Keywords
vaginal cancer - vaginal sarcoma - pelvic radiotherapy - postcoital bleeding - gynecologic
hemorrhage
Palabras Clave
cancro vaginal - sarcoma vaginal - radioterapia pélvica - coitorragia - hemorragia
ginecológica
Introduction
The primary vaginal cancer comprises approximately only 3% of all malignant neoplasms
of the female genital tract.[1] This type of cancer is rare, and a metastatic disease or local extension from adjacent
gynecologic structures to the vagina is not uncommon.[2] Consequently, it must be excluded before assuming a primary neoplasm.
The most common clinical presentation of vaginal cancer is vaginal bleeding, typically
postcoital or postmenopausal.[3]
[4] Many women are asymptomatic. A vaginal mass may also be noted by the patient.[3]
[4] Other potential symptoms are related to local extension of the disease. The posterior
wall of the upper one-third of the vagina is the most common site of primary vaginal
carcinoma.[4] The lesion may appear as a mass, a plaque or an ulcer.
Leiomyosarcomas, endometrial stromal sarcomas, malignant mixed Müllerian tumors and
rhabdomyosarcomas are the major types of primary vaginal sarcomas.[4] They represent less than 3% of all vaginal cancers. Less than 50 cases of vaginal
leiomyosarcoma are reported in the literature. Still rare, the most common type of
leiomyosarcoma is the embryonal rhabdomyosarcoma.[5]
Vaginal tumors may invade locally and disseminate by several routes: direct extension
to pelvic soft tissue structures, lymphatic spread and hematogenous dissemination,
depending on the stage and histological type. The most important variable affecting
the prognosis is the stage at the time of presentation. The global poor survival rates
(even lower in sarcomas) may reflect the higher proportion of vaginal tumors initially
diagnosed at an advanced stage, and the potential for treatment complications that
prevents aggressive therapy.[4]
[6]
Case Description
A 53-year-old premenopausal woman presented to the urgent care department with severe
vaginal bleeding and a history of postcoital and intermenstrual bleeding over the
previous two months. In her gynecological/obstetrical history, she had two pregnancies
— one vaginal delivery and one ectopic, for which she underwent a salpingectomy at
laparotomy. She was known to have no relevant medical history or concerns. Her father
and mother died of lung and breast cancer, respectively.
At the physical examination, the patient weighed 66 Kg, appeared pale and lethargic,
but otherwise well. The abdominal examination was normal. Upon speculum examination,
an ulcerative and necrotic lesion was noted in the upper two thirds of the vagina,
raising suspicion of neoplasia and, consequently, a biopsy was performed. The bimanual
examination was painful, and the lesion was noted to be irregular, but it was not
obliterating the fornices or reaching the cervix; the corpus and cervix of the uterus
were mobile, not enlarged and no adnexal masses, inguinal or parametrial lymphadenopathies
were palpable. Digital rectal examination found a normotonic sphincter and free rectal
ampulla.
Foi aconselhado por um revisor colocar uma imagem da Ressonância Magnética original
documentando a lesão. Já pedi para levantar o processo para a tirar mas dará tempo
para acrescentar a imagem? Deve estar pronta nesta semana. The lesion had well defined
limits, and it was reaching the bladder and cervix without invasion, without ureteric
dilation, para-vaginal or rectal involvement ([Fig. 1]). Internal and external iliac lymphadenopathy was noted bilaterally (shortly after,
guided MR biopsy-proven reactive). The uterus was normal in size, with a regular contour
and 4 mm endometrium. The remaining thoracoabdominal exam was unremarkable.
Fig. 1 Lesion limits, reaching the bladder and cervix.
The histological analysis of the tumor sample showed epithelioid cells with necrotic
areas and high levels of mitosis— most likely a primary vaginal leiomyosarcoma and
less likely a mixed Müllerian tumor—after immunohistochemical evaluation (CD31 negative,
CD34 negative, CD10 occasionally positive, AE1/AE3 negative, AML positive, vimentin-positive,
desmine-negative), highlighting a probable muscular neoplasia ([Fig. 2A] and [2B]).
