age Epidemiology u r i n a ry tract symptoms or postcoital groups but preferentially in the elderly. Squamous cell carcinoma comprises up bleeding; however, the patient may be Vaginal intraepithelial neoplasia (VAIN) is to 85% of vaginal carcinomas and completely asymptomatic. Pelvic pain considered a typical, though not obliga- accounts for 1-2% of all malignant and dysuria usually signify advanced tory, precursor lesion of squamous cell tumours of the female genital tract {634, disease {2499}. Most cases occur in the carcinoma. 1193}. The mean age of patients is about upper third of the vagina and are located 60 years. on the posterior wall {2265}. ICD-O codes Squamous cell carcinoma 8070/3 Aetiology Imaging Vaginal intraepithelial neoplasia In squamous cell carcinoma persistent Magnetic resonance imaging (MRI) of (VAIN), grade 3 8077/2 infection with high-risk human papillo- the pelvis can be used to image vaginal Squamous cell carcinoma in situ 8070/2 mavirus (HPV) is probably a major aetio- tumours as well as to assess whether Squamous papilloma 8052/0 logical factor. The same risk factors are pelvic or inguinal lymphadenopathy is observed as for vaginal intraepithelial present. The MRI appearance, however, Squamous cell carcinoma neoplasia (VAIN), i.e. previous preinva- is not specific, and inflammatory sive or invasive disease of the lower gen- changes and congestion of the vagina Definition ital tract, immunosuppression and prior may mimic vaginal carcinoma {439}. An invasive carcinoma composed of pelvic irradiation {303}. The development squamous cells of varying degrees of of VAIN and eventual progression to inva- Exfoliative cytology d i ff e rentiation. According to the sive disease is most likely, though the Occasionally, cancer cells of vaginal ori- I n t e rnational Federation of Gynaecology progression rate is unknown {347}. gin may be observed in cervical smears. and Obstetrics (FIGO), a tumour of the Prior pelvic irradiation is a predisposing vagina involving the uterine cervix or the factor for vaginal squamous carcinoma Macroscopy vulva should be classified as a primary {303,748,3075}. Simultaneous or prior Tumours may be exophytic, ulcerative or cervical or , re s p e c t i v e l y. p reinvasive or invasive disease else- annular and constricting. The lesions A d d i t i o n a l l y, before the diagnosis of a w h e re in the lower genital tract is vary in size from being undetectable to p r i m a ry vaginal carcinoma can be observed in up to 30% of cases greater than 10 cm. They may be poly- established, a 5-10 year disease fre e {220,2227,2480}. poid, sessile, indurated, ulcerated or fun-

A B Fig. 6.01 Squamous cell carcinoma. A Keratinizing type. Carcinoma arises from the surface epithelium and forms several keratin pearls. B Non-keratinizing type. The neo- plasm forms prominent squamous pearls with little keratinization.

Epithelial tumours 293 Table 6.01 Terminology of premalignant vaginal squamous epithelial lesions.

Classification Synonyms Vaginal intraepithelial Mild dysplasia Low grade VAIN neoplasia, grade 1

Vaginal intraepithelial Moderate dysplasia High grade VAIN neoplasia, grade 2

Vaginal intraepithelial Severe dysplasia High grade VAIN Fig. 6.02 Vaginal intraepithelial neoplasia, grade 2. neoplasia, grade 3 and carcinoma in situ Nuclear features of intraepithelial neoplasia are evi- dent in the lower two-thirds of the squamous epithe- VAIN = vaginal intraepithelial neoplasia lium with overlying parakeratosis. gating and may be found anywhere with- , liver and brain. The staging of middle or lower third of the vagina the in the vagina. Squamous cell carcinoma, vaginal tumours is by the TNM/FIGO external radiation field should include the the commonest vaginal carcinoma, is classification {51,2976}. Appro x i m a t e l y inguinal and femoral lymph nodes. ulcerative in half of cases, exophytic in a 25% of patients present with stage I dis- The clinical stage is the most significant third and annular and constricting in the ease, one-third with stage II disease and p rognostic factor {220,748,1245,1524, remainder. 40% with stage III or IV disease {220,748, 2301,2480}. Recurrences are typically 1245,1524,2301,2480}. local and usually happen within 2 years Tumour spread and staging of treatment. The five-year survival rates Squamous cell carcinoma spreads pre- Histopathology are 70% for stage I, 45% for stage II, dominantly laterally to the paravaginal Vaginal squamous cell carcinoma has 30% for stage III and 15% for stage IV. and parametrial tissues when located in the same histological characteristics as The overall 5-year survival is about 42% the lower and upper vagina, respectively. such tumours in other sites. Most cases {220,748,1245,1524,2301,2480}. Tumours also invade lymphatics, metas- are moderately differentiated and non- Tumour localization, grade or keratiniza- tasizing to regional lymph nodes and keratinizing {2301}. Rarely, the tumours tion or patient age has not been demon- eventually distant sites including the have spindle-cell features {2778}. Warty strated to have prognostic significance. carcinoma is another variant of vaginal squamous cell carcinoma {2339}. The Vaginal intraepithelial neoplasia tumour is papillary with hyperkeratotic epithelium. Nuclear enlargement and Definition koilocytosis with hyperchromasia, wrin- A premalignant lesion of the vaginal kling of the nuclear membrane and mult- squamous epithelium that can develop inucleation are typical changes {1541, primarily in the vagina or as an extension 2936}. Verrucous carcinoma has a papil- from the cervix. VAIN is often a manifes- lary growth pattern with pushing borders tation of the so-called lower genital tract and bulbous pegs of acanthotic epitheli- neoplastic syndrome. Histologically, um with little or no atypia and surface VAIN is defined in the same way as cer- maturation in the form of parakeratosis vical intraepithelial neoplasia (CIN). and hyperkeratosis. For a more detailed discussion of the subypes of squamous Synonyms cell carcinoma see chapter 5 or 7. Dysplasia/carcinoma in situ, squamous intraepithelial lesion. Prognosis and predictive factors Radiation is the preferred treatment for Epidemiology most cases of vaginal carcinoma {1524, VAIN is much less common than CIN, 2217,2981}. In Stage I disease located in though its true incidence is unknown. the upper part of the vagina, a radical Th e r e is some evidence that the inci- hysterectomy, pelvic lymphadenectomy dence of VAIN has increased in rec e n t and partial vaginectomy may be consid- decades, particularly among young and ered {55,171}. Otherwise, radiation thera- im m u n o s u p p r essed women. The mean py given as intracavitary therapy, intersti- age for patients with VAIN is approx i m a t e - Fig. 6.03 Vaginal intraepithelial neoplasia, grade3. tial implants and/or extern a l ly 50 years. The majority of VAIN cases The upper portion of the epithelium is covered by pelvic/inguinal radiation, often in combi- occur in women who have had a prior hyperkeratosis. The remaining cells are character- nation, is the most frequently adopted hy s t e r ectomy or who have a history of ized by nuclear enlargement and pleomorphism. modality {1524,2217}. In tumours of the cervical or vulvar neoplasia {1626, 2403}.

294 Tumours of the vagina Aetiology The fact that both VAIN and vaginal car- cinoma are much less common than cer- vical neoplasia has been explained by the absence of a vulnerable transforma- tion zone in the vagina. VAIN is associat- ed with HPV infection in most cases. At least 15 different HPV types have been identified in VAIN. As in the cervix, VAIN 2 and VAIN 3 are associated with high- risk HPV types, of which type 16 is the most frequent. Mixed HPV types have also been identified in multifocal VAIN lesions and also in a single lesion {239, 2565}. In VAIN 1 a mixture of low and high-risk HPV types can be detected.

