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12 Anal C ance r
12.4 Case 2
A 39-year-old homosexual male presented with anal discomfort, intermittent bright
red blood per rectum, tenesmus, and a palpable mass inside the anal verge. He had
had unprotected anal intercourse with multiple partners over the preceding 10 years.
Examination under anesthesia (EUA) revealed a hard pedunculated mass below
the dentate line. Multiple biopsies were taken and sent for urgent histopathology.
Further examination demonstrated enlarged, hard, non-tender lymph nodes in the
left inguinal canal.
Endoanal ultrasound was performed for evaluation of tumor size and extension
and infi ltration of the sphincter muscle complex. It confi rmed a 4 × 2 cm lesion
invading the anal sphincter (T3N1). Biopsies demonstrated invasive squamous cell
carcinoma. He was found to have HPV p16 infection. P63 positivity confi rmed the
squamous origin of the tumor (Fig. 12.2a–c ). Staging CT of thorax, abdomen, and
pelvis was negative for distant metastases. Serology was positive for human immunodefi ciency virus (HIV). CD4 count was 620.
269
Fig. 12.2 ( a ) Invasive squamous cell carcinoma . ( b ) Immunohistochemistry with p16 showing
diffuse staining in invasive squamous cell carcinoma indicating association with high-risk HPV. ( c )
Immunohistochemistry positivity with p63 nuclear stain confi rming “squamous” origin of the
carcinoma
270
A.M. Hogan et al.
Chemoradiotherapy and antiretroviral therapy were commenced. EUA was
performed 12 weeks following completion of systemic treatment, and there was no
visible or palpable lesion. Biopsies were taken and did not demonstrate any residual
tumor cells. The patient was considered to have undergone a complete pathological
response and was enrolled on a surveillance program to ensure early detection in the
case of recurrent disease.
12.4.1 Learning Points
• The relation between anal cancer and receptive anal intercourse is similar in both
sexes and is independent of immunosuppression [ 12 ].
• Anal cancer is much more frequent in HIV-positive homosexual males in com-
parison with HIV-seronegative persons [ 13 ]. All high-risk patients presenting
with anal cancer should undergo HIV testing.
• Presentation of anal cancer in the HIV-positive population does not differ when
compared to the general population. Anal pain, fi ssures, fi stulae, diarrhea, bleed-
ing, and exophytic verrucous anal lesions are the most common clinical manifes-
tations [ 14 ].
• The combination of HAART and chemoradiotherapy is as safe and effective for
immunodefi cient and immunocompetent patients [ 12 – 15 ].
• Pretreatment CD4 count <200/mm 3 increases the likelihood of toxicity, and so
these patients should be treated with caution, while patients with CD4 counts
≥200/mm 3 can be expected to tolerate combined modality therapy.
12.5 Case 3
A 55-year-old woman presented with perianal discomfort and a sensation of irregular skin while cleaning with intermittent “spotting” of bright red blood. She was
previously fi t and healthy apart from a hysterectomy 20 years earlier for cervical
cancer. Local and distant staging confi rmed a T3N1 squamous cell cancer of the
anal canal, and she underwent chemoradiotherapy (45 Gy in 1.8-Gy fractions over
5 weeks) with 5-FU (1000 mg/m 2 per day on days 1–4 and 28–31) and bolus mitomycin (10 mg/m 2 on days 1 and 28, with a maximum of 20 mg per cycle) [ 16 ]. She
had a good clinical response and tolerated therapy well. Examination under anesthesia was performed 12 weeks following completion of chemoradiotherapy. No
abnormality was detected either clinically or histologically. At surveillance EUA 18
months later, she was found to have a lesion at the site of the previous tumor
(Fig. 12.3a ). Biopsy confi rmed it to be a squamous cell carcinoma. Following dis-
cussion at the multidisciplinary meeting (MDM), the decision was taken to perform
a salvage abdominoperineal resection with posterior vaginectomy. A gracilis fl ap
was used. Final histology demonstrated a T3N0M0 tumor (Fig. 12.3b, c ). She made
an uneventful recovery and will have surveillance CT scans to monitor for distant
metastases.
12 Anal C ance r
271
Fig. 12.3 ( a ) Recurrent anal canal cancer . ( b ) Low power of ulcerating residual tumor bed anal
canal. ( c ) H&E section showing focal residual carcinoma where residual tumor cells show a
glandular- type morphology (mucin globules and gland outline)—a well-recognized phenomenon
in post-therapy changes. Near-complete response to neoadjuvant therapy (immunohistochemistry
confi rmed squamous immunophenotype as did review of pretreatment biopsy)
12.5.1 Learning Points
• There is no consensus as to whether physical examination alone is suffi cient fol-
lowing treatment or whether biopsy is necessary in the presence of complete
clinical response.
