Chapter 27 – Non-Neoplastic Diseases of the Anal Canal


The commonest non-neoplastic conditions in the anal canal include haemorrhoids, fissures, fibroepithelial polyps and associated abscesses, manifestations of Crohn’s disease, Human Papilloma Virus infection, and other sexually transmitted infections (some of which are secondary to HIV). Several dermatoses that are not site-specific may also involve the anal canal and perianal areas. These include eczema, psoriasis, lichen planus, lichen sclerosus, acanthosis nigricans, and hidradenitis suppurativa. Non-neoplastic polypoid lesions may occur, and these include condylomata acuminata and inflammatory cloacogenic polyps. Congenital abnormalities include imperforate anus and anal duplication. The former rarely, if ever, comes to attention of the histopathologist whereas the latter is occasionally encountered.

Chapter 27 Non-Neoplastic Diseases of the Anal Canal

Morgan Moorghen


The anal canal measures approximately 4 cm in length and extends from the caudal end of the rectum to the anal verge. In its proximal part it has a lining of columnar mucosa and distally a lining of stratified squamous epithelium. The dentate line is the point of demarcation in the anal canal between the embryological endoderm and the ectoderm. Just above the dentate line lies the transitional zone, which is of variable length, generally between 1 and 2 cm. The anal canal is entirely extra-peritoneal. The wall of the anal canal is composed of striated muscle and smooth muscle. The internal anal sphincter is composed of smooth muscle and is a continuation of the inner muscular layer of the rectal muscularis propria whereas the external anal sphincter is composed of striated muscle.1

The most common non-neoplastic conditions in the anal canal include haemorrhoids, fissures, fibroepithelial polyps and associated abscesses, manifestations of Crohn’s disease, human papilloma virus infection, and other sexually transmitted infections (some of which are secondary to Human immunodeficiency virus [HIV]). Several dermatoses that are not site-specific may also involve the anal canal and perianal areas. These include eczema, psoriasis, lichen planus, lichen sclerosus, acanthosis nigricans, and hidradenitis suppurativa. Non-neoplastic polypoid lesions may occur and include condylomata acuminata and inflammatory cloacogenic polyps. Congenital abnormalities include imperforate anus and anal duplication. The former rarely, if ever, comes to attention of the histopathologist whereas the latter is occasionally encountered.


In the normal anal canal there are protrusions of the submucosa forming vascular cushions or haemorrhoidal cushions, typically located in the right anterior, right posterior, and left lateral aspects. Histologically these are composed of blood vessels, smooth muscle, and collagenous connective tissue and are identifiable as normal anatomical structures.2 They allow the maintenance of normal faecal continence, but abnormal protrusion of these hemorrhoidal cushions may lead to symptoms. The clinical presentations of haemorrhoidal disease relate to pruritus, prolapse, thrombosis, and bleeding. The factors that lead to the development of haemorrhoidal disease include constipation, prolonged straining, nutritional factors (in particular low-fibre diet), pregnancy, and high intra-abdominal pressure. There are no obvious genetic factors. The varices seen in portal hypertension share features with haemorrhoids but are not true haemorrhoids.

Clinically, there are two types of haemorrhoid: internal haemorrhoids, which are located proximal to the dentate line, and external haemorrhoids, which arise below the dentate line. Internal haemorrhoids tend to give rise to painless bright red bleeding, but other presentations include itching, a burning sensation, and mucus discharge. External haemorrhoids tend to cause itching and perianal moisture but rarely cause pain unless complicated by thrombosis, in which case a firm nodule may be visible and palpable on clinical examination. The usual treatment is conservative and non-surgical. Surgery is reserved for the more severe cases.

For the histopathologist, there are essentially two types of specimen. One is the haemorrhoidectomy specimen, which comprises an excised vascular cushion, and the other is the stapled haemorrhoidectomy specimen. The histopathologist should confirm the presence of vascular structures and supporting connective tissue (Figure 27.1), comment on the presence, if any, of recent or old re-canalised thrombus and, in the case of the stapled haemorrhoidectomy specimen, confirm the presence of mucosal prolapse changes (which are almost universally present). Surgeons also may wish to know if muscularis propria is included, particularly for stapled haemorrhoidectomies.