Clinical features Signs and symptoms VAIN may be isolated but is more common- ly multifocal {710,1626}. Isolated lesions are mainly detected in the upper one-third of the vagina and in the vaginal vault after Fig. 6.04 Condyloma acuminatum. Papillomatosis, Fig. 6.05 Spiked condyloma. Papillomatosis is hy s t e re c t o m y . VAIN is asymptomatic and acanthosis and hyperkeratosis are associated with associated with HPV-infected cells with a clear cannot be diagnosed by the naked eye. a few in the superficial layers. cytoplasm (koilocytes).

Colposcopy show hyperkeratosis. The so-called "flat Prognosis and predictive factors VAIN may be suspected by a cervico- condyloma" shows koilocytosis in the The natural history of VAIN has been less vaginal cytology preparation, but the superficial layers of the epithelium with extensively studied than that of CIN. In diagnosis can only be made by a colpo- normal or only hyperplastic basal layers one study 23 patients with a mean age of scopically directed biopsy. If the col- without nuclear atypia.However, the dis- 41 years were followed for at least 3 poscopy of the cervix is normal after an tinction between flat condyloma and years with no treatment {49}. One-half of abnormal cytological smear, a careful VAIN 1 with koilocytosis is not always the VAIN lesions were multifocal. colposcopic examination of all the vagi- possible. Other differential diagnoses of Progression to invasive vaginal carcino- nal epithelium should be perf o rm e d . VAIN include atrophy, squamous atypia ma occurred in only 2 cases, and VAIN VAIN lesions are always iodine-negative. and transitional cell metaplasia {3085} as persisted in 3 additional cases. Thus, The presence of punctation on a sharply well as immature squamous metaplasia VAIN spontaneously regressed in 78% of demarcated aceto-white area is the sin- in women with adenosis. A distinction is cases. A re t rospective review of 121 gle most reliable colposcopic feature made based on the nuclear features of women with VAIN showed that the recur- suggestive of VAIN {2565}. the epithelium. rence rate was 33% {710}. Progression to The relationship of the VAIN term i n o l o g y invasive occurred in 2%. Histopathology to that of dysplasia and carcinoma in In another study of 94 patients with VAIN, The histopathology of VAIN is similar to situ of the vagina is shown in Ta b l e the progression rate to cancer was 5% that of CIN. Many VAIN 3 lesions also 6 . 0 1 . {2674}.

Fig. 6.06 Vaginal intraepithelial neoplasia, grade1. Fig. 6.07 Flat condyloma. Note the cytopathic Fig. 6.08 Atrophy. The cells are small, accounting Note the koilocytosis and the slightly thickened effects of human papilomavirus (koilocytosis) with for the nuclear crowding. Nuclei are uniform with and disorganized basal layers. a normal basal layer of the squamous epithelium. discernible nucleoli. Mitoses are not detectable.

Epithelial tumours 295 High grade VAIN appears to be an Clinical features Histopathology important precursor of invasive cancer; Signs and symptoms Condyloma acuminatum has a complex, progression occurred in 8% of cases of Vaginal lesions are easily overlooked arborizing architecture with hyperkerato- high grade VAIN despite the fact that during a speculum examination. Vaginal sis, parakeratosis, acanthosis and papil- most of the patients were treated, where- condylomas present in the same way as lomatosis as well as the typical cytopath- as low grade VAIN regressed in 88% of those on the vulva and the cervix {1070, ic effects of HPV. It can be distinguished women without treatment {2403}. 2144}. They can be single or multiple. by clinical examination alone from vagi- Condylomas can cover most of the vagi- nal micropapillomatosis, which has no Condyloma acuminatum nal mucosa and extend to the cervix and significant relationship with HPV infection may be small or large. Most commonly, and is believed by some to be a normal Definition they occur adjacent to the introitus and in anatomical variant of the lower genital A benign neoplasm characterized by the vaginal fornices. Condylomas can be tract {967}. The latter also lacks the his- papillary fronds containing fibrovascular papular or macular. The latter has been tological features of condyloma. cores and lined by stratified squamous also called "flat condyloma", noncondylo- epithelium with evidence of HPV infec- matous virus infection or subclinical Squamous papilloma tion, usually in the form of koilocytosis. papillomavirus infection. Definition Epidemiology A benign papillary tumour in which squa- Condylomas are sexually transmitted. Typical exophytic condylomas show mous epithelium without atypia or koilo- Th e r e is strong evidence that their inci- digitate projections with vascularized cytosis lines a fibrovascular stalk. dence has increased since the 1960s. c o res producing loop-like patterns or The incidence is much higher in women punctation {1070,2144}. The applica- Synonyms than in men. They often occur on the tion of acetic acid augments the diag- Vaginal micropapillomatosis, squamous mucosal epithelium of the vagina. How- nosis of vaginal condylomas. Micro - papillomatosis. ev e r , because condylomas are often sub- p a p i l l a ry vaginal condylomas may be These terms are applicable when numer- clinical and not rep o r ted, their true inci- d i ffuse and may completely cover the ous lesions are present. dence remains unknown. vagina. This manifestation is known as condylomatous vaginitis. Reverse Epidemiology Aetiology punctation can be seen by colposcopy Squamous do not appear to Non-oncogenic HPV types 6 and 11 are after acetic acid application. Spiked be sexually transmitted. found in the majority of condylomas condylomas appear as small and elon- {1837}. Patients with visible condylomas gated white spikes focally or diff u s e l y Aetiology can be simultaneously infected by other distributed on the vaginal wall {1070, Based on in situ hybridization studies HPV types (mixed HPV infection). 2 1 4 4 } . using the polymerase chain re a c t i o n , vaginal micro p a p i l l a ry lesions appear un r elated to human papillomavirus {967}, and their aetiology is unknown.

Clinical features Squamous papillomas may be single or multiple. When numerous, they occur near the hymenal ring and are referred to as vaginal micropapillomatosis. The lesions are usually asymptomatic but may be associated with vulvar burning or dyspareunia. They may be difficult to dis- tinguish from condyloma by inspection. However, on colposcopic and histologi- cal examination papilloma is composed of a single papillary frond with a central fibrovascular. core.

Histopathology In squamous papilloma the squamous epithelium covers a central fibrovascular core and shows acanthosis but lacks koilocytosis. It has a smooth surface and lacks significant vascular structures. It Fig. 6.09 Squamous papilloma. The fibrovascular core is covered by squamous epithelium with a smooth sur- lacks the complex arborizing architec- face that lacks koilocytosis but shows acanthosis and papillomatosis. t u re and koilocytes of condylomas.

