Rectal Carcinoma

Description

Rectal carcinoma refers to malignant tumours arising from the lining (epithelium) of the rectum, which is the final portion of the large intestine. The majority of rectal carcinomas are adenocarcinomas, originating from glandular cells in the rectal mucosa.

Pathogenesis

The pathogenesis of rectal carcinoma typically follows the adenoma-carcinoma sequence, in which normal epithelium undergoes a series of transformations from adenomatous polyp to invasive carcinoma. This involves various genetic alterations, including mutations in APC (60% of cases), K-ras (40%), and TP53 genes (50%).

Epidemiology, Risk Factors & Associations

• Rectal carcinoma constitutes about 30% of colorectal cancers.
• It is more common in older adults, typically presenting in the 6th decade of life.
• Risk factors include:
  • Obesity: 30-70% increased risk.
  • Smoking: 20-50% increased risk.
  • Diet high in red or processed meat: 20-50% increased risk.
  • Personal history of inflammatory bowel disease (IBD): 2-3 times higher risk.
  • Alcohol consumption: 10-50% increased risk.
  • Low-fibre diet: 10-20% increased risk.
  • Personal history of adenomatous polyps: 10-20 times higher risk.
  • Hereditary nonpolyposis colorectal cancer (HNPCC): 20% risk.
  • Familial adenomatous polyposis (FAP): Nearly 100% risk if untreated.

Clinical Features

• Patients often present with changes in bowel habits (e.g., diarrhoea, constipation), rectal bleeding, and tenesmus.
• Later stage disease can present with symptoms of obstruction (abdominal pain, bloating) or systemic symptoms such as weight loss and fatigue.

Complications

• Local invasion can lead to obstruction, perforation, and fistula formation.
• Distant metastases, commonly to the liver and lungs, can occur in advanced disease.

Subtypes

Rectal carcinomas are predominantly adenocarcinomas, which can be further classified based on histological features into:

• Conventional (tubular) adenocarcinoma: The most common subtype, composed of gland-forming malignant cells.
• Mucinous adenocarcinoma: Characterised by an abundance of extracellular mucin (>50% of the tumour volume).
• Signet ring cell carcinoma: Contains cells with abundant intracytoplasmic mucin pushing the nucleus to the periphery.

Pathological Features

Morphology

• Rectal carcinomas typically present as an annular, ulcerating, or polypoid mass in the rectum.

Histopathology

• Adenocarcinoma is characterised by invasive glands, lined by columnar cells with nuclear atypia.
• Mucinous and signet ring variants have significant mucin production either extracellularly or within the cell respectively.

Radiological Features

General Features

• Polypoid rectal mass with an irregular surface
• Early cancers: Sessile or pedunculated tumours with short and thick polyp stalk.
• Advanced cancers: Annular, semiannular (C-shaped), polypoid, or carpet tumours
• Most common in rectum: Sessile & polypoid
• Distance from Anal Verge: The distance of the tumour from the anal verge can greatly impact surgical planning and prognosis.
  • Low Rectal Tumours (0-5 cm): These are close to the anal sphincter and may require an abdominoperineal resection (APR) which results in a permanent colostomy.
  • Mid Rectal Tumours (>5-10 cm): May be treated by anterior resection with primary anastomosis, depending on the proximity to the mesorectal fascia (MRF). Tumours threatening or involving the MRF have a higher risk of local recurrence and may necessitate neoadjuvant chemoradiation.
  • High Rectal Tumours (>10-15 cm): These can typically be treated with an anterior resection. The critical aspect is whether the tumour involves the peritoneal reflection, which can influence surgical approach and risk of recurrence.
• Circumferential Resection Margin (CRM): Refers to the shortest distance of the tumour border to the MRF.
  • Tumour ≤ 1 mm of the CRM: Deemed positive, and indicates a high risk of local recurrence and reduced survival.
  • CRM > 1 mm: Associated with a decreased risk of local recurrence and improved survival.
• Extramural Vascular Invasion (EMVI): Extension of the tumour into the veins of the MRF.
  • EMVI is a marker of poor prognosis and metastatic disease, associated with higher T and N stage, positive CRM, and presence of distant metastases.
• Nodal drainage of upper rectal tumors:
  • Regional nodes include the perirectal, presacral, sacral promontory, superior rectal, middle rectal, inferior rectal, sigmoid mesenteric, inferior mesenteric, and internal iliac nodes.
  • Upper rectal tumours typically spread via superior rectal nodes to the inferior mesenteric nodes.

