Synchronous anal canal carcinoma in a heterosexual couple

A 60-year-old woman sought medical attention after a 2-month history of minor rectal bleeding and an anal nodule. On physical examination, a 3-cm mobile anterior ulcerative mass in the anal canal was palpable, beginning at 1 cm from the anal verge with no extension to the anorectal junction. No nodes were appreciated in the inguinal regions. A biopsy revealed an invasive squamous cell carcinoma, well-differentiated (Fig. 1a). Staging computerized tomography (CT) of the thorax/abdomen/pelvis did not show any lymphadenopathy or distant metastatic disease. Pelvic magnetic resonance imaging (MRI) demonstrated a 3-cm mass in the anal canal extending to the anorectal junction (Fig. 2a and b). There was no pelvic or inguinal lymphadenopathy. Her laboratory investigations including HIV-1 and HIV-2 serology were negative. A recent Papanicolau smear of the cervix was reported to be negative for intraepithelial lesion or malignancy.

The patient had a past medical history remarkable for an in-situ cervical carcinoma treated with laser therapy over 20 years ago with no subsequent recurrence. She also underwent a right salpingo-oophorectomy for an endometriotic cyst of the right ovary 8 years prior to her anal canal cancer diagnosis. She is a life-time non-smoker and social alcohol drinker. There was no past history of any autoimmune disorders.

For her T2N0M0 anal cancer, the patient underwent a course of chemo-radiotherapy as per institutional protocol. The total dose was 54 Gy in 30 daily fractions to the primary and elective nodal irradiation consisted of 36 Gy in 20 fractions to the inguinal/femoral, mesorectal, presacral and external/internal iliac nodal regions. The radiation treatment was delivered using volumetric modulated arch therapy (VMAT) technique. The chemotherapy regimen consisted of mitomycin C (10 mg/m² on day 1) and infusional 5-fluorouracil (1000 mg/m²/day for 4 days), given concurrently on week 1 and week 5 of radiation. The patient developed RTOG grade 3 skin and perineal reactions. She had an episode of fever without neutropenia managed by oral antibiotics.

While the female was undergoing chemoradiation, her husband, with whom she has been married for over 30 years, requested a screening colonoscopy during his regular urological follow-up. The investigation revealed an anal mass that was biopsied and demonstrated a poorly-differentiated squamous cell carcinoma with prominent lymphoid infiltration (Fig. 1b). This 63 year-old man was largely asymptomatic. After diagnosis, he was referred to the same cancer centre where his wife received oncological care. On physical examination, an ulcerative exophytic mass was seen, measuring approximately 3 cm in maximum dimension, located over the posterior third of the anal canal at 2 cm from the verge. The mass extended to the anorectal junction. No inguinal nodes were clinically suspicious. Staging CT and MRI revealed at least four suspicious mesorectal nodes and a 1.8-cm left external iliac lymph node. There was no evidence of distant metastatic disease. On MRI, the maximum tumor dimension of the primary was 3 cm (Fig. 2c and d). Similar to his wife, this man’s HIV serology was negative. He was a non-smoker. There was no previous history of sexually transmissible disease, and he denied any receptive anal intercourse or sex with men. He was on tamsulosin 0.4 mg and dutasteride 0.5 mg for benign prostatic hyperplasia.

This patient was treated with the same institutional protocol of chemoradiation for his T2 N2 anal cancer with a total dose of 54 Gy to the primary and the involved nodes plus concurrent chemotherapy with 5-fluorouracil and mitomycin C. The elective nodal irradiation dose was 36 Gy. The patient developed neutropenia and thrombocytopenia, diarrhea, oral mucositis and the usual perianal/perineal skin reaction.

The immunohistochemical profiles of both the wife’s and husband’s lesions were similar. Both tumours demonstrated diffuse and strong immunoreactivity for p16 (Fig. 1c-d) suggesting high-risk HPV infection [8] and neither exhibited p53 overexpression or p53 loss. PCR for HPV genotype was performed using the Cobas 4800 HPV Test System [9]. HPV16 DNA was detected in both lesions. The two lesions were negative for HPV18 and also negative for HPV31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68.