• Five-year local disease failure rates are different between those patients receiv-
ing radiation alone (52.5 %) and those receiving combined chemoradiation
(35.3 %). In the radiation alone group, age, total radiation dose <50 Gy, and
higher T stage predicted local failure. For patients receiving combined chemora-
diation, no predictive factor was identifi ed [ 17 ].
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A.M. Hogan et al.
• The preferred treatment for persistent disease following combined modality
therapy is APR. The main complications of this procedure are delayed wound
healing, wound infection, and local failure [ 18 ]. Unfortunately wound complica-
tions are common in all previously irradiated skin.
• Salvage chemoradiotherapy has been described, but up to a third of these patients
inevitably ultimately require APR [ 16 ].
• Any patient with a history of cervical cancer should be carefully evaluated for
anal cancer because of the causative role of HPV in both [ 17 ] .
12.6 Case 4
A 39-year-old man presented for day-case hemorrhoidal artery ligation (HAL) for
treatment of hemorrhoids. He was a vague historian but complained of perianal
itch, occasional mucus discharge, and intermittent bright red bleeding per rectum.
He was a smoker with a previous history of genital warts. He was placed in the
lithotomy position, and an examination under anesthesia was performed. The
hemorrhoid at the 7 o’clock position appeared unusual. It was large, bulky, and
polypoid in nature. The operating surgeon decided not to proceed with HAL but to
take multiple biopsies of the unusual hemorrhoid. Histology confi rmed a poorly
differentiated squamous cell carcinoma of the anus (Fig. 12.4a, b ). Local and dis-
tant staging were undertaken, and the patient underwent chemoradiotherapy for
management of anal cancer. He had an excellent clinicopathological response.
Fig. 12.4 ( a ) Invasive nonkeratinizing squamous cell carcinoma . ( b ) Abundant mitoses and cell
pleomorphism indicating poorly differentiated tumor
12 Anal C ance r
273
12.6.1 Learning Points
• A low index of suspicion is essential when dealing with perianal pathology,
and any unexpected fi ndings should be thoroughly investigated to rule out
neoplasia.
• Rectal bleeding should not be ascribed to hemorrhoids unless all other diagnoses
have been defi nitively excluded.
12.7 Case 5
A 47-year-old gentleman presented with anal cancer. He had noticed a “lump” with
associated bleeding some years earlier but due to fear of diagnosis decided not to
present for medical attention. Anal canal biopsy confi rmed an invasive nonkeratinizing SCC . Standardized staging demonstrated multiple bilobar liver metastases
that were deemed unsuitable for surgical resection. Following multidisciplinary
team discussion, the decision was taken to proceed to systemic therapy in the form
of cisplatin and 5-fl uorouracil as well as a targeted dose of 50 Gy radiotherapy. He
tolerated treatment well but, unfortunately, 9 months following diagnosis, staging
radiology demonstrated progression of disease. He underwent second-line chemotherapy but did not demonstrate any clinical response. Following institution of palliative management, he died 3 months later.
12.7.1 Learning Points
• Ten to 20 % of patients will develop distant metastases following combined
modality treatment.
• The prognosis for patients with distant metastases is generally poor, although
documented median survival rates vary from 8 to 34 months [ 19 ].
• The SEER database reports 5-year survival rates of 10 % in men and 20 % in
women with distant metastases from anal cancer at presentation between 1973
and 2000 ( http://seer.cancer.gov/statfacts/html/anus.html ).
• The National Comprehensive Cancer Network (NCCN) Guidelines currently
recommend cisplatin and 5-FU chemotherapy as fi rst-line treatment of meta-
static squamous cell carcinoma ( http://www.nccn.org/professionals/physician_
gls/f_guidelines.asp ).
• Only six randomized trials relating to anal cancer have been performed over the
last three decades (none examining treatment of metastatic disease). Therefore,
available evidence consists of phase II trials, retrospective series, and case reports
only [ 16 , 19 – 24 ].
• The rare nature of metastatic anal cancer does not lend itself well to randomized
control trial design—thus leaving a suboptimal evidence base from which to
d r a w .
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A.M. Hogan et al.