296 Tumours of the vagina Mucinous adenocarcinoma 8480/3 in several countries, including the United Mesonephric adenocarcinoma 9110/3 States, France and the Netherlands Adenoma, NOS 8140/0 {2946}. DES is a teratogen and causes a Tubular 8211/0 variety of congenital abnormalities of the Tubulovillous 8263/0 lower genital tract in about 30% of the Villous 8261/0 female offspring {1883}. The absolute risk of clear cell adenocarcinoma of the vagi- Clear cell adenocarcinoma na or cervix is estimated at 1:1000 {1843}. About two-thirds of the cases of Definition clear cell adenocarcinoma occurring in An invasive neoplasm with an epithelial individuals under the age of 40 are linked Fig. 6.10 Fibroepithelial polyp.A multilobulated poly- poid lesion arises from the vaginal wall. component that contains one or more cell to transplacental DES exposure. DES types, most commonly clear cells and inhibits the development of urog e n i t a l hobnail cells, but flat and/or eosinophilic sinus-derived squamous epithelium that However, it is important to note that there cells may, on occasion, pred o m i n a t e . is destined to become may be a time during the evolution of and normally grows up to the junction of condylomas when koilocytes are not eas- Epidemiology the ectocervix and endocervix, rep l a c i n g ily identifiable. The occurrence of cases of vaginal clear the pre-existing müllerian-derived colum- cell adenocarcinoma associated with in nar epithelium. The embryonic müllerian Fibroepithelial polyp ut e r o exposure to diethylstilbestrol (DES) epithelium that is not replaced persists was responsible for an increase in inci- and develops into adenosis. Adenosis is Definition dence of adenocarcinoma in young found immediately adjacent to the tumour A polyp lined by squamous epithelium women from the 1970s {1194}. In the early in over 90% of cases and is thought to be that contains a central core of fibrous tis- 1970s the peak incidence of clear cell the precursor of clear cell adenocarci n o - sue in which stellate cells with tapering ad e n o c a r cinoma was around 19 years, ma. The rarity of clear cell adenocarci n o - cytoplasmic processes and irregularly the youngest patient being 8 years. With ma in the exposed population suggests shaped thin-walled vessels are promi- the ageing of the DES-exposed cohort, that DES is an incomplete carcinogen or nent features. the peak incidence has been shifting that susceptibility factors are necessary to w a r ds an older age group. for it to produce neoplastic transforma - Synonym tion. Genetic factors and hormonal dis- Stromal polyp. Aetiology ruption by environmental toxins are impli- DES was prescribed for threatened or cated. A maternal history of prior sponta- Clinical features repeated abortions from the 1940s to the neous abortion increases the risk of clear This lesion can occur at any age but has early 1970s. Millions of women were cell adenocarcinoma {2161}. Endoge- a predilection for pregnant women. exposed in utero to this and related drugs nous estrogens probably also play a rol e ,

Macroscopy These are polypoid lesions, usually solitary.

Histopathology These polypoid lesions are characterized by a prominent fibrovascular stroma cov- e red by squamous epithelium {380}. They lack epithelial acanthosis and pap- illary architecture. Bizarre stromal cells, marked hypercellularity and elevated mitotic counts including atypical forms have been described that can lead to an erroneous diagnosis of sarcoma botry- oides, but a cambium layer and rhab- domyoblasts are absent, and mitotic activity is typically low {2067}.

Glandular tumours and their precursors

ICD-O codes Adenocarcinoma, NOS 8140/3 A B Clear cell adenocarcinoma 8310/3 Fig. 6.11 Fibroepithelial polyp. A This polypoid lesion is composed of stroma and covered by squamous Endometrioid adenocarcinoma 8380/3 epthelium. B The stroma contains scattered bizarre multinucleated giant cells.

Epithelial tumours 297 A B Fig. 6.12 Adenosis of the vagina. A By colposcopy red granular areas of adenosis are apparent. B Colposcopy after iodine application. The areas of adenosis do not stain. since most cases of clear cell adenocar- detection, but care must be taken to ing in the cervix, endometrium and . cinoma are first detected around the time sample the vagina as well as the cervix Clear cell may show of puberty . since cervical smears are re l a t i v e l y several growth patterns; the most com- insensitive for the detection of clear cell mon pattern is tubulocystic, but it also Localization a d e n o c a rcinoma {1132}. may be solid or mixed. A papillary growth Whilst any part of the vagina may be Clear cell adenocarcinomas typically pattern is seldom predominant. The main involved, clear cell adenocarcinoma most a re polypoid, nodular, or papillary but cell types are clear cells and hobnail often arises from its upper part. A primary may also be flat or ulcerated. Some cells. The appearance of the clear cells vaginal clear cell adenocarcinoma may clear cell adenocarcinomas are con- is due to the presence of abundant intra- also involve the cervix. According to FIGO fined to the superficial stroma and cytoplasmic glycogen. Hobnail cells are criteria about two-thirds of clear cell ade- may remain undetected for a long time characterized by inconspicuous cyto- no c a r cinomas after DES exposure are {1131,2386}. Such small tumours may plasm and a bulbous nucleus that pro- classified as tumours of the vagina and be invisible on macroscopic or even col- trudes into glandular lumens. The tumour on e - t h i r d of the cervix {1131}. In non-DES poscopic examination and are only cells may also be flat with bland nuclei exposed young women and post- detected by palpation or when tumour and scant cytoplasm in cystic areas or menopausal women this ratio is rev e r s e d . cells are shed through the mucosa and have granular eosinophilic cytoplasm detected by exfoliative cytology. Large without glycogen. The nuclei vary con- Clinical features tumours may be up to 10 cm in diameter. siderably in appearance. They may be , discharge and dys- significantly enlarged with multiple irreg- p a reunia are the most common symp- Histopathology ular nucleoli in clear and hobnail cells, or toms, but women may be asymptomatic. Clear cell adenocarcinoma of the vagina they may have fine chromatin and incon- A b n o rmal cytologic findings may lead to has an appearance similar to those aris- spicuous nucleoli in flat cells. The num-

A B Fig. 6.13 Clear cell adenocarcinoma. A Note the neoplastic tubules lined by hobnail cells on the right and adenosis of the tuboendometrial type on the left. B Cytological preparation shows hobnail cells with anisonucleosis, unevenly distributed chromatin, nucleoli and vacuolated cytoplasm.

298 Tumours of the vagina ber of mitoses varies but is usually less than 10 per 10 high power fields. Psammoma and intracellular hyaline bodies may occasionally be encoun- tered.

Cytopathology In cytological preparations the malignant cells may occur singly or in clusters and resemble large endocervical or endome- A trial cells. Typically, the nuclei are large with one or more prominent nucleoli. Nuclei may be bizarre. The bland cyto- logical features of tumours that show only mild nuclear atypia may, however, ham- per cytological detection.

Prognosis and predictive factors Clear cell adenocarcinoma may be treat- ed by radical hysterectomy, vaginectomy and lymphadenectomy or by external B beam or local radiotherapy. The tumour Fig. 6.14 Adenosis of the vagina. A Note the tubo- Fig. 6.15 Submucosal atypical adenosis of the vagi- spreads primarily by local invasion and endometrioid type glands. B On the surface within na. Note the nuclear enlargement and atypia in the lymphatic metastases and has a recur- adenosis is a focus of squamous metaplasia . glands. rence rate of 25%. The incidence of lymph node disease increases dramati- cally with tumour invasion beyond 3 mm Localization Adenosis can be detected on cytological in depth. Lymph node metastases occur The most frequent site of involvement is examination by the finding of columnar or in 16% of patients with stage I disease the anterior upper third of the vagina. metaplastic squamous cells in scrapes and 50% of those with stage II disease. of the middle and upper third of the vagi- Haematogenous metastasis to distant Clinical features na. However, similar findings may occur organs occurs mainly to the lungs. The Signs and symptoms in non-DES-exposed women as a result 5-year survival of patients with tumours of Adenosis is usually asymptomatic. Some of contamination of the vaginal specimen all stages is approximately 80% and is women present with a mucous dis- by columnar or metaplastic squamous close to 100% for patients with stage I charge, bleeding or dyspare u n i a . . cells from the cervix. tumours. Most recurrences occur within 3 Adenosis may spontaneously regress at years. Long disease-free intervals of the surface and be replaced by meta- Histopathology more than 20 years have been observed. plastic squamous epithelium, particularly Adenosis is characterized by the pres- Factors associated with a favourable with increasing age. Because of the risk ence in the vagina of columnar epitheli- prognosis are: low stage, small tumour of development of clear cell adenocarci- um resembling mucinous epithelium of size, a tubulocystic pattern, low mitotic noma within the vaginal wall, palpation, the endocervix (mucinous type) and/or activity and mild nuclear atypia. colposcopic examination and cytological the endometrium or the fallopian tube smears are necessary to monitor patients (tuboendometrial type). Adenosis may Adenosis with adenosis. be found on the surface or deeper in the stroma. Mixtures of the various types of Definition Colposcopy adenosis may be encountere d . Adenosis is the presence of glandular Areas of adenosis and associated squa- Squamous metaplasia may occur as a epithelium in the vagina and is thought to mous metaplasia may be visible colpo- result of healing. be the result of the persistence of embry- scopically and by iodine staining {2046}. onic müllerian epithelium. Adenosis may be occult or may present Atypical adenosis as cysts or as a diffusely red granular Epidemiology area. Definition Adenosis has been reported to occur in Atypical adenosis is the presence of approximately 30% of women after in Cytology atypical glandular epithelium in the vagi- u t e ro exposure to DES. Congenital Cytology can be helpful in the diagnostic na. It is reported to be a precursor lesion adenosis may be present in up to 8% of evaluation of DES-exposed women (see of clear cell adenocarcinoma. unexposed women. Adenosis has been below). It may serve a dual purpose, as a described after vaporization or means for detection of adenocarcinoma Histopathology intravaginal application of 5-fluorouracil or as a follow-up procedure after treat- Atypical adenosis occurs in the tuboen- {730}. ment of the lesion. dometrial type of adenosis and is a fre-

