Primary anal mucinous adenocarcinoma: A case series

Arab Journal of Gastroenterology 12 (2011) 48–50

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Case Report

Primary anal mucinous adenocarcinoma: A case series Azeddine Diffaa a,⇑, Zouhour Samlani a, Abouch Elbahlouli a, Khalid Rabbani b, Youssef Narjis b, Fadoua Elamansouri c, Salwa Ettalbi d, Elhassan Boukind e, Badia Belabidia c, Hamid El Idrissi b, Khadija Krati a a

Gastroenterology Department, UHC Mohamed VI Qaddi Ayyad University, Marrakech, Morocco General Surgery Department, UHC Mohamed VI Qaddi Ayyad University, Marrakech, Morocco Pathology Department, UHC Mohamed VI Qaddi Ayyad University, Marrakech, Morocco d Plastic Surgery Department, UHC Mohamed VI Qaddi Ayyad University, Marrakech, Morocco e Plastic Surgery Department, UHC Ibn Rochd, Casablanca, Morocco b c

a r t i c l e

i n f o

Article history: Received 7 May 2010 Accepted 9 December 2010

Keywords: Mucinous adenocarcinoma Mucous Anus Malignant tumour

a b s t r a c t Primary mucinous adenocarcinoma is a rare malignancy of the anus (3% of anal cancers), the pathogenesis of which is better understood by immunohistochemistry. We reviewed cases of primary mucinous adenocarcinoma of the anus from 2000 to 2009 in the Hepatogastroenterology Department of the University Hospital Centre of Marrakech. Three cases were identified who were males with the mean age of 68 years, and presented with a chronic anal fistula. Two cases had anal pain. Clinical examination revealed multiple fistulae in two cases with a secretion simulating ‘cooked grains of tapioca’. Diagnosis was confirmed by histopathology and immunohistochemical profile (CK7 positive/CK20 negative). Imaging revealed a retro-rectal collection with thickening of the anal wall without metastasis (two cases). One patient underwent abdominoperinal resection without recurrence. Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved.

Introduction Primary mucinous adenocarcinoma is a rare malignant tumour of the anus (3% of anal cancers). Currently, its pathogenesis is better understood by immunohistochemical studies of keratins and mucins. In this report we describe the features in three cases diagnosed at our center. Case Out of the 28 anal adenocarcinomas presented to the Hepatogastroenterology Department of Mohamed VI University Hospital Center of Marrakech (Morocco) in the period from January 2000 to December 2009 three cases with primary mucinous adenocarcinoma were identified. Table 1 summarizes the data of these cases. All cases were males with a mean age of 68 years. All three cases had chronic anal fistulae. The average duration of evolution of fistulae was 20 years. One case had underwent a proctologic surgical intervention 2 years before presentation. The cases complained of chronic anal pain (two cases), progressive fistulisation (a single case), weight loss (a single case) and constipation in (a single case). Clinical examination revealed multiple fistulae in two cases (Figs. 1 and 2). Buttocks were deformed in two cases and the anal margin ⇑ Corresponding author. Tel.: +212 664477558. E-mail address: [email protected] (A. Diffaa).

was deformed in one case. Perianal ulceration and hypotonic anal sphincter were present each in one case. No inguinal lymphadenopathy was noted. Rectal digital examination revealed an infiltration of retro-rectal space in one case, anal infiltration in two cases and a mucinous secretion simulating ‘cooked grains of tapioca’ in two cases. Colonoscopy was normal in all cases. Histopathological examination of lesions revealed a colloid aspect with mucous puddle pool (Fig. 3), and the immunohistochemical study revealed (CK7 positive/CK20 negative) in all cases (Fig. 3). Computed tomography (CT) showed a collection in the ischioanal space in one case (Fig. 4) and the retro-rectal space in another case. Thickening of the anal and the lower rectal wall were noted in two cases (Fig. 5). All lesions fistulised onto the skin. CT showed a tumourous invasion of prostatic lodge in one case and multiple hepatic and pulmonary metastases in another case. Anoperineal resection was suggested and only one case underwent this surgery, the others cases refused all therapeutic options and were lost to follow up. The patient who underwent surgery has 24 months of follow-up without locoregional recurrence. Discussion Primary mucinous adenocarcinoma of the anus is a rare malignancy (3–11% of all of the anal carcinomas) [1]. Its epidemiology is unknown. To our knowledge, no study has analysed the risk factors of this tumour, and publications point to the association with

1687-1979/$ - see front matter Ó 2010 Arab Journal of Gastroenterology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ajg.2010.12.001

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A. Diffaa et al. / Arab Journal of Gastroenterology 12 (2011) 48–50 Table 1 Characteristics of the cases. Case