12.8 Case 6
A 68-year-old lady presented with a 6-month history of perianal discomfort and
bright red blood per rectum. She had no family history of colorectal cancer, no
weight loss, and no systemic symptoms. She had had banding of hemorrhoids 10
years previously with a good result and felt that the symptoms she was experiencing were consistent with hemorrhoids. Nonetheless, she underwent full colonoscopy which was normal to the cecum. Digital rectal examination demonstrated
third- degree hemorrhoids at 5, 7, and 11 o’clock positions. Having discussed management options in detail with her, she opted for formal hemorrhoidectomy. All
three hemorrhoids were excised, leaving adequate skin bridges. She had an
uneventful perioperative course and made an excellent recovery. Histology of the
excised specimen was consistent with hemorrhoidal tissue and showed a single
focus of Bowen’s disease within one hemorrhoid. This was completely excised.
Perianal mapping with four quadrant biopsies revealed no further disease. The case
was discussed at a multidisciplinary meeting, and the decision was taken to enroll
the patient on a surveillance program of serial examinations under anesthesia and
biopsies to monitor for recurrence.
12.8.1 Learning Points
• There is a lack of controlled data supporting an optimal treatment strategy for
Bowen’s disease or anal intraepithelial neoplasia serendipitously discovered in
the hemorrhoidal tissue.
• It is considered reasonable by most surgeons to adopt a watch and wait approach
and perform serial examinations under anesthesia to ensure early detection of
recurrence.
• It may present as chronic dermatitis or raised erythematous area with associated
fi ssures.
12.9 Case 7
A 45-year-old woman presented with a 6-month history of intermittent bright red
rectal bleeding. She had not noticed any change in bowel habit, had not lost any
weight, and had no family history of colorectal cancer. She underwent a full colonoscopy which was normal, apart from a deeply pigmented lesion at the anal verge.
This was biopsied and histology confi rmed malignant melanoma (Fig. 12.5a, b ).
Staging CT demonstrated multiple liver, spleen, and bone metastases throughout the
spinal canal. Palliative chemotherapy was commenced and radiotherapy to the spine
for management of bone pain. She died 6 weeks later.
12 Anal C ance r
Fig. 12.5 ( a ) Low power view: ulcerating invasive melanoma . ( b ) Immunohistochemistry—posi-
tivity with mel A and S100
12.9.1 Learning Points
• Anal canal is the third most common site of melanoma after skin and eyes.
• It generally occurs adjacent to the dentate line from melanocytes.
• Bright red bleeding per rectum is the most common presentation.
• Most are highly pigmented lesions but diagnosis remains diffi cult—necessitat-
ing a high level of clinical suspicion.
• Tumors are highly aggressive and usually widely metastatic. For small symp-
tomatic lesion, wide local excision may be considered if negative margins can be
achieved. In the absence of distal disease, whether an abdominoperineal resec-
tion should be considered for locally invasive lesions is still very contentious
with most studies showing no difference in long-term outcomes in patients who
underwent local excision versus APR [ 25 , 26 ].
• Tumors are usually radio- and chemoresistant.
• 5-year survival is <15 %.
275
12.10 Case 8
A 58-year-old lady with severe perineal Crohn’s disease diagnosed 20 years earlier
presented to the outpatient department with a painful, nonhealing fi stula. This had
been treated on several occasions with abscess drainage and with multiple setons to
keep the patient free of sepsis and continent. She had been treated with azathioprine
and infl iximab for the past 17 months. She reported that one particular fi stula was
more painful and associated with increased mucus discharge that was atypical.
Careful EUA revealed a small indurated area below the dentate line, and a punch
biopsy was taken. This had been previously described on magnetic resonance imaging but was not deemed suspicious. Histology demonstrated a squamous cell carcinoma of the anal canal. Because of severe anorectal Crohn’s disease, the option of
276
A.M. Hogan et al.
abdominoperineal resection (APR) was considered but the decision was taken that
the infl amed perineum would be unlikely to heal. A diverting loop colostomy was
performed and she was treated with chemoradiotherapy. Repeat biopsies of the
infl amed area demonstrated infl ammatory tissue only consistent with Crohn’s disease. The anal cancer responded well to local radiotherapy. She was enrolled on a
surveillance program with the aim of early detection of recurrence.
12.10.1 Learning Points
• Squamous cell carcinoma in perianal fi stulae associated with Crohn’s disease is
rare, making diagnosis and management challenging [ 27 – 29 ].
• Anal cell carcinoma may present in an indolent fashion with little or no obvious
external evidence of disease, and so a high index of suspicion is imperative.