Epithelial tumours 299 cell adenocarcinoma, mesonephric carci - noma does not contain clear or hobnail cells, intracellular mucin or glycogen, and the tubules are often surrounded by a basement membrane.

Müllerian papilloma

Müllerian papilloma may arise in the vagina of infants and young women {2977} (see also chapter on the cervix). A few examples have arisen in the wall of the vagina {1817}. Occasional local recurrences have been reported {1719}, and in one instance repeated removal of recurrent müllerian papillomas was nece- ssary {708}. The origin of the tumour is not clear, although reports support a mül- lerian origin {1719}.

Fig. 6.16 Mesonephric remnants. The wall of the vagina contains clusters of uniform dilated tubules with Tubular, tubulovillous and villous luminal hyaline material. adenoma

Definition Benign glandular tumours with enteric quent finding immediately adjacent to been described in association with ade- differentiation {494}. clear cell adenocarcinoma. The atypical nosis as well as cases arising in vaginal glands tend to be more complex than endometriosis {1155,3251}. Clinical features those of mucinous adenosis and are Patients may be premenopausal or post- lined by cells with enlarged, atypical, Mucinous adenocarcinoma menopausal. Clinical examination may pleomorphic, hyperchromatic nuclei that reveal a polypoid mass. contain prominent nucleoli. Mitotic fig- P r i m a ry mucinous adenocarcinoma of ures are infrequent, and hobnail cells the vagina is rare. Only a few cases Histopathology may be present. have been re p o rted {745}. Like the other The adenomas are histologically similar non-clear cell adenocarcinomas of the to colonic types and have been subclas- Differential diagnosis vagina, this type of tumour is pre d o m i- sified as tubular, tubulovillous or villous. A distinction from clear cell adenocarci- nantely re p o rted in peri-menopausal The epithelium is stratified and contains noma may be difficult if the atypical women. Histologically, the tumour may columnar cells with mucin. The nuclei are adenosis shows a pseudoinfiltrative pat- resemble typical endocervical or intes- oval to elongated and dysplastic. tern of small glands. Conversely, clear tinal adenocarcinomas of the cervix Adenocarcinoma arising from a vaginal cell adenocarcinoma displaying a tubu- {909}. Due to its rarity, little is known adenoma has been reported {1935}. locystic pattern may be erro n e o u s l y about its aetiology and behaviour. A interpreted as adenosis. However, unlike relationship to vaginal adenosis has Differential diagnosis tubulocystic clear cell adenocarcinoma been described {3168}, suggesting a Aside from endometriosis and prolapsed with bland flattened cells, atypical müllerian origin. An unusual variant of fallopian tube, the most important lesions adenosis is composed of cuboidal or mucinous adenocarcinoma has been in the differential diagnosis are metastat- columnar epithelium. described in neovaginas {1218,1941}. ic carcinoma and extension or recur- rence of endometrial or endocervical Prognosis and predictive factors Mesonephric adenocarcinoma adenocarcinoma. An adenoma is gener- Management may be local excision or ally polypoid and lacks invasive borders, follow-up {2609}. Mesonephric (Gartner) duct remnants are marked architectural complexity or high mostly situated deep in the lateral walls of grade cytological features. Endometrioid adenocarcinoma the vagina. Only a few cases of carci n o - ma arising from mesonephric remnants in Uncommon epithelial tumours Only a few primary endometrioid adeno- the vagina have been rep o r ted, and none carcinomas of the vagina have been since 1973. These tumours are com- Definition reported. The histological appearance posed of well-formed tubules lined by Primary epithelial tumours of the vagina resembles that of the much more com- atypical, mitotically-active, cuboidal to other than those of squamous or glandu- mon endometrioid adenocarcinoma of columnar epithelium that re s e m b l e lar type. These tumours are described in the endometrium. A few cases have mesonephric duct remnants. Unlike clear more detail in the chapter on the cervix.

300 Tumours of the vagina ICD-O codes Adenoid cystic carcinoma Carcinoid Adenosquamous carcinoma 8560/3 Adenoid cystic carcinoma 8200/3 An adenocarcinoma which re s e m b l e s A tumour resembling carcinoids of the Adenoid basal carcinoma 8098/3 adenoid cystic carcinoma of salivary gastrointestinal tract and {936}. Carcinoid 8240/3 gland origin but usually lacks the myoep- Small cell carcinoma 8041/3 ithelial cell component of the latter Small cell carcinoma Undifferentiated carcinoma 8020/3 {2781}. A carcinoma of neuroendocrine type that Adenosquamous carcinoma Adenoid basal carcinoma resembles small cell carcinomas of the lung {1371,1869,1877,2281}. A carcinoma composed of a mixture of A carcinoma with rounded, generally well malignant glandular and squamous d i ff e rentiated nests of basaloid cells Undifferentiated carcinoma epithelial elements {2360}. showing focal gland formation; central squamous differentiation may be present A carcinoma that is not of the small cell as well {1906,1986}. type and lacks evidence of glandular, squamous, neuroendocrine or other types of differentiation.