Sex/ age (years)

Antecedents

Symptoms

1

M 70

Anal fistula 22 years

Anal pain 4 months

2

M 75

Anal fistula 18 years Fistula surgery 2 years

Anal pain 3 months

3

M 59

Anal fistulae 20 years

– New fistulae – Terminal constipation – Weight loss 4 months

Examination

– Multiple fistulae with indurations – Infiltration of anococcygien space and the anus – Perianal ulceration – Mucus secretion – Low sphincterien tonus – Anal formation – Anal infiltration – Mucinous secretion

Immunohistochemical profile

Computed tomography

Treatment

Survival

(CK7+/CK20 )

– Ischioanal space collection – Skin fistulisation

APA

24 months

(CK7+/CK20 )

– Retro-rectal collection – Anal and the low rectal wall thickening

–

–

(CK7+/CK20 )

– Anorectal infiltration – Skin fistulisation - infiltration of prostatic lodge and the perineum – Liver and pulmonary metastases

–

–

APA: Abdominoperineal amputation.

chronic inflammatory states (abscesses and anal fistulae) of a duration exceeding 10 years [1,2]. The pathogenesis of anal adenocarcinoma is much debated. Usually, the anal transition zone (ATZ) is located between the lieberkuehn rectal epithelium and the non-keratinized malpighian

epithelium. This zone has a variable surface and includes the anal glands of Hermann and Desfoss [3]. The epithelium of ATZ contains small islands of both epithelia, which can give rise to an adenocar-

Fig. 3. Tumourous proliferation with focus of mucosecretions PAS positive (HE, G 100). Fig. 1. Tumourous polyfistulous area with deformation of the buttocks.

Fig. 2. Anal margin infiltration by the tumoural process.

Fig. 4. Bilateral ischioanal space collection with anal wall thickness.

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A. Diffaa et al. / Arab Journal of Gastroenterology 12 (2011) 48–50

Fig. 5. Rectal wall thickness with retro-rectal collection.

cinoma from the lieberkuhn islands, anal glands, epithelium of the ATZ itself and wall of the chronic fistulae [3]. The difficulty to locate the point of origin of these tumours was resolved by analysing keratins and mucins by immunohistochemical study. The adenocarcinoma of rectum originating from the epithelium of the higher part of the anus or the small lieberkuhn islands of the ATZ has an immunohistochemical profile of (CK7 negative/CK20 positive). The adenocarcinoma rising from the ATZ of anal glands or the epithelium of ATZ would provide a histological feature with a colloid aspect with mucous puddle pools and a profile of keratin and mucin identical to that of the epithelium of anal glands (CK7 positive/ CK20 negative) [1,4,5], and this is the only profile we had in our study. Finally, adenocarcinoma originating from the wall of chronic anal fistulae or those spontaneously fistulised would give a profile of (CK7 positive/CK20 positive) [3]. Other particular cases of mucinous adenocarcinomas were reported in the literature as malignant transformation of anoperineal Crohn’s disease in 0.7% of the cases [6], anal metastasis of other adenocarcinomas and malignant transformation of rectal malformations [7,8]. These malformations would occur in 7–10% of the cases [1,4,9]. The colonoscopy in the search of a synchronous colorectal tumour must be systematic [1]. The metachronous metastasis can appear like a primary anal cancer [1]. The diagnosis of anal mucinous adenocarcinoma presents two major problems; first is the difficulty of an early diagnosis because of the atypical lesions as illustrated in our cases; second is a therapeutic problem due to the advanced stages of disease at presentation as in two of our cases [10]. The clinical manifestations of adenocarcinoma are not specific. In the series reported by Kline et al., the patients were asymptomatic in 15% of the cases [11]. Generally, patients suffering from a fistula for over 10 years or recurring fistula even after surgery should be alarming. The clinical presentation could be an anal abscess or a bulky perineal lesion (80% of cases) [2,3]. The macroscopic features of the lesions are misleading, and would generally be a complex fistula with budding and/or cicatricial external openings. In the presence of a hard wall of the fistula or of the abscess, the malignant character of the lesion should be suspected [1,3,5]. The fistula would discharge a mucinous secretion simulating ‘cooked grains of tapioca’ that should suggest the diagnosis [1,3,5]. The inguinal nodes should be examined. Some differential diagnoses were reported: Squamous cell carcinoma, apocrine carcinoma and perianal Paget disease. Histopathology can differentiate these lesions from each other [9]. Imaging studies may be used to assess the locoregional extension and distant metastasis [12]. Endoanal sonography would reveal a hyperechoic and heterogeneous lesion, similar to the