Figure 27.1 Haemorrhoid. Dilated vascular channels are present. Smooth muscle fibres are apparent in the stroma.

In a few cases, histological examination reveals incidental findings with serious implications for the patient. These include malignancies such as malignant melanomas and carcinomas. Other less serious but clinically significant incidental findings may occur, particularly anal intraepithelial neoplasia (AIN). In one study of 2663 haemorrhoidectomies from a unit with a relatively high prevalence of HIV-positive patients, there was high-grade AIN in 1.8% (48 cases) and squamous cell carcinoma in 0.26% (7 cases),3 while other studies reported lower rates. Such incidental changes help to justify the common practice of submitting all haemorrhoidectomy specimens for histopathological examination.4 However, some authors argue for a selective approach whereby histological examination is restricted to the specimens that show suspicious macroscopic features such as a nodule or mass (Practice Points 27.1).5

Practice Points 27.1 Haemorrhoids

Types of Specimen

  • Haemorrhoidectomy

  • Stapled haemorrhoidectomy

Features to Include in the Report

  • Vascular structures

  • Thrombosis

  • Connective tissue

  • Mucosal prolapse changes

  • Presence or absence of muscularis propria

Possible Incidental Changes

  • AIN

  • High-grade AIN (<2%)

  • Squamous cell carcinoma (<0.5%)

  • Melanoma (very rare)

Anal Fissure

An anal fissure is a linear and usually painful ulcer in the posterior part of the anal canal below the dentate line. Typically, it presents in young and middle-aged individuals. The most common cause is trauma from hard bowel movements. The diagnosis is usually based on history and clinical examination. Most anal fissures either heal spontaneously or resolve following conservative measures. In some cases, a chronic fissure appears with the development of fibrotic edges and, eventually, the formation of a sentinel pile. When the cause is not obvious clinically, e.g. when a hard nodule has developed at the edges or when the fissure is in an unusual location, the lesion may be biopsied. In these circumstances, the differential diagnoses include Crohn’s disease, neoplasia, and an infective process. As regards infections, specific HIV-related complications are a consideration if there is any clinical suspicion of this diagnosis.

Anal Fissures in Crohn’s Disease

Anal fissures, particularly chronic anal fissures, are more common in inflammatory bowel disease (IBD) than in the population.6, 7 In most cases, a clinical diagnosis of IBD, particularly Crohn’s disease, predates the clinical presentation of a fissure. In the absence of a positive clinical history, a histological diagnosis of Crohn’s in a fissure relies heavily on the presence of granulomatous inflammation. However, foreign body-type granulomas are not uncommon in anal fissures regardless of the aetiology of the fissure. Therefore, a histological diagnosis of Crohn’s disease based on the examination of anal fissure samples merits a cautious approach, even if granulomas are present (Fact Sheet 27.1 and Practice Points 27.2).

Fact Sheet 27.1 Anal Fissures

Reasons for Biopsy

  • Unusual location

  • Nodularity

  • Firm consistency

  • Clinical suspicion of neoplasia

Possible Causes

  • Crohn’s disease

  • Neoplasia

  • Infection

  • HIV-related diseases

Practice Points 27.2 Fissures in Crohn’s Disease

  • In IBD-related fissures, a clinical diagnosis of IBD often precedes the development of the fissure.

  • In the absence of a history of IBD, granulomas raise the possibility of Crohn’s disease but also have other causes, e.g., reaction to foreign material.

  • A diagnosis of Crohn’s disease should be cautious in the setting of a fissure.

Anal Fissures and HIV

Patients with HIV infection often present with anal ulcers and fissures. These have a variety of appearances and locations in the anal canal but are often indistinguishable from anal fissures in the general population.