Fluoroscopy

• Early cancer:
  • Sessile (plaque-like) lesion
  • Discrete borders & shallow central ulcers
• Advanced cancer:
  • Polypoid lesion seen as a filling defect in barium pool.
  • Semiannular (saddle- or C-shaped) lesion
  • Annular (apple core) lesion howing circumferential narrowing of bowel
  • “Carpet” lesion: malignant villous tumour appearing with minimal protrusion into lumen.
• High-grade obstruction & ischemia: “Thumbprinting” of dilated proximal colon

CT

• Post-contrast, tumours are typically heterogeneously enhancing.
• Assessment of metastatic disease, including lung & bone metastases before liver metastases
• Evaluation of nodal disease and peritoneal carcinomatosis
• Identification of extracolonic tumor extension and loss of tissue fat planes

MRI

• MRI, particularly with a rectal protocol, is the imaging modality of choice for local staging, assessing the depth of invasion (T stage), and involvement of mesorectal fascia.
• T2-weighted images can help differentiate the layers of the rectal wall and thus determine the T stage.

PET

• PET-CT can be useful for identifying distant metastases, particularly in cases where curative surgery is considered.

Grading and Staging

T Stage (Primary Tumour):

• T0: No evidence of primary tumour.
• Tis: Carcinoma in situ (tumour cells only within the epithelium).
• T1: Tumour invades submucosa.
• T2: Tumour invades muscularis propria (muscle layer of the rectal wall).
• T3: Tumour invades through the muscularis propria into perirectal fat.
  • T3a: Tumour invasion is less than 1 mm into perirectal fat.
  • T3b: Tumour invasion is 1-5 mm into perirectal fat.
  • T3c: Tumour invasion is more than 5 but less than 15 mm into perirectal fat.
  • T3d: Tumour invasion is more than 15 mm into perirectal fat.
• T4: Tumour invades nearby structures or organs.
  • T4a: Tumour penetrates the surface of the visceral peritoneum.
  • T4b: Tumour directly invades or is adherent to other organs or structures.

N Stage (Lymph Nodes):

• N0: No regional lymph node involvement.
• N1: Metastasis to 1 to 3 nearby lymph nodes.
  • N1a: Metastasis in 1 regional lymph node.
  • N1b: Metastasis in 2 to 3 regional lymph nodes.
  • N1c: Tumour deposit(s) in the subserosa, mesentery, or non-peritonealised pericolic or perirectal tissues without regional nodal metastasis.
• N2: Metastasis in 4 or more nearby lymph nodes.
  • N2a: Metastasis in 4 to 6 regional lymph nodes.
  • N2b: Metastasis in 7 or more regional lymph nodes.

M Stage (Distant Metastasis):

• M0: No distant metastasis.
• M1: Distant metastasis present.
  • M1a: Metastasis to 1 organ or site without peritoneal metastasis.
  • M1b: Metastasis to 2 or more sites or the peritoneum without other organ metastasis.
  • M1c: Metastasis to the peritoneum with or without other organ metastases.

The staging of rectal cancer involves the combination of the T (tumour), N (nodes), and M (metastasis) categories.

Stage I (Early stage):

• Stage IA: T1, N0, M0: The cancer has grown through the innermost layer of the colon or rectum but hasn’t spread beyond the muscularis propria (T1). No cancer is found in nearby lymph nodes (N0) or distant sites (M0).
• Stage IB: T2, N0, M0: The cancer has spread to the muscularis propria (T2) but not to nearby lymph nodes (N0) or distant sites (M0).

Stage II (Locally advanced):

• Stage IIA: T3, N0, M0: The cancer has spread through the muscularis propria to the subserosa or into the fibrous tissues surrounding the colon or rectum (T3). It hasn’t spread to the nearby lymph nodes (N0) or distant sites (M0).
• Stage IIB: T4a, N0, M0: The cancer has penetrated the surface of the visceral peritoneum (T4a). It hasn’t spread to the nearby lymph nodes (N0) or distant sites (M0).
• Stage IIC: T4b, N0, M0: The cancer has invaded or adhered to other organs or structures (T4b). It hasn’t spread to the nearby lymph nodes (N0) or distant sites (M0).

