Keywords
anal cancer - pregnancy - squamous cell carcinoma - cervical dysplasia - papillomavirus
infection
Introduction
Cancer in pregnancy is defined as a malignant neoplasm that is diagnosed during pregnancy
and up to 1 year postpartum. It is an infrequent scenario, with the frequency corresponding
to 0.1% of pregnancies in the United States. The most frequent cancers in pregnant
women are cervical cancer, in the first place, followed by breast cancer, then, with
variable frequency, hematological neoplasms, melanoma, thyroid, ovarian, and colorectal.[1]
[2]
Anal cancer (AC) is very rare in the general population, representing less than 1%
and 3% of all new diagnoses of gastrointestinal cancer and tumors, respectively.[3] The incidence is 1.5 times higher in women than in men, and about 54% occur in people
over 65 years of age.[4] In Europe, the incidence rate between 25 and 44 years of age is 3.9 per 100,000
per year,[4] while in the United States, it is estimated that 9,760 new cases will arise in 2023.[5] No epidemiological data published in Chile were found. To date, there are no reports
of cases of AC in pregnant women published nationally or internationally.
Among the most frequent symptoms of AC, there is bleeding (45%), followed by pain,
sensation of rectal mass, ulcer that does not heal, discharge, fistula, and pruritus,
which are non-specific symptoms and in 70 to 80% of cases are initially diagnosed
as benign conditions.[3]
[4] Pain on defecation, anal discharge, changes in bowel habits, and incontinence suggest
larger and more advanced lesions.[4] Many of these symptoms are present in normal pregnancy, which can make diagnosis
difficult.[6]
Its management should be individualized and based on the principles of managing the
general population. International guidelines make explicit the need for counseling
regarding fertility problems secondary to treatment.[2]
[3]
[7] The usual management of chemotherapy (QT) and radiotherapy (RT) followed by surgical
treatment requires a multidimensional approach according to the type of cancer, tumor
stage, and gestational age.[1]
[3]
[7] This management achieves a long-term survival of 80 to 90% of patients; however,
it cannot be performed during pregnancy since pelvic radiation is contraindicated.[1] The decision of the appropriate moment to start treatment must be informed and agreed
upon between the pregnant patient, gynecologists, and oncologists.
It is of special interest to publicize this clinical case as it is an extremely unusual
scenario that falls outside the general framework of clinical guidelines. In addition,
there are no cases published nationally or internationally.
Clinical Case
We describe the case of a 34-year-old woman undergoing a 24-week pregnancy with a
history of uterine cervical pathology associated with human papillomavirus (HPV) that
required surgical treatment with a cervical cone in 2022 due to intraepithelial neoplasia
(IEN) III.
She presented with an 8-month history of proctalgia, volume increase, intermittent
rectal bleeding, and anal discharge. The physical examination revealed the presence
of an ulcerated tumor in the anus, 4 cm in diameter, located in the right posterior
quadrant, and associated with thickening and pain on mobilization of the anal sphincter.
The pathology study reported the presence of well-differentiated squamous cell carcinoma
(SCC) with a positive p16 marker.
Human immunodeficiency virus (HIV) was ruled out. Staging was performed with magnetic
resonance imaging (MRI) of the abdomen and pelvis and computed tomography (CT) of
the chest. Eccentric parietal thickening of the anal canal was identified with compromise
of the external and internal sphincters. Extension toward the pectineal line, levator
ani muscle, and posterior wall of the lower third of the vagina. No regional adenopathies
or distant lesions ([Fig. 1]).
Fig. 1 Evolution of magnetic resonance imaging (MRI) of pelvis in T2-weighted sequence at
the time of diagnosis (A, B), after cesarean section (C, D), and control at 3 (E, F) and 5 months (G,H) after chemoradiotherapy .Notes: A, axial section, tumor involvement of the left internal anal sphincter (IAS) and external
anal sphincter (EAS) (arrow). B, coronal section, tumor involvement of the right IAS and the levator ani muscle (arrow). C and D, axial and coronal sections with tumor progression, greater involvement of the IAS,
EAS, and puborectalis muscle (arrow). Axial (E) and coronal (F) sections with absence of foci of tumor thickening of the anal canal (*). G and H, axial and coronal sections, right posterolateral neoplastic thickening of the upper
third of the anal canal (arrow), not visible in previous control (E, F) and involvement of the right levator ani muscle (^).
With a diagnosis of stage IIIB anal SCC (cT4 N0 M0) (AJCC 2018), the case was discussed
with a multidisciplinary team made up of a medical oncologist, gynecologists, coloproctologists,
and the patient defined treatment with QT to allow disease control while waiting for
fetal maturation.
She received 3 cycles of paclitaxel 280 mg ev + carboplatin 800 mg ev. In addition,
intravenous betamethasone for fetal lung maturation at the completion of chemotherapy.