Anal Tags

Anal tags are folds of squamous mucosa that represent a reparative hyperplastic response to recent injury. Therefore, they may develop in relation to anal fissures, haemorrhoids, mechanical damage, fistulae, and Crohn’s disease. Clinically, there are two types: the soft broad-based painless tags referred to as ‘elephant ears’ and the hard oedematous and tender nodule.8 The latter typically arises in relation to a fissure, haemorrhoid, or ulcer, whereas the former has an association with Crohn’s disease. In both types of anal tag, the histological features are those of squamous acanthosis with variable hyperkeratosis and papillomatosis. In the stroma there is fibrosis with stellate fibroblasts. Multinucleate cells may also be present (Figure 27.2). Granulomas, if present, are highly suggestive of Crohn’s disease, and in many cases precede the development of intestinal inflammation (Fact Sheet 27.2).

Figure 27.2 Anal tag. This has a covering of stratified squamous epithelium. In the stroma there are stellate cells.

Fact Sheet 27.2 Fibroepithelial Polyps / Skin Tags


  • Anal fissures

  • Haemorrhoids

  • Mechanical damage

  • Fistulas

  • Crohn’s disease

Two Types

  • Soft broad-based painless tags (‘elephant ears’): associated with Crohn’s disease

  • Hard oedematous tender nodules: often related to fissure, haemorrhoid, or ulcer

Histological Features

  • Squamous acanthosis with papillomatosis and hyperkeratosis

  • Stromal fibrosis with stellate fibroblasts

  • Possible presence of multinucleate cells


  • Granulomas in skin tags strongly suggest Crohn’s disease

  • Granulomas occur in 25% of Crohn’s-related anal skin tags

  • Crohn’s-related skin tags may precede intestinal inflammation

Anal Abscess and Anal Fistula

Anal or anorectal abscesses consist of collections of pus in one of four potential anorectal spaces, i.e. the perianal space which is located deep to the junction between the anal canal and perianal skin, the ischiorectal space, the space above the levator muscle, or the intersphincteric space. Most of these abscesses are probably of cryptoglandular origin in that they develop following infection of obstructed dilated anal glands and ducts.9 Crohn’s disease represents the next most common cause. Other causes of abscesses include previous surgery, trauma, actinomycosis, mycobacterial infections, lymphogranuloma venereum, radiation, malignancy, and immunosuppression (Fact Sheet 27.3). Fistula formation may complicate these abscesses if they fail to heal.

Fact Sheet 27.3 Anal Abscesses

Causes of Anal Abscesses

  • Infection of obstructed dilated anal glands and ducts (cryptoglandular abscess)

  • Crohn’s disease

  • Previous surgery

  • Trauma

  • Actinomycosis

  • Mycobacterial infection

  • Lymphogranuloma venereum

  • Radiation

  • Malignancy

  • Immunosuppression

The surgical management of anal fistulae often includes submission of tissue for histological examination. During histological assessment, the presence of anal glands/ducts associated with inflammation is worth recording, as it lends support to a cryptoglandular origin of the abscess. In relation to Crohn’s disease, any positive clinical history becomes a useful pointer when taken together with the presence of Crohn’s-type granulomas. There are other causes of granulomas in this setting, particularly foreign material. As is the case for fissures, a diagnosis of Crohn’s disease on the basis of the appearances of fistula material should be cautious, even if granulomas are present.

Persisting disease may require fistulectomy. Typically, the fistula lining is partly epithelial (columnar, squamous or transitional-zone epithelium) and partly granulation tissue, and there is surrounding fibrosis. The extent of epithelialisation may be associated with time of duration of a persistent fistula.9 In most cases, a routine search for bacteria with a Gram stain is not necessary since their identification has little or no bearing on further management. However, there are rare cases of fistulae complicated by actinomyces and/or mycobacteria.10, 11 For actinomyces, the presence of colonies forming typical sulphur granules in haematoxylin and eosin (H&E) sections would point to the correct diagnosis (Figure 27.3). Mycobacterial superinfection sometimes results in caseation, which may be apparent macroscopically (Figure 27.4), and granulomas (Fact Sheet 27.4).

Figure 27.3 Actinomyces colonies forming typical sulphur granules. (Courtesy of Dr Laura Lamps, University of Michigan, USA.)

Figure 27.4 Tuberculosis in a fistula tract. Note the presence of granulation tissue with a suggestion of caseation.