Stage III (Regional spread): The cancer has spread to nearby lymph nodes but not to other parts of the body. It includes:

• Stage IIIA:
  • T1 or T2, N1/N1c, M0
  • T1, N2a, M0
• Stage IIIB:
  • T3 or T4a, N1/N1c, M0
  • T2 or T3, N2a, M0
  • T1 or T2, N2b, M0
• Stage IIIC:
  • T4a, N2a, M0
  • T3 or T4a, N2b, M0
  • T4b, N1/N2, M0

Stage IV (Metastatic disease): The cancer has spread to distant lymph nodes or organs:

• Stage IVA: Any T, any N, M1a: The cancer has spread to one distant organ (such as the liver or lung) or distant set of lymph nodes, but not the peritoneum (the lining of the abdominal cavity).
• Stage IVB: Any T, any N, M1b: The cancer has spread to more than one distant organ (such as the liver or lung), the peritoneum, or it has spread to one organ and also to distant lymph nodes.

Differential Diagnosis

• Diverticular Disease: Characterised by sac-like protrusions in the colonic wall, often asymptomatic but may present with abdominal pain, bloating and alteration in bowel habits. Diverticula, especially when inflamed, can cause thickening of the colonic wall mimicking a mass on imaging. However, the presence of multiple diverticula and lack of mass-like lesion aids in differentiating from carcinoma.
• Inflammatory Bowel Disease (Ulcerative Colitis and Crohn’s Disease): Chronic inflammatory conditions with characteristic symptoms of abdominal pain, diarrhoea, and rectal bleeding. Continuous pattern of inflammation in ulcerative colitis and skip lesions in Crohn’s disease, along with the absence of a discrete mass, can help distinguish these conditions from rectal carcinoma.
• Colonic Polyps (Adenomatous, Hyperplastic): Asymptomatic in most cases, detected during routine colonoscopy. Polyps are generally smaller and more uniform than carcinoma. However, adenomatous polyps are precursors to colorectal cancer, and large or villous adenomas can be difficult to distinguish from early cancers.
• Anal Fissures and Haemorrhoids: Characterised by rectal bleeding, pain during bowel movements, and itching These conditions do not produce a mass lesion, and their symptoms, while overlapping with rectal cancer, can often be distinguished by physical examination.
• Colorectal Tuberculosis: Can present with non-specific symptoms like abdominal pain, weight loss, and sometimes rectal bleeding. History of tuberculosis, evidence of systemic tuberculosis infection, and response to anti-tuberculous therapy is key. On imaging, the presence of lymphadenopathy with central necrosis is a clue to tuberculosis.
• Solitary Rectal Ulcer Syndrome: Chronic disorder that presents with rectal bleeding, straining, and constipation. Endoscopy reveals a solitary ulcer in the rectum, usually anteriorly, without a mass lesion.
• Rectal Lymphoma: Typically presents with non-specific gastrointestinal symptoms. Lymphoma of the rectum is rare, and it usually causes diffuse wall thickening rather than a focal mass. Biopsy shows lymphoid cells rather than the glandular cells seen in adenocarcinoma.
• Rectal Neuroendocrine Tumours (Carcinoids): Often asymptomatic, but can secrete hormones leading to symptoms like diarrhoea, flushing, and wheezing. These are rare and typically smaller than adenocarcinomas. Histologically, these tumours are made up of neuroendocrine cells and can be confirmed by immunohistochemical staining.
• Anal Carcinoma: Symptoms can include rectal bleeding, anal pain, change in bowel habits and pruritus. In advanced cases, there may be the presence of an anal mass. Anal carcinoma often presents with symptoms similar to benign anal disorders such as haemorrhoids or anal fissures, which can delay diagnosis. It is distinguished by its location (anal canal and perianal skin), associated risk factors (e.g., human papillomavirus infection, immunosuppression), and its histological subtype (typically squamous cell carcinoma). Additionally, anal carcinoma can be associated with ulceration, which is less commonly seen in rectal adenocarcinoma.

Management

• Management is multidisciplinary and involves gastroenterology, surgical oncology, medical oncology, and radiation oncology teams.
• Depending on the stage of the disease, treatment options include surgery, chemotherapy, radiotherapy, or a combination of these.
• Biopsies are typically obtained during colonoscopy for confirmation of diagnosis and initial staging.