Epithelial tumours 301 Mesenchymal tumours A.G. Östör

Vaginal shaped cells, some of which show evi- fication is used, which is based on the dence of striated muscle differentiation. combined features of extent of disease, Definition resectability and histological evaluation Malignant mesenchymal tumours that Synonym of margins of excision {99}. arise in the vagina. Embryonal . Histopathology ICD-O codes Epidemiology The neoplasm is composed of cells with Sarcoma botryoides 8910/3 Sarcoma botryoides (Greek bothryos: round to oval or spindle-shaped nuclei Leiomyosarcoma 8890/3 grapes) is the most common vaginal sar- and eosinophilic cytoplasm that may show Endometrioid stromal sarcoma, coma and occurs almost exclusively in d i ff e rentiation towards striated muscle low grade 8931/3 ch i l d r en and infants <5 years of age (mean cells. Typ i c a l l y , there is a dense cambium Undifferentiated vaginal sarcoma 8805/3 1.8 years) {633}, although occasional layer composed of closely packed cells cases are encountered in young adults or with small hyperch r omatic nuclei immedi- Epidemiology even postmenopausal women. At least two ately subjacent to the squamous epitheli- Sarcomas are rare and comprise <2% of cases of sarcoma botryoides have been um that may be invaded. The nuclei have all malignant vaginal {633}. described in pregnancy {2709}. an open chromatin pattern and inconspic- uous nucleoli. The central portion of the Aetiology Clinical features polypoid mass is typically hypocellular, There are virtually no clues to the patho- These tumours present typically as a oedematous or myxomatous. The mitotic genesis of this group of tumours. vaginal mass that on clinical and macro- rate is high. Rhabdo-myoblasts (strap scopic examination appears soft, oede- cells), which may be sparse, may be Clinical features matous and nodular, papillary, polypoid found in any of the patterns. Their rec o g n i - Signs and symptoms or grape-like, often protruding through tion may be facilitated by immunohisto- Malignant tumours usually present with the introitus. chemical staining with antibodies direc t e d bleeding and/or discharge and a mass against actin, or myoglobin. and are usually readily detected by clini- Macroscopy Although the first two antibodies are more cal examination. Occasional cases are The tumours vary from 0.2-12 cm in max- sensitive than myoglobin, they are not detected by an abnormal cytological imum dimension and may be covered by specific for diffe re n t i a t i o n . examination. Some sarcomas, however, an intact mucosa or be ulcerated and Ultrastructural examination may rev e a l are asymptomatic, and the diagnosis is, bleeding. The sectioned surface dis- characteristic features of rhabdomyoblas- therefore, delayed. plays grey to red areas of myxomatous tic diffe r entiation, such as thick and thin fil- change and haemorrhage. aments with Z-band material. Imaging The extent of tumour spread may be Tumour spread and staging Differential diagnosis determined by transvaginal ultrasound. In children the Intergroup Rhabdo- The distinction from a benign fibroepithe- Study group clinical classi- lial polyp with bizarre nuclei is important. Tumour spread and staging Vaginal sarcomas spread by dire c t extension and by metastasis; the latter Table 6.02 Clinical classification of vaginal sarcoma botyroides / rhabdomyosarcoma {99}. occurs both by lymphatic and haema- togenous routes. The tumour initially I Complete surgical resection grows into the vaginal wall and of the pelvis, bladder or rectum. The IIa Excision, margin positive staging of vaginal sarcomas in adults uti- lizes the TNM/FIGO classification IIb Excision, lymph nodes positive {51,2976}. IIIa Biopsy only Sarcoma botryoides IIIb Partial surgical excision (gross disease present) Definition A malignant mesenchymal tumour com- IV Metastatic disease posed of small, round or oval to spindle-

302 Tumours of the vagina operative spindle cell nodule {2861}. The latter is a localized non-neoplastic lesion composed of closely packed spindle-shaped cells and capillaries occurring several weeks to several months postoperatively in the region of an excision. It may closely resemble a l e i o m y o s a rcoma, but the history of a recent operation at the same site facili- A B tates its diagnosis. Prognosis and predictive factors are treated primarily by radical surgical excision (vaginecto- m y, hysterectomy and pelvic lym- phadenectomy). In the only large series of 60 tumours, both benign and malignant, only 5 neoplasms recurred, and in one of these, a tumour- with an infiltrative margin, the patient C D died of lung metastases {2879}. Fig. 6.17 Sarcoma botryoides. A Polypoid masses of tumour are covered by squamous epithelium. B A subepithelial cambium layer overlies oedematous tissue. C Higher magnification of the cellular subepi- Endometrioid stromal sarcoma, thelial cambium layer. D The positive immunostain for desmin confirms the myoblastic differentiation. Note low grade the nuclear pleomorphism. Definition The clinical setting, the characteristic low sarcoma, only approximately 50 cases A sarcoma with an infiltrating pattern that power appearance, the absence of a have been reported {599}. They account- in its well differentiated form resembles cambium layer and striated cells and a ed for only 5 of 60 cases in the only large normal endometrial stromal cells. typically low mitotic index establish the series of vaginal smooth muscle tumours c o r rect diagnosis of a fibro e p i t h e l i a l {2879}. Histopathology polyp {2055,2067,2141}. Low grade endometrioid stromal sarco- Macroscopy mas have been rarely encountered in the Genetic susceptibility M a c ro s c o p i c a l l y, they are sometimes vagina and resemble their counterparts One instance of sarcoma botryoides has multilobulated and form masses from 3-5 in the endometrium. In two cases the been reported in a child with multiple cm. The sectioned surface has a pink- tumours appear to have arisen fro m congenital abnormalities and bilateral grey, "fish-flesh" appearance with scat- endometriosis {245}. Before concluding nephroblastomas suggesting a possible t e red foci of haemorrhage, myxoid that such a neoplasm is primary in the genetic defect {1965}. change or necrosis. The overlying vagina, an origin within the uterus should mucosa may be ulcerated. be excluded {633,1051,2226}. The term Prognosis and predictive factors undifferentiated vaginal sarcoma is pre- The prognosis of sarcoma botryoides in Histopathology ferred for the high grade lesions. the past was poor, but an 85% 3-year Histologically, they are identical to their survival rate has recently been achieved counterparts elsewhere. It may be diffi- Undifferentiated vaginal sarcoma with wide local excision and combination cult to predict the behaviour of some . Second in smooth muscle tumours. Currently, it is Definition long-term survivors of vaginal embryonal recommended that vaginal smooth mus- A sarcoma with an infiltrating pattern r h a b d o m y o s a rcoma have not been cle tumours that are larger than 3 cm in composed of small spindle-shaped cells reported to date. diameter and have 5 or more mitoses per lacking specific features. 10 high-power fields, moderate or Leiomyosarcoma marked cytological atypia and infiltrating Histopathology margins be regarded as leiomyosarcoma Un d i ff e r entiated vaginal sarcomas are Definition {2879}. An epithelioid variant with a myx- r a re, polypoid or diffusely infiltrating A malignant tumour composed of smooth oid stroma has also been described lesions. Spindle to stellate cells with muscle cells. {456}. As in the uterus, occasional sarco- scanty cytoplasm are arranged in sheet- mas arise from {1682}. like, fascicular or storiform patterns. The Epidemiology cells exhibit various degrees of nuclear Although leiomyosarcoma is the most Differential diagnosis pleomorphism and hyperchromasia. The common vaginal sarcoma in the adult L e i o m y o s a rcomas should be diff e re n t i a t- mitotic index is ³ 10 per 10 high power and the second most common vaginal ed from the benign condition of post- fields.

Mesenchymal tumours 303 Prognosis and predicitive factors Aetiology Death from re c u r rent or metastatic There are virtually no clues to the patho- tumour has occurred within 2 years of genesis of this group of tumours. Rare treatment in about 50% of patients {20, leiomyomas may recur in one or more 3236}. p regnancies suggesting horm o n e dependency {2501}.

Rare malignant mesenchymal Histopathology tumours Vaginal leiomyomas resemble their uter- ine counterparts. A case of bizarre (sym- R a re examples of malignant schwanno- plastic) leiomyoma has been described ma {633}, fibro s a rcoma {2160}, malig- {264}. nant fibrous {3078}, a n g i o s a rcoma {1804,2298,2931}, alveo- Histogenesis lar soft part sarcoma {402}, synovial sar- The histogenesis of smooth muscle coma {2095}, malignant peripheral nerve tumours is not clear, but myoepithelial sheath tumour {2226} and unclassifiable cells such as are found in smooth muscle s a rcoma {633} have all been described cells of venules or of the vaginal muscu- in the vagina, but they do not exhibit laris and myofibroblasts have all been unique clinical or morphological fea- implicated. tu re s . Prognosis and predictive factors Fig. 6.18 Genital rhabdomyoma. The tumour is Nearly all are treated by local excision composed of individual mature rhabdomyoblasts Benign mesenchymal {1682,2486,2523}. An occasional tumour, separated by abundant stroma. neoplasms especially if large, may recur {685,1682}.

Of the benign tumours only leiomyomas Genital rhabdomyoma Clinical features are relatively common. These tumours occur in middle age Definition women (range 30-48 years) and present ICD-O codes An uncommon benign tumour of the as a well defined, solitary mass with the Leiomyoma 8890/0 lower female genital tract showing skele- clinical appearance of a benign vaginal Genital rhabdomyoma 8905/0 tal muscle differentiation. polyp {1397}. Deep angiomyxoma 8841/1 Epidemiology Macroscopy Clinical features About 20 cases have been re p o rt e d Genital are solitary, Most benign tumours are asymptomatic, {1313,2812}. nodular or polypoid, ranging in size from but depending on their size and position they may cause pain, bleeding, dys- p a reunia and urinary or rectal symp- t o m s .