Fig. 2 (A and B) Histology - Epithelioid cells with necrotic areas and high mitotic rate, most likely
a leiomyosarcoma.
After multidisciplinary team (MDT) review at an oncology institute, it was agreed
to offer initial treatment with RT, then subsequent assessment to consider the possibility
of pelvic exenterative surgery with intraoperative radiation therapy. It was agreed
that management will increase the possibilities of cure, and not primary surgical
resection, which also are amenable.
Within a week of the MDT review and prior to her first session of RT, the patient
developed urinary frequency, constipation and uncontrolled pelvic pain despite analgesia.
Upon examination, there were no recent changes, except for paracolpos infiltration
on digital rectal examination. She commenced RT (total 50Gy) of the whole pelvis and
vagina with external radiation delivered at 2Gy/day, IMRT (Intensity-Modulated Radiation
Therapy) 5 times/week with diary portal vision during the first week, and after then,
once per week ([Fig. 3]). Seven days later, the pelvic pain and constipation were controlled.
Fig. 3 (A and B) Dosimetric plan and dose-volume histogram.
After two weeks of RT, 20 Gy had been administered and the patient reported an improvement
in her appetite, lethargy and intermenstrual bleeding, despite the diagnosis of microcytic
anemia of 8,1 g/dL, then managed with transfusion. The gynecological examination revealed
large tumoral necrosis, and the patient felt able to manage on less painkillers and
was commenced on oral doxycycline.
During the last week of RT, the patient developed lethargy and anorexia. No changes
were found during the examination at this time, other than her weight had dropped
by 5 kg to 61 Kg. The serum biochemistry revealed hypomagnesemia and a borderline
potassium deficiency, which was treated with oral supplements. Finally, she completed
50 Gy of RT with average global state; maintaining weight (61 Kg) and examination
findings.
Two days later, she complained of epigastric/right hypochondrium pain and bowel subocclusion
semiology, with worsening anorexia. She had slightly painful deep palpation of the
right hypochondrium and epigastrium (suspected hepatomegaly) without signs of peritoneal
irritation. She was tachycardic (130 bpm), but the remaining vitals were normal. In
the thoracic X-ray, pulmonary metastasis was revealed (micro and macronodules of irregular
limits) and an abdominal X-ray confirmed subocclusion. The progression of the disease
was also documented in the serum samples, which revealed thrombocytopenia of 47,000/uL,
hyponatremia, hypomagnesemia and elevated liver parameters (aspartate transaminase
[AST]/alanine transaminase [ALT] double the upper normal limit (UNL), total bilirubin
1.5 x UNL, alkaline phosphatase 10 x UNL, lactate dehydrogenase 6.8 x UNL), raising
concern of probable hepatic/peritoneal metastasis.
The patient was admitted for supportive care, under a nil-by-mouth regimen, and with
fluid resuscitation. During the subsequent MDT review, a decision was made to refer
her care to palliative care. The patient passed away on the following day.
Discussion
Vaginal sarcoma is a very rare oncology malignancy, within the already infrequent
vaginal cancer category.
The staging is clinical, based upon findings from physical examination cystoscopy,
proctoscopy, and chest and skeletal radiography.[6]
[8] An MRI can assist in determining the primary vaginal tumor size and local extent.
