GS20 - Incidental Discovery of Advanced Primary Anal Adenocarcinoma

Introduction/Purpose:
Primary carcinoma of the anus is relatively rare, accounting for only 2.7% of all gastrointestinal malignancies with an age-adjusted incidence of 1-2 per 100,000 per year [1,2]. Approximately 85% of primary anal carcinomas are squamous cell in origin with a well-described risk profile, presentation, and clinical course [3]. Persistent infection with high-risk strains of human papillomavirus (HPV) is a well-documented risk for the development of anal squamous cell carcinoma and anal intraeithelial neoplasia, however there is no association with HPV infection and anal adenocarcinoma [4]. Other causes of primary anal cancer are much less common, including adenocarcinoma, basal cell carcinoma, Paget disease, Bowen disease, and melanoma [5].



Presenting symptoms of anal cancers are often non-specific and can be related to blood loss, pain on defecation, proctitis or visualization [6]. However, symptoms may oftentimes be attributed to other benign causes such as hemorrhoids, fissures, or physical irritation. When anal cancers are suspected, an excisional biopsy can confirm the diagnosis. It is hypothesized that adenocarcinoma originates from the columnar epithelium of the anal glands around the transition zone of the anal canal [7].



Staging often involves CT scan of the abdomen and pelvis in addition to colonoscopy and PET scan to detect lymph node involvement [6]. The dentate line serves as an anatomical landmark for the lymphatic drainage of the anal canal. Lesions distal to the dentate line drain into the inguinal and femoral lymphatics, while lesions proximal to the dentate line will drain into the superior rectal lymphatics and into the inferior mesenteric nodes [8]. Therefore careful physical exam in conjunction with appropriate diagnostic imaging is crucial during the initial evaluation.



The traditional management for anal squamous cell carcinoma is chemoradiation with abdominoperineal resection in severe cases. Due to the rare nature and worse prognosis of anal adenocarcinoma, patients have traditionally been treated similar to primary rectal adenocarcinomas with neoadjuvant chemoradiation followed by abdominoperineal resection [9].



Adenocarcinoma of the anal canal accounts for only 10% of all anal carcinoma diagnoses; however, the literature regarding the natural history and clinical course remains sparse. We present a case of an advanced presentation of anal adenocarcinoma in a 65 year old female.

Methods or Case Description:
A 65 year-old female was admitted to the medical service for COPD exacerbation and iron deficiency anemia. On day 2 of admission, the general surgery service was consulted for evaluation of a large anal mass lesion discovered by the RN caring for the patient.



On physical exam, the patient was found to have a large friable, ulcerated, and partially necrotic mass involving the anal canal, anoderm, and surrounding skin at the 8 o’clock position. Further examination revealed a hard and fixed left inguinal lymph node. Upon further history, the lesion had been present for 2-3 months prior to admission and the patient had been experiencing bleeding and discomfort with bowel movements. Based on history and initial evaluation, the lesion was presumed to be of squamous cell origin and was highly suspicious for metastatic disease.



The patient underwent a needle biopsy of the left inguinal node and anal exam under anesthesia 2 days later which revealed an extensive, friable, ulcerated mass measuring roughly 5 x 5cm and extending into the anal canal. Excisional biopsy of the mass revealed invasive adenocarcinoma with focal mucinous features and strong reactivity for cytokeratin 7 (Figure 1, 2). The mass was also focally reactive for p16.





Figure 1.





Figure 2.



Lymph node biopsy revealed fibrotic and partially necrotic soft tissue with adenocarcinoma (Figure 3).





Figure 3.



IHC staining demonstrated strong reactivity for cytokeratin 7 with focal reactivity for p16 confirming the source (Figure 4).





Figure 4.



As the mass was confirmed to be adenocarcinoma it was highly suspicious to be of gynecologic origin. The patient underwent a CT of the abdomen and pelvis which revealed left groin adenopathy but was otherwise negative (figure 5.)





Figure 5.



A decision was made to create a diverting colostomy to allow the area to heal and prevent more blood loss. The patient was taken to the OR and a diverting colostomy was created in the left lower quadrant. She was subsequently discharged for outpatient oncology follow-up and metastatic workup.

Outcomes:
Primary adenocarcinoma of the anus is a rare entity that often presents in women and older patients. Recent data has shown the possibility that immunosuppression, inflammatory bowel disease, and older age may be risk factors for the development of anal adenocarcinoma due to the increased reepithelialization of the anal canal [3].



In this patient, the anal mass biopsied expressed cytokeratin 7, a structural protein found in ductal and glandular epithelium [10]. This was consistent with a diagnosis of adenocarcinoma. The anal mass was also expressed patchy reactivity for CDX2 and cytokeratin 20. CDX2 is an intestine-specific transcription factor that is seen in colorectal and other gastrointestinal adenocarcinomas, as well as some ovarian mucinous tumors [11]. Cytokeratin 20 is a structural protein confined to gastric, intestinal, urothelium, and Meckel cells [12].



The inguinal lymph node biopsy also revealed cytokeratin 7 positivity. The node was also focally positive for p16, a tumor suppressor gene involved in the regulation of the p53 and RAS pathways. Upregulation of p16 is commonly found in HPV infection, however, this patient was HPV negative [13].



The immunohistochemistry analysis of the anal mass and inguinal lymph node biopsy assists in ruling out a gynecologic origin of this patient’s adenocarcinoma. However, additional radiographic and clinical exploration is necessary to definitively rule out gynecological origin.



Due to the rare nature of the disease, the clinical course of anal adenocarcinoma is poorly described in the literature. A worse prognosis and 5-year survival has been documented for anal adenocarcinoma versus lower rectal adenocarcinoma and squamous cell carcinoma [5,14]. Traditionally, anal adenocarcinoma was treated similarly to rectal adenocarcinoma with abdominoperineal resection, however, new literature suggests that neoadjuvant therapy confers the greatest survival benefit [4,7]. Neoadjuvant therapy may include radiation and chemotherapeutic agents such as 5-fluorouracil and oxaliplatin, which aim to decrease cell division prior to surgical resection. The decision to proceed with neoadjuvant therapy should be based on tumor staging through MRI to assess for local invasion of the disease and CT scans to assess distal spread [15].

Conclusion:
Adenocarcinoma of the anus presents a clinically challenging multidisciplinary problem for surgeons, gastroenterologists, and oncologists. The lack of literature on the topic underlies the rareness. As more cases are described perhaps there will be a more robust set of clinical guidelines and treatments protocols.