Leiomyoma

Definition A benign neoplasm composed of smooth muscle cells having a variable amount of fibrous stroma.

Epidemiology A p p roximately 300 cases of vaginal leiomyoma have been re p o rt e d . Although the age at presentation ranges from 19-72 years, they typically occur during reproductive life (mean age 44 years) {2879}. Leiomyomas of the vagina are not related to those of the uterus, either in frequency or in racial distribu- tion, the White to Black ratio for uterine and vaginal leiomyomas being 1:3 and Fig. 6.19 Genital rhabdomyoma. The tumour is composed of individual mature rhabdomyoblasts with cross 4:1 respectively {222}. striations in the cytoplasm and bland nuclei without mitotic activity.

304 Tumours of the vagina 1-11 cm. They may arise anywhere in the anorectal tracts. Imaging studies often marily surgical with close attention to vagina, and some protrude into the show the mass to be substantially larger margins. Approximately 30% of tumours lumen. The overlying mucosa is usually than clinically suspected. recur locally. intact since the tumour arises in the wall. The texture is rubbery and the sectioned Macroscopy Postoperative spindle cell nodule surface is grey and glassy. Macroscopically, the tumour is lobulated but poorly circumscribed due to finger- Definition Histopathology like extensions into the surrounding tis- A non-neoplastic localized lesion com- They are composed of mature, bland sue. The neoplasm is grey-pink or red- posed of closely packed pro l i f e r a t i n g rhabdomyoblasts that are oval or strap- tan and rubbery or gelatinous. spindle cells and capillaries simulating a shaped with obvious cross striations in the leiomyosarcoma. cytoplasm. Mitotic activity and nuclear Tumour spread and staging pleomorphism are absent. Abundant con- Deep angiomyxoma is a locally infiltrative Clinical features nective tissue stroma surrounds individual but non-metastasizing neoplasm that The lesion develops at the site of a recent muscle cells. Rhabdo- should not occurs for the most part during the rep r o- operation several weeks to several be confused with sarcoma botryoides. ductive years. At least two cases have months postoperatively {2861}. been reported within the vagina, an Prognosis and predictive factors uncommon site for this neoplasm {81, 496}. Histopathology No recurrences have been reported after The lesion is composed of closely complete local excision. Histopathology packed, mitotically active, spindle- The tumour is of low to moderate cellu- shaped mesenchymal cells and capillar- Deep angiomyxoma larity and is composed of small, uniform, ies often with an accompaniment of spindle-shaped to stellate cells with inflammatory cells. Definition poorly defined, pale eosinophilic cyto- A locally infiltrative tumour with a plasm and bland, often vesicular nuclei. Differential diagnosis predilection for the pelvic and perineal An abundant myxoid matrix contains a The history of a recent operation at the regions and a tendency for local recur- variable number of rounded, medium- same site serves to distinguish this lesion rence composed of fibroblasts, myofi- sized to large vessels that possess thick- f rom leiomyosarcoma. Postoperative broblasts and numerous, characteristi- ened focally hyalinized walls. A charac- spindle cell nodule may closely resemble cally thick-walled, blood vessels embed- teristic feature is the presence of loosely a leiomyosarcoma or other spindle cell ded in an abundant myxoid matrix. organized islands of myoid cells around sarcoma, but the history of a recent the larger nerve segments and vessels operation at the same site facilitates its Synonym {3086}. The neoplasm is positive for diagnosis. . desmin in almost all cases, where a s stains for S-100 protein are consistently Clinical features negative {1431,2082}. Most patients present with a large, slow- ly growing, painless mass in the pelviper- Prognosis and predictive factors ineal region that may give rise to pres- The treatment for this locally aggressive sure effects on the adjacent urogenital or but non-metastasizing neoplasm is pri-

Mesenchymal tumours 305 Mixed epithelial and mesenchymal S.G. Silverberg tumours

Definition Aetiology other lesion {2226,2714}. Imaging stud- Tumours in which both an epithelial and a The aetiology of the tumours in this group ies have not been reported for any of mesenchymal component can be histo- that are more often primary in the these lesions. logically identified as integral neoplastic endometrium, i.e. carcinosarcoma and components. adenosarcoma is discussed in the chap- Macroscopy ter on the uterine corpus of this publica- in their rare primary ICD-O codes tion. The aetiology of vaginal malignant vaginal manifestations are identical in Carcinosarcoma 8980/3 mixed tumour is essentially unknown. m a c roscopic appearance to their far Adenosarcoma 8933/3 more common endometrial counterparts. Malignant mixed tumour 8940/3 Carcinosarcoma Although primary vaginal tumours of this Benign mixed tumour 8940/0 sort are exophytic lesions, carcinosarco- Definition mas are more likely to be metastases Epidemiology A tumour with malignant epithelial and from the endometrium or elsewhere in the These mixed tumours are among the mesenchymal components. Before the female genital tract and may be deeper r a rest of vaginal primary tumours, diagnosis of a primary vaginal tumour is in the wall. which are themselves uncommon pri- made, extension from elsewhere in the m a ry tumours of the female genital female genital tract must be excluded. Tumour spread and staging tract. No mixed tumours were found Staging and spread of these malignant among 753 primary vaginal tumours Synonyms tumours are identical to those of primary compiled from ten re p o rts in the litera- Malignant müllerian mixed tumour, malig- vaginal carcinomas {2714} t u re {2714}. The U.S. National Cancer nant mesodermal mixed tumour, meta- Data Base Report on Cancer of the plastic carcinoma. Histopathology Vagina {577} includes only 25 "complex Primary vaginal carcinosarcoma is histo- mixed or stromal tumours" among 4,885 Clinical features logically identical to its endometrial coun- submitted cases of vaginal cancer. As These tumours present clinically as a terpart. A vaginal metastasis from an expected, there are no epidemiological palpable vaginal mass. Carci n o s a rc o - endometrial or other primary carcinosar- data available on mixed tumours mas usually bleed and may occur years coma may contain only the carcinoma- { 2 2 2 6 } . after therapeutic irradiation for some tous or rarely the sarcomatous compo- nent {1388,2692}.

Prognosis and predictive factors Most women with primary vaginal carci- n o s a rcomas have rapidly developed metastases and died.

Adenosarcoma

Definition A mixed tumour composed of a benign or atypical epithelial component of mül- lerian type and a malignant appearing mesenchymal component.

Clinical features Adenosarcoma presents clinically as a palpable vaginal mass.