Vaginal tumors are generally best seen on T2 imaging.[9] Despite the fact that the majority of available evidence is for squamous cell carcinoma
and adenocarcinoma, the positron emission tomography–computed tomography (PET-CT)
value appears to be useful to address metastization, mainly in advanced stages.[10]
[11] The guided biopsy performed may have a role in cancer dissemination, but this appear
to be very unlikely. In the first place, the lymphadenopathies were reactive (even
in pathologic revision). Furthermore, we only found studies justifying this concern
in uterine cancers, when morcelation is used. The International Federation of Gynecology
and Obstetrics (FIGO) and the Tumor, Nodes, Metastasis (TNM) classification recommend
a clinical staging system for vaginal cancer.[6]
With regard to global vaginal cancer, 37% of the patients are diagnosed at stage II,
and 37% at stages III or IV.[8] In the case of sarcomas, the outcome is even worse.[4]
[6]
[8] In this case, due to the already advanced stage of the disease, the patients are
often not candidates for surgery. Given the relatively poor outcomes with treatment
using RT alone, chemoradiation is often administered, rather than RT. This is largely
based on an extrapolation of the improved outcomes with chemoradiation for the treatment
of locally advanced cervical cancer, but studies in vaginal cancer show that locoregional
control rates are high after chemoradiotherapy, and radiation-related long-term side
effects do not seem worse compared with RT alone.[12]
[13]
[14] However, given the lack of high-quality data to inform the benefits of chemoradiation,
RT is a reasonable alternative, particularly for patients who are not candidates for
cisplatin-based chemotherapy, for whatever reason.[4] The data to support this approach specifically for vaginal cancer is low-quality
and largely limited to small retrospective series.[12]
[13]
[14]
[15]
[16] The leiomyosarcoma treatment (more rare) is often extrapolated for squamous cell
carcinoma. In the case herein described, the goal was to control the symptoms and
reduce the tumor, allowing a possible curative pelvic exenterative surgery with less
morbidity. Surgery as a primary treatment modality is associated with less favorable
outcomes, with it being typically difficult to obtain negative margins in women with
large or extensive lesions without compromise of the bladder or rectum.[4] Neoadjuvant therapy is largely experimental.[4]
A total radiation dose of at least 70 to 75 Gy is generally recommended, with 45 to
50 Gy delivered with external beam radiation, and the additional radiation administered
with intracavitary or interstitial brachytherapy radiation, depending on the thickness
of the primary tumor. The external radiation should include the pelvic lymph nodes,
vaginal tumor with a margin, vagina, and paravaginal tissues and inguinal lymph nodes,
if the vaginal tumor is in the lower half of the vaginal canal. Brachytherapy radiation
should immediately follow the completion of external radiation.[4]
[17]
The prognosis for patients with this malignancy has improved with the use of multimodal
therapy, including surgery and chemotherapy. If chosen, the surgical approach requires
a radical hysterectomy, upper or total vaginectomy, and bilateral pelvic lymphadenectomy.
Patients in the early stages of vaginal cancer appear to have the best outcomes when
treated this way.[2]
[3]
[4] For some patients, radiotherapy (RT) alone could be an adequate treatment, particularly
important with concomitant brachytherapy. Patients with more advanced disease are
often not candidates for surgery. Given the relatively poor outcomes with treatment
using RT alone, chemoradiation is often administered, rather than RT. However, the
treatment options evidence a lack of high-quality data and there are no randomized
trials defining the treatment for vaginal cancer, given its rarity.[4]
[6] Instead, the treatment management is extrapolated from cervical or anal cancers
and should be individualized depending upon the location, size and clinical stage
of the tumor.[7] In addition, the treatment must consider the local anatomic constraints and psychosexual
issues.
There is no treatment defined for vaginal sarcoma. Usually is surgery, as the most
of others sites. For advanced gynecologic sarcomas, until now, and not possible to
control by surgery (not resection possible), the management can be considered palliative,
what include radiotherapy with or without chemotherapy. In the present case, the metastasis
found and worse evolution are in accordance with advanced stage of the disease. This
kind of evolution is common in cervix neoplasia in advanced stage. The authors tried
to treat by radiotherapy aiming to increase the possibilities for successfull surgery
with less comorbidity, which was proven not suitable for this neoplasia.
Conclusion
Vaginal sarcoma is a rare malignancy and the treatment plan should be individualized
depending upon the location, size, and clinical stage of the tumor. For patients with
more advanced disease, chemoradiation is suggested, rather than RT.[4]
[12]
In this case, with a poor prognosis, the expected evolution is minimal and the primary
best treatment is still controversial. The current evidence on sarcomas is poor and
related to case series or case-reports, usually with bad evolution. Nevertheless,
a chemoradiation scheme or primary surgical resection might have a better outcome
in terms of survival (although with more side effects), even with high morbidity and
worst psychosocial impact, in the case of premenopausal women. Thus, these treatments
should be considered in the future, as they seem to be the main recommendation of
last case series available.[18]