Fact Sheet 27.4 Anal Fistulas

Common Causes

  • Infection

  • Crohn’s disease

  • Neoplasia


  • Lined by epithelium (columnar, squamous or transitional) and granulation tissue

  • Surrounded by fibrosis

  • Searches and/or stains for bacteria are unnecessary

  • Rarely complicated by actinomyces and/or mycobacteria

Anal Crohn’s Disease

In Crohn’s disease, involvement of the anal canal takes various forms. These include fistulae, skin tags, fissures, strictures, and abscesses.6 In Crohn’s disease, anal fissures often occur in locations other than the midline and are typically painless. They heal either spontaneously or after treatment with topical or systemic therapy. A tissue diagnosis is often unnecessary and indeed may be discouraged because of the risk of complications related to poor healing after biopsy. Anal ulceration is a frequent feature of Crohn’s disease, is usually cavitating, and is often associated with a proctitis. Longstanding ulceration may be complicated by a stricture, in turn requiring biopsy and a tissue diagnosis in order to exclude neoplasia. Anal and perianal skin tags are frequent in Crohn’s disease and often predate intestinal inflammation. Diagnostic granulomas occur in up to 25% of skin tags from those with Crohn’s disease.12

Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of unknown aetiology that affects various apocrine gland-bearing areas. It occurs after puberty with a 3:1 female/male ratio. However, perianal HS is more frequent in male than in female patients. The disease starts as a deep folliculitis complicated by abscess formation, followed by the development of sinuses and fibrous scarring. Earlier descriptions of HS identified involvement of apocrine glands as an initiating event, but in practice an ‘apocrinitis’ is rare and a folliculitis much more common. There are many similarities between Crohn’s disease and hidradenitis suppurativa. Both fall within the spectrum of chronic auto-inflammatory diseases and are characterised by dysregulation of the innate and adaptive immune responses.13 Furthermore, there is a higher prevalence of hidradenitis suppurativa in patients with IBD. Distinction between HS and Crohn’s disease in biopsy material can be difficult (Table 27.1). The difficulty is worsened by the fact that both diseases may occur concurrently. Therefore, clinicopathological correlation is essential. A related consideration is that Crohn’s disease is associated with a number of cutaneous extra-intestinal manifestations, including erythema nodosum, pyoderma gangrenosum, and erythema multiforme. Granulomas can help distinguish Crohn’s disease from HS, although foreign body-type granulomas associated with follicular rupture may be present in HS (Figure 27.5A and B).

Table 27.1 Comparison of cutaneous Crohn’s disease and hidradenitis suppurativa

Crohn’s disease Hidradenitis suppurativa
Granulomas: typically Crohn’s type Granulomas: foreign body type
Fistula is a well-recognised feature There is a higher incidence of HS in fistulating Crohn’s
Follicular plugs and folliculitis are not a specific feature of Crohn’s disease.

  • Follicular plugs and folliculitis typical of HS

  • Evidence of follicular destruction with cytokeratin stain may help in diagnosis

Macroscopic scarring, usually associated with fistulae Macroscopic scarring, often without fistulae
Ileocolonic Crohn’s supports diagnosis Ileocolonic Crohn’s: suggests coexisting Crohn’s

HS, hidradenitis suppurativa.

(A) Inflammation in the subcutis with granulation tissue from edge of fistula at deep aspect.

(B) Inflammation around sweat glands.

Figure 27.5 Hidradenitis suppurativa (in perianal skin).


Diseases of the anorectum are common in HIV patients and are often the primary reason for consultation. The presenting lesions include incidental common pathology, e.g. haemorrhoids, fissures, ulcers, and abscesses. Diagnosis and treatment of haemorrhoids is much the same as in non-HIV patients. When anal fissures occur, HIV-associated ulcers require careful exclusion. They typically occur above the dentate line, whereas fissures in the general population are located more distally. The aetiology of HIV-associated lesions includes herpes simplex virus (HSV), cytomegalovirus (CMV), syphilis, Mycobacteria, Cryptococcus, Haemophilus ducreyi, and Chlamydia (Fact Sheet 27.5).

Sep 2, 2020 | Posted by in GASTROENTEROLOGY | Comments Off on Chapter 27 – Non-Neoplastic Diseases of the Anal Canal

Full access? Get Clinical Tree

Get Clinical Tree app for offline access