Macroscopy Although primary vaginal adenosarcoma is typically an exophytic lesion, Fig. 6.20 Malignant mixed tumour of the vagina. The cellular tumour is composed of sheets of oval to spin- adenosarcomas are more likely to be dle-shaped cells with occasional gland-like formations and mitotic figures. metastases from the endometrium or

306 Tumours of the vagina elsewhere in the female genital tract and Benign mixed tumour may be deeper in the wall. Definition Histopathology A well circumscribed benign tumour his- Primary vaginal adenosarcoma is histo- tologically resembling the mixed tumour logically identical to its endometrial of salivary glands with a predominant c o u n t e r p a rt. Metastatic adenosarc o m a mesenchymal-appearing component generally consists of the sarcoma alone and epithelial cells of squamous or glan- {2692} dular type. A Prognosis and predictive factors Synonym Adenosarcomas of the vagina are not Spindle cell epithelioma. reported in enough numbers or detail to establish their prognosis. Clinical features The benign mixed tumour is usually Malignant mixed tumour asymptomatic, typically is a well-demar- resembling synovial sarcoma cated submucosal mass and has a predilection for the hymenal region {335, Definition 2714}. An extremely rare biphasic malignant It tends to occur in young to middle-aged tumour resembling synovial sarcoma and women, with a mean age of 40.5 in the B containing gland-like structures lined by largest series reported {335}. Fig. 6.21 Benign mixed tumour. A Low power mag- flattened epithelial-appearing cells and a nification shows circumscription without involve- highly cellular mesenchymal component. Macroscopy ment of the overlying squamous epithelium. B No t e There is no evidence of müllerian differ- Benign mixed tumours are circ u m- the squamous nest within a spindle cell prolifera- entiation. scribed, grey to white, soft to rubbery ti o n . masses, usually measuring from 1-6 cm Clinical features {335,2714} The two reported cases of mixed tumour Histogenesis resembling synovial sarcoma presented Histopathology The only benign vaginal tumour classi- as polypoid masses in the lateral fornix in The spindle cell component pred o m i n a t e s cally designated as a mixed tumour women of ages 24 and 33. histologically and lacks atypia or significant because of its histological re s e m- mitotic activity. Randomly interspersed are blance to the benign mixed tumour Histopathology nests of benign-appearing squamous cells () of salivary The mixed tumour resembling synovial and, less freq u e n t l y , glands lined by low glands has been renamed spindle cell sarcoma, as its name suggests, is com- cuboidal to columnar epithelium commonly epithelioma because of immunohisto- posed of gland-like structures lined by demonstrating squamous metaplasia. chemical and ultrastructural evidence round to flattened epithelial-appearing Hyaline globular aggregates of strom a l suggesting purely epithelial diff e re n t i a- cells embedded in a spindle cell matrix. matrix are also frequently seen. tion {335}. In one reported case electron micro- Unlike mixed tumours of salivary glands, scopic study suggested synovial-like dif- Immunoprofile these vaginal tumours show no immuno- ferentiation {2095}, whilst in another, a In an immunohistochemical study of a histochemical or ultrastructural features possible origin from mesonephric rests large series of cases, the spindle cells of myoepithelial cells {2717}. Origin from was proposed {2652}. w e re strongly keratin-immunore a c t i v e a primitive/progenitor cell population has in 90% cases {335}. They showed only been postulated {2717}. Prognosis and predictive factors minimal expression for smooth muscle Follow-up was too short to establish actin and were uniformly negative for Prognosis and predictive factors the clinical malignancy and survival S-100 protein, glial fibrillary acidic The benign mixed tumour has never rates of the two malignant mixed p rotein and factor VIII-related antigen metastasized in re p o rts of over fort y tumours resembling synovial sarc o m a {335,2717}. The tumours coexpre s s e d cases; however, local recurrences have re p o rted in the literature . CD34, CD99 and Bcl-2 {2717}. been noted.

Mixed epithelial and mesenchymal tumours 307 R. Vang Melanotic, neuroectodermal, lymphoid F.A. Tavassoli and secondary tumours E.S. Andersen

Melanocytic tumours tions are in the lower third of the vagina Clinical features and on the anterior vaginal wall. Though rare, both common and cellular Definition variants of blue naevus have been A tumour composed of melanocytes, Macroscopy reported in the vagina {2400,2929}. The either benign or malignant. The lesions are pigmented and usually common variant typically presents as a 2-3 cm in size. blue-black macule and the cellular vari- ICD-O codes ant as a nodule. Malignant melanoma 8720/3 Histopathology Blue naevus 8780/0 The lesions are invasive and may display Histopathology Melanocytic naevus 8720/0 ulceration. Most have a lentiginous grow t h Classic blue naevi contain melanocytes pa t t e r n, but junctional nests can be seen. with elongated dendritic processes and Malignant melanoma In-situ or pagetoid growth is not typical. heavy cytoplasmic pigmentation. Cellular The cells are epithelioid or spindle-shaped Definition and may contain melanin pigment. There is A tumour composed of malignant brisk mitotic activity. Tumour cells expres s melanocytes. S-100 protein, melan A and HMB-45.

Epidemiology Differential diagnosis Malignant melanoma is a rare but very As "atypical" or dysplastic melanocytic aggressive tumour of the vagina. Patients lesions of the vagina have not been evalu- have an average age of 60 years and ated, histological separation of "borde r l i n e " most are White {492}. melanocytic lesions from melanoma is not always possible. Nests of epithelioid cells Clinical features raise the possibility of a poorly diffe re n t i a t - A They typically present with vaginal bleed- ed carcinoma. Spindle cell diffe re n t i a t i o n ing, and some may have inguinal lym- may create confusion with sarco m a s . phadenopathy. The more common loca- Prognostic and predictive factors Clinical criteria Patients have been treated by a combi- nation of surgery, radiation and chemo- therapy. The prognosis is poor with a 5-year survival rate of 21% and a mean survival time of 15 months {314}. B Histopathological criteria Assessment of Clark levels, as is done for of skin, is not possible given the lack of normal cutaneous anatomical landmarks. Most tumours have a significant thickness, but even a thin melanoma does not necessarily por - tend a favourable prognosis. One study found that mitotic activity correlates bet- ter with the clinical outcome than the C depth of invasion {314}. Fig. 6.23 Melanoma of the vagina. A Note the prominent junctional component. B The tumour Blue naevus cells are epithelioid with abundant eosinophilic cytoplasm, large pleomorphic nuclei, prominent Definition nucleoli, intranuclear inclusions and mitotic fig- Fig. 6.22 Melanoma of the lower anterior vaginal wall. A proliferation of subepithelial dendritic ures. C Immunostain shows diffuse, strong expres- Note the large, polypoid heavily pigmented tumour. melanocytes. sion for melan A.

308 Tumours of the vagina A B Fig. 6.24 Yolk sac tumour. A The tumour has a labryinthine pattern with occasional Schiller-Duvall bodies. B Papillary cores and labryinthine structures are lined by primitive cuboidal cells with cytoplasmic vacuolization and rare hyaline globules.

variants have a biphasic composition ICD-O code 9071/3 Ewing tumour 9260/3 with areas similar to common blue nae- vus admixed with round nodules. The Synonym Clinical features cells are arranged in nests and short fas- Endodermal sinus tumour. Peripheral primitive neuro e c t o d e rm a l cicles with a whorled pattern and are tumour/Ewing tumour (PNET/ET) is rare plump and spindle-shaped with oval Clinical features within the vagina {3002}. A reported case bland nuclei and pale cytoplasm. Patients are usually under 3 years of age. occurred in a 35-year-old woman who Vaginal bleeding and discharge are the presented with a vaginal mass. Differential diagnosis most common symptoms. Serum levels The common variant should not pose a of alpha-fetoprotein may be elevated. A Histopathology diagnostic problem. The cellular variant polypoid friable mass is seen on clinical Histological features are similar to may cause confusion with melanoma and examination with a mean size of 3 cm. PNET/ET in non-vaginal sites. Typically, smooth muscle tumours. Nuclear atypia PNET/ET grows as a diffuse sheet of uni- and numerous mitotic figures would Histopathology form small cells with scant pale cyto- favour melanoma. Well defined interlac- Vaginal cases resemble their ovarian plasm and an intermediate to high ing fascicles, large thick-walled blood counterparts. nuclear to cytoplasmic ratio. The nuclei vessels, immunohistochemical positivity are round with evenly dispersed chro- for muscle markers and negativity for Differential diagnosis matin. Mitotic figures may be numerous, S-100 protein should assist in making the Although sarcoma botryoides may be and rosettes may be seen. diagnosis of a smooth muscle tumour. simulated clinically, the histological fea- tures resolve any confusion. Clear cell Immunoprofile Melanocytic naevus and endometrioid carcinomas may cre- Expression of CD99 would be expected ate difficulty in histological separation. in almost all cases. Definition Melanocytic nevi are defined as prolifer- Prognosis and predictive factors Differential diagnosis ation of nests of naevus cells. Combined surgery and chemotherapy PNET/ET should not be mistaken for may provide a favourable outcome. A rhabdomyosarcoma, non-Hodgkin lym- Clinical features disease-free survival of up to 23 years is phoma (NHL), melanoma, small cell car- Melanocytic nevi of the vagina are possible {557}. cinoma or endometrial stromal sarcoma thought to be similar to their counterparts because of differences in prognosis and in the skin {1539}. Peripheral primitive neuroectodermal treatment. A broad immunohistochemical tumour / Ewing tumour panel and, if need be, molecular studies, Yolk sac tumour performed on paraffin-embedded tissue Definition should assist in making the correct diag- Definition Tumours of uncertain lineage within the nosis. A primitive malignant germ cell tumour small round blue cell family of tumours. characterized by a variety of distinctive Molecular genetics histological patterns, some of which ICD-O code Identification of the EWS/FLI1 fusion tran- recapitulate phases in the development Peripheral primitive script derived from the t(11;22)(q24;q12) of the normal yolk sac. neuroectodermal tumour / 9364/3 c h romosomal translocation by the