• Management of complex perianal disease should be undertaken by personnel
with ample experience in both Crohn’s disease and anorectal cancer and should
involve discussion at a multidisciplinary meeting involving gastroenterologists,
surgeons, radiation oncologists, medical oncologists, pathologists, and
radiologists.
• Because radiotherapy can induce tissue damage, especially in the skin that is
already affected by severe Crohn’s disease, the decision was taken to perform a
diverting loop colostomy for the duration of treatment. In this case, it served dual
purpose—to allow adequate irradiation for treatment of anal squamous cell car-
cinoma and also to facilitate healing of multiple Crohn’s fi stulae.
• If an abdominoperineal resection is indicated, most patients will require a myo-
cutaneous fl ap given the extension of fi stula tracts to anal margins that may be
extensive.
• Clinical management should be patient centered and individualized.
12.11 Case 9
A 62-year-old previously fi t and healthy woman presented to the colorectal service
with a 3-year history of pruritus ani, an erythematous perianal skin rash with
eczema, oozing and scaling, this was associated with constipation. Examination
revealed a circumferential, slightly raised skin lesion extending proximally to the
dentate line. Full physical examination was normal Colonoscopy was normal to
cecum. CT of abdomen and pelvis did not demonstrate any sites suspicious for
metastatic disease. Biopsy of the lesion confi rmed anal Paget’s disease (Fig. 12.6 ).
There was no histological evidence of invasive cancer. She underwent wide local
excision of the lesion surveillance examinations under anesthesia have been negative for 3 years.
12 Anal C ance r
Fig. 12.6 Paget’s cells —
large, pale, clear cells singly
and in clusters
12.11.1 Learning Points
• Anal Paget’s disease is very rare, with less than 200 reported cases in the English
language literature.
• It occurs in the seventh decade of life and affects men and women equally.
• Diagnosis is often delayed because of similarity to other benign anal skin condi-
tions and physician unfamiliarity with the disease.
• For patients who do not have an invasive cancer, a wide local excision is the
treatment of choice. With a noninvasive tumor, survival may approach 100 %.
• Patients initially presenting with invasive disease may be candidates for an
abdominoperineal resection (APR), with an added inguinal lymphadenectomy in
the presence of nodal disease.
• Recurrence rates are reported at 37–100 %. Most can be treated with repeat wide
excision [ 30 ].
• A signifi cant proportion of patients may have an underlying colorectal
neoplasm.
277
12.12 Case 10
A 29-year-old woman presented with skin changes at the anal margin. Ten years
previously she had been treated for cervical carcinoma in situ (CIS). We biopsied
the area which reported anal intraepithelial neoplasia (AIN) with high-grade dysplasia (Fig. 12.7 ). We proceeded to anal mapping in which biopsies were taken in a
circumferential manner from the dentate line downwards. Most of the biopsies
reported AIN with high-grade dysplasia. Given the extensive area of involvement,
we proceeded to a laparoscopic colostomy followed by removal of the involved
perianal skin and anal margin and verge up to the dentate line. Great care was taken
278
Fig. 12.7 Anal
intraepithelial neoplasia III
A.M. Hogan et al.
to protect the underlying sphincter. This area was skin grafted and healed without
fi brosis. The colostomy was closed at 6 months with no change in anorectal
function.
• AIN is a precursor for anal cancer.
• Treatment consists of removal of macroscopic disease with margins.
• Multifocal involvement may necessitate more extensive surgery with potential
for anal canal stenosis and fecal incontinence.
• Even with extensive surgery, there is still an inherent risk of further AIN or anal
canal cancer.
• Other treatment options if the patient is not suitable for surgery include topical
chemotherapy (5-FU), immunotherapy (imiquimod cream 5 % which slows the
progression of disease but 80 % have a relapse after cessation of therapy), pho-
totherapy, and there may be a role for radiotherapy [ 31 ] .
12.13 Case 11
A 50-year-old man was referred by his general practitioner with an anal canal cancer. On examination he also had left inguinal lymphadenopathy. Biopsy of the anal
canal region reported an anal canal adenocarcinoma (Fig. 12.8a ). Biopsy of the
inguinal node reported metastatic adenocarcinoma (Fig. 12.8b ). He underwent
chemoradiotherapy with radiotherapy to include the groin regions. Three months
following neoadjuvant chemoradiotherapy, he then underwent an abdominoperineal
resection with left groin lymphadenectomy.
• Histological confi rmation of an anal canal lesion is critical given the potential for
an atypical malignancy.