During QT, the patient had occasional rectal bleeding, but no adverse hematological
effects. Once treatment was completed, she was scheduled for a cesarean section on
the 35th week of gestation, giving birth to a healthy newborn (2,170 grams and 42.5 cm).
In the postpartum tumor evaluation, the CT evidenced growth of the anal neoplasia
without distant spread, and MRI of the pelvis confirmed slight growth ([Fig. 1]). In this context, breastfeeding was suspended, and QT (cisplatin 90 mg IV + capecitabine
1150 mg po, 2 cycles) and RT (54 Gy to the primary tumor and 45 Gy to regional lymph
nodes) were started.
It evolved with persistent actinic proctitis and perineal dermatitis. The patient
required hospitalization for management with corticosteroids and topical Vaseline,
achieving clinical improvement and adequate pain management with a buprenorphine patch.
At 3 months post RT, the patient had complete clinical and imaging regression ([Fig. 1]). Subsequently, she evolved with a reappearance of proctorrhagia, proctalgia, and
gas and bowel incontinence. The physical examination revealed a severe anal stenosis
that did not allow rectal examination ([Fig. 2]). A sigmoid loop colostomy was performed, which relieved the symptoms, and a new
biopsy sample was taken to confirm tumor regrowth.
Fig. 2 Above: severe actinic stenosis of the anal canal. Biopsies of tumor regrowth taken
from the anal canal in the right posterior quadrant (arrow). Below: evolution of anal stenosis due to tumor regrowth 6 months after chemoradiotherapy.
The patient completed 5 cycles of nivolumab, and an abdominoperineal amputation was
performed. The abdominal approach was laparoscopic, and the perineal approach was
in forced lithotomy, with the “extralevator” technique. Due to compromise of the posterior
wall of the vagina, she required partial resection of it ([Fig. 3]). Bio-A mesh was installed on the pelvic floor, and perineorrhaphy was performed
in three planes, leaving Blake drains through the abdominal and perineal routes. The
patient evolved favorably, being discharged on the 3rd day with a perineal drain that was removed after a week. The pathology report confirmed
the presence of poorly differentiated SCC, stage IIIB (pT4N0), with negative surgical
margins.
Fig. 3 Surgical piece for extralevator abdominoperineal resection. Height of the levator
ani muscle (black arrow), tumor extension to the right and anterior with vaginal compromise (asterisks), with intact cylindrical mesorectum.
Discussion
Malignant pathology in pregnant women is a rare entity.[2] Regarding anal SCC and its synchrony with pregnancy, there are no cases published
in the international literature to date. The tumors do not have repercussions on pregnancy,
the rate of abortions or premature births is the same of a pregnancy without cancer.
The presence of fetal involvement has been described in cases of synchronous melanoma.[1] Anal SCC frequently presents with proctorrhagia (45%), proctalgia (30%), and sensation
of perianal mass (30%), symptoms compatible with what the described patient presented.[3]
[4]
A risk factor associated with this neoplasia is the presence of cervical pathology
associated with HPV, as in the case presented. There is convincing evidence showing
the relationship between HPV 16 and 18 infection and the development of anal SCC.[4]
[6] Other known risk factors are anal intercourse, the presence of HIV, smoking, and
other sexually transmitted infections.[6] The patient did not present immunization against HPV.
For decades, the most effective treatment has been chemoradiotherapy for both localized
stages (T1–2N0) and locally advanced disease (T3–4 and/or N + ), with good long-term
results.[3]
[6]
[8]
[9] For T2-to-3 N0 patients, the overall 5-year survival reaches 82%, while disease-free
survival reaches 72%. T4-N0 patients at 5 years have somewhat lower overall and disease-free
survival (57% and 50%, respectively).[4]
[9] Recurrences vary between 20 and 44% at 5 years of follow-up and are especially frequent
in the advanced cancer group.[8]
In this case, the diagnosis was made of an advanced disease with involvement of the
sphincter complex, pelvic floor, and posterior wall of the vagina, with a good response
initially, but with early recurrence.
In cases of poor response to chemoradiotherapy or recurrence, the treatment of choice
is surgical resection. In this case, a laparoscopic abdominoperineal resection was
performed with wide resection of the pelvic floor, which was reinforced with a resorbable
synthetic mesh (Bio-A) used safely in laparotomy closures by anterior approach,[10] and with partial resection of the posterior wall from the vagina.
Conclusion
Anal cancer concurrent with pregnancy is an extremely rare scenario. The importance
of early detection is emphasized in this context, especially in patients with a history
of NIE and HPV. Performing anal screening becomes an essential pillar for the early
identification of preneoplastic lesions and, therefore, of possible cases of anal
SCC.
Pregnancy adds a complex ethical challenge to the equation, requiring the collaboration
of a multidisciplinary team for decision-making that considers both the mother's health,
her desire for future fertility, and the health of the fetus. The case presented underlines
the need to address these situations comprehensively and carefully, showing that the
collaboration between oncologists, gynecologists, and coloproctologists is crucial
to define an appropriate treatment approach.