ovarian microcystic mucinous tumours [6,10]. Magnetic resonance imaging may also provide information about the locoregional extension and discover ignored fistula missed by clinical examination or endosonography [9]. The histological diagnosis of anal mucinous adenocarcinoma is based on microscopic study; only the surgical resection examined by an experienced pathologist guarantees an accurate diagnosis of the tumour [3]. There is no general agreement about the management of anal mucinous adenocarcinoma [13]. Radical surgery as the abdominoperineal resection is, however, the treatment of choice and the only curative option [2–4,13]. The combination of radiotherapy and chemotherapy with surgery was used by different groups with disappointing results in the locally advanced cases [4]. The prognosis of this tumour is poor [2,3,9]. The 5-year survival is between 4.8% [3,4] and 17% [14]. In the oldest series, the 5-year survival after radical surgery was 5% and these results improved in the recent series to 80% [8] and 93% [9] at 3 years [3]. Prevention of disease consists of resection of any fistulae or perianal induration and the treatment of rectal malformations and perianal lesions of Crohn’s disease. The regular postoperative follow-up consists of the clinical examination with anal endosonography. In conclusion, mucinous adenocarcinoma of the anus is a rare malignancy. In our case, the clinical profile was that of a patient with a painful or complex chronic fistula (>20 years). The clinical presentation is often misleading. In all cases, the adenocarcinoma is growing from ATZ epithelium. Currently, the abdominoperineal resection is the only curative therapy with a relatively long survival for early cases. Conflict of interest The authors declared that there was no conflict of interest. References [1] Schaffzin DM, Stahl TJ, Smith LE. Perianal mucinous adenocarcinoma: unusual case presentations and review of the literature. Am Surg 2003;69(2):166–9. [2] Ibanez J, Erro JM, Aranda F, et al. Adenocarcinoma mucinoso en fistula perianal de largo tiempo de evolucion tratado mediante QT-RT neoadyuvante y amputacion abdominoperineal laparoscopica [Mucinous adenocarcinoma on chronic perianal fistula treated by neoadjuvant chemoradiotherapy and laparoscopy-assisted abdominoperineal amputation]. Cir Esp 2006;79(3):184–5. [3] Marti L, Nussbaumer P, Breitbach T, et al. Das perianale mucinose adenocarcinom. Ein weiterer grund fur die histologische untersuchung bei analfistel oder anorectalabscess [Perianal mucinous adenocarcinoma. A further reason for histological study of anal fistula or anorectal abscess]. Chirurgia 2001;72(5):573–7. [4] Nishimura T, Nozue M, Suzuki K, et al. Perianal mucinous carcinoma successfully treated with a combination of external beam radiotherapy and high dose rate interstitial brachytherapy. Br J Radiol 2000;73(870):661–4. [5] Papapolychroniadis C, Kaimakis D, Giannoulis K, et al. A case of mucinous adenocarcinoma arising in long-standing multiple perianal and presacral fistulas. Tech Coloproctol 2004;8(Suppl. 1):S138–40. [6] Mates IN, Dinu D, Radulescu G, et al. Carcinom coloid infiltrativ grefat pe supuratie cronica ano-rectala; dificultati de diagnostic si tratament chirurgical [Infiltrating mucinous carcinoma developed on chronic anal fistula; diagnostic and surgical difficulties]. Chirurgia (Bucur) 2003;98(5):459–64. [7] Jensen SL, Shokouh Amiri MH, Hagen K, et al. Adenocarcinoma of the anal ducts. A series of 21 cases. Dis Colon Rectum 1988;31(4):268–72. [8] Abel ME, Chiu YS, Russell TR, et al. Adenocarcinoma of the anal glands. Results of a survey. Dis Colon Rectum 1993;36(4):383–7. [9] Behan WM, Burnett RA. Adenocarcinoma of the anal glands. J Clin Pathol 1996;49(12):1009–11. [10] Navarra G, Ascanelli S, Turini A, et al. Mucinous adenocarcinoma in chronic anorectal fistula. Chir Ital 1999;51(5):413–6. [11] Kline RJ, Spencer RJ, Harrison Jr EG. Carcinoma associated with fistula-in-ano. Arch Surg 1964;89:989–94. [12] Hama Y, Makita K, Yamana T, et al. Mucinous adenocarcinoma arising from fistula in ano: MRI findings. Am J Roentgenol 2006;187(2):517–21. [13] Ball CS, Wujanto R, Haboubi NY, et al. Carcinoma in anal Crohn’s disease: discussion paper. J R Soc Med 1988;81(4):217–9. [14] Merlini M, Eckert P. Malignant tumors of the anus. A study of 106 cases. Am J Surg 1985;150(3):370–2.