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Year : 2019  |  Volume : 8  |  Issue : 2  |  Page : 61-63

Mixed adenoneuroendocrine tumor of the perianal skin

St. Francis Hospital and Medical Center, Hartford, CT, USA

Date of Web Publication27-Jun-2019

Correspondence Address:
Dr. Daniel J Mullins
St. Francis Hospital and Medical Center, 6 Northwestern Drive #305, Hartford, CT 06002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/WJCS.WJCS_10_19

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Mixed adenoneuroendocrine carcinoma (MANEC) of the intestinal tract, is relatively rare and with a poor prognosis. The majority of literature to date has documented the rare occurrence of this tumor within the colon or rectum, but not within the anal canal or verge. We report our case of a female patient identified with a MANEC tumor of the perianal skin extending into the anal canal.

Keywords: Anal canal, anal verge, mixed adenoneuroendocrine carcinoma, perianal cancer

How to cite this article:
Mullins DJ, Lewis RT. Mixed adenoneuroendocrine tumor of the perianal skin. World J Colorectal Surg 2019;8:61-3

How to cite this URL:
Mullins DJ, Lewis RT. Mixed adenoneuroendocrine tumor of the perianal skin. World J Colorectal Surg [serial online] 2019 [cited 2021 Aug 2];8:61-3. Available from: https://www.wjcs.us.com/text.asp?2019/8/2/61/261543

  Introduction Top

Mixed adenoneuroendocrine carcinoma(MANEC) of the gastrointestinal tract is a significantly rare entity, which was recently classified by the World Health Organization(WHO) in 2010 as a carcinoma with at least 30% of both gland-forming epithelial and neuroendocrine components. There has been a paucity of case reports regarding patients with this diagnosis, with the majority of reported cases present in the upper intestinal tract. We report the first case of a perianal MANEC.

  Case Report Top

A72-year-old female presented with several weeks of perianal pain. She described the pain as sharp, nonradiating, and burning in nature localized to the anal canal. The pain was worsened with sitting. She also noticed painless hematochezia. She denied any weight loss, and there was no mucus or blood mixed in with her stools. She had undergone an upper endoscopy and colonoscopy 1year prior and was noted to have a lipomatous ileocecal valve with no other significant findings. Upper endoscopy revealed GradeA reflux esophagitis, a TypeB Schatzki ring, hiatal hernia, and erosive gastritis and duodenitis, which was treated with a proton pump inhibitor (PPI).

Her other medical problems include hypertension, aortic regurgitation, osteoporosis, and a history of rheumatic fever with a surgical history of a tonsillectomy, hysterectomy with bilateral salpingo-oophorectomy, cholecystectomy, appendectomy, and breast biopsies.

She denied any family history of colon or rectal cancer. Her father died at the age of 95years reportedly from prostate cancer, and she reported a paternal cousin and niece with breast cancer.

On examination, she was found to have a 2.5-cm mass on the perianal skin, 3–4cm from the anal verge with extensive perianal skin thickening and excoriation[Figure 1] and [Figure 2]. An incisional biopsy of the mass was performed which revealed a MANEC tumor of colorectal primary origin. Squamous epithelium containing malignant cells with a variegated appearance forming glands in combination with tumor cells with a basaloid/neuroendocrine appearance was found. The tumor cells stained positive for CK20, CDX2, CD56, synaptophysin, MOC-31, BerEP4, and carcinoembryonic antigen(CEA), but negative for CK7 and chromogranin. Repeat punch biopsies of the surrounding tissue confirmed pagetoid spread of poorly differentiated carcinoma with mixed glandular and neuroendocrine features throughout the perianal skin.
Figure1: Perianal mixed adenoneuroendocrine carcinoma tumor

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Figure2: Mixed adenoneuroendocrine carcinoma tumor

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She was taken to the operating room for mapping biopsies and colonoscopy. Circumferential punch biopsies were performed with occult spread noted anteriorly to the rectovaginal septum. Colonoscopy revealed no malignancy. Preoperative CEA was 4.5ng/mL. Pelvic magnetic resonance imaging(MRI) and positron emission tomography–computed tomography (PET-CT) were performed with findings of a 2.3-cm right perianal infralevator mass with a standardized uptake value of 6.1. She was given neoadjuvant treatment for a Stage II, T2N0M0 tumor with capecitabine and 4500 cGy in 180 cGy fractions of radiation therapy with inclusion of perirectal, pelvic, and bilateral inguinal lymph nodes. Posttreatment MRI and PET-CT were done, indicating partial response and no distant spread of the disease.

Six weeks after neoadjuvant therapy was completed, the patient underwent abdominoperineal resection with en bloc posterior vaginectomy, vertical rectus abdominus myocutaneous flap, and prophylactic Sugarbaker reinforcement of colostomy. Final pathology indicated a 0.5-cm MANEC and T1NO with>1cm negative margins[Figure 3], [Figure 4], [Figure 5].
Figure3: Neuroendocrine differentiated component(brown) and adenocarcinoma component in the left upper quadrant without staining (synaptophysin, ×25)

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Figure4: Cytoplasmic staining of the glandular adenocarcinoma component and not the neuroendocrine component(carcinoembryonic antigen, ×50)

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Figure5: Adenocarcinoma component on the left with neuroendocrine component on the right(HandE, ×50)

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Postoperatively, she developed an early small-bowel obstruction confirmed on CT which required a nasogastric tube and nutritional support via total parental nutrition. Six weeks postoperatively, she underwent lysis of adhesions and small-bowel resection; pathology revealed small-bowel radiation enteritis. Postoperative recovery was uneventful.

Surveillance, using the proton pump inhibitor (PPI) guidelines for rectal cancer, shows no evidence of recurrence 3years after her surgery.

  Discussion Top

To our knowledge, this is the first case report of a MANEC extending from the perianal skin beyond the anal verge into the anal canal. Previous studies have included patients with colon and/or rectal pathology[Table1]. According to the 2010 WHO classification, for a tumor to be defined as a MANEC, both the exocrine and neuroendocrine components must represent at least 30% of the lesion.[1] MANEC contain both malignant gland-forming epithelial and neuroendocrine components. Some tumors contain a mixture of the exocrine and neuroendocrine cancer cells, while in others, the component carcinomas may be separate but contained within the same lesion.[2] Prognosis is related to the grade of malignancy of each component. High-grade malignant MANEC is a neoplasm composed of a tubulovillous or villous adenomatous or carcinomatous adenocarcinoma or squamous cell carcinoma component with a poorly differentiated small-, intermediate-, or large-cell NEC. Our patient presented with two distinct high-grade lesions: an adenocarcinoma with intracellular mucin and a small acinar/tubular growth pattern, and a small-cell NEC. Previous reports have identified other high-gradeMANEC in the colon and rectum. However, these lesions are extremely rare, with about 100cases documented in the literature to date.{Table1}

High-gradeMANEC of colorectal origin favor a macroscopic appearance of a polypoid mass or stenotic lesion with ulceration, with a mean size of 5cm.[3] Pagetoid spread to the perianal skin from and underlying rectal primary has been described.[4] Symptoms are often vague perianal complaints.

Prognosis has been shown to be dependent on the stage and tumor type, with improved survival shown for patients with locoregional versus metastatic disease. Grouped as a whole, gastrointestinal MANECs seem to have a better overall survival compared to pure