Melanotic, neuroectodermal, lymphoid and secondary tumours 309 Dermoid cyst Lymphoid and haematopoetic tumours Definition A cystic tumour composed of more than Definition one germ cell layer in which all elements Tumours of the lymphoid and haematopo- are mature. etic systems as well as secondary tumours of the vagina. ICD-O code Dermoid cyst 9084/0 Lymphoma Mature cystic 9080/0 Definition Fig. 6.25 Peripheral primitive neuroectodermal Synonym Tumours with lymphoid diff e re n t i a t i o n tumour. Note the sheets of small to medium sized Mature cystic teratoma. arising as either primary (localized) or cells with round, pale nuclei, minimal cytoplasm and high nuclear to cytoplasmic ratios. secondary (disseminated) disease. Macroscopy and histopathology These resemble the same tumour in the Clinical features ovary. Lymphomas of the vagina are predomi- reverse transcriptase-polymerase chain nantly of the non-Hodgkin’s type {3001}. reaction and Southern blot hybridization Adenomatoid tumour Patients with primary NHL have a mean would confirm the diagnosis. age of 42 years, usually present with ICD-O code 9054/0 vaginal bleeding and have a mass on Prognosis and predictive factors clinical examination. Patients with sec- The experience with PNET/ET of the A single case occurring in a 47-year-old ondary NHL have a mean age of 65 vagina is limited, but patients with local- woman has been reported {1697}. years, present with vaginal bleeding and ized tumours in soft tissue sites can usually have a history of NHL. potentially be cured with a combination of surgery, chemotherapy and radiation Histopathology therapy. Almost all NHLs primary in the vagina a re diffuse large B-cell lymphomas

Table 6.03 Immunohistochemical and cytogenetic profile of various small cell tumours of the vagina.*

Immunohistochemical Peripheral primitive Rhabdomyosarcoma B-cell Melanoma Small cell Endometrial or molecular markers neuroectodermal non-Hodgkin carcinoma stromal tumour/Ewing tumour lymphoma sarcoma

Cytokeratin +/- +/- - - + +/-

Muscle specific actin/ desmin - + -- - +/-

Chromogranin/ synaptophysin +/- - -- +/- -

S-100 protein +/- - - + - -

HMB-45 - - - + - -

Leukocyte common antigen/ CD20 - - + - --

CD10 - - +/- - - +

CD99 + +/- +/- - --

t(11;22) + - -- --

t(2;13)/ t(1;13) - +/- -- --

Monoclonal immunoglobulin heavy chain gene - - +/- - -- rearrangement

Key: +/-, variable rate of positivity; *, Not all markers have been thoroughly tested for each tumour, but expected results are listed.

310 Tumours of the vagina g rowing in sheets. Some may have scle- Leukaemia or immunohistochemical stains for rosis. The neoplastic cells are large with myeloproxidase, CD68 and CD43 will round nuclei, vesicular chromatin and Definition establish the diagnosis in almost all nucleoli. Secondary cases are usually A malignant haematopoetic neoplasm cases {2099}. d i ffuse large B-cell lymphomas and are that may be primary or secondary. histologically similar to the primary Prognosis and predictive factors cases. Synonym Granulocytic sarcoma of the vagina Granulocytic sarcoma. appears to behave in an aggre s s i v e Immunoprofile fashion. Although experience is limited, Almost all NHLs of the vagina (primary or Epidemiology the few reported granulocytic sarcomas secondary) are of B-cell lineage and typ- Vaginal involvement by leukaemia may of the vagina have also been treated with ically express CD20. either be primary or secondary; however, chemotherapy or radiation. the latter is much more common {428}. Differential diagnosis The main lesions in the differential diag- Clinical features Secondary tumours nosis of NHL include granulocytic sarco- Leukaemia of the vagina is rare but is ma and other haematological malignan- usually of the myeloid type (granulocytic Definition cies, carcinoma, melanoma and small sarcoma or "chloroma") {2099}. Patients Tumours of the vagina that originate out- round blue cell tumours such as rhab- a re elderly, have a mass on clinical side the vagina. domyosarcoma. Knowledge of the age, examination and may have other evi- previous history of NHL or leukaemia, dence of acute myeloid leukaemia. Incidence and origin and the immunoprofile (keratin, CD20, Metastatic tumours are more freq u e n t CD3, CD43, myeloperoxidase, S-100 Histopathology than primary malignant tumours of the protein, desmin and other muscle mark- A series of primary granulocytic sarco- vagina. Tumours may spread by direc t ers) should help establish the correct mas of the female genital tract including extension, most commonly from the cervix diagnosis. 3 cases of the vagina was re p o rt e d or vulva, vascular and lymphatic dissemi- {2099}. Granulocytic sarcomas are usu- nation or by implantation. Metastatic ade- Somatic genetics ally composed of cells with finely dis- no c a r cinomas originate from the endo- Southern blot analysis and polymerase persed nuclear chromatin and abundant metrium, colon, rectum and, more rarel y , chain reaction (PCR) can demonstrate cytoplasm that may be deeply eosino- the breast. Transitional cell carci n o m a monoclonal immunoglobulin heavy chain philic. The identification of eosinophilic metastatic from the urethra and the blad- gene rearrangements in vaginal NHL. In- myelocytes is helpful in establishing the der and renal cell carcinomas have been situ hybridization has not confirmed the diagnosis; however, they are not always rep o r ted. In the past vaginal metastases presence of human papillomavirus DNA present. The tumours are positive for we r e rep o r ted in up to 50% of cases of or Epstein-Barr virus (EBV) RNA {2999}; chloroacetate esterase. uterine choriocarci n o m a . however, EBV DNA has been found by PCR {2718}. Immunoprofile Clinical features Granulocytic sarcomas express lyso- The primary tumour is often clinically evi- Prognosis and predictive factors zyme, myeloperoxidase, CD43 and dent or has previously been treated. The Vaginal NHL is usually treated by CD68. Staining for CD45 may be seen, most significant symptom is abnormal chemotherapy and radiation. The deter- but the tumour cells are negative for vaginal bleeding. Vaginal cytology may mination of the Ann Arbor stage is prog- CD20 and CD3. aid detection. A biopsy is contraindicat- nostically important for vaginal NHL. ed in metastatic trophoblastic disease Patients with low stage tumours (stages Differential diagnosis due to the risk of excessive bleeding. IE and IIE) have a longer disease-free The most important differential diagnosis survival than those with high-stage dis- is malignant lymphoma. Enzyme histo- ease have (stages IIIE and IV). chemical stains for chloracetate esterase

Melanotic, neuroectodermal, lymphoid and secondary tumours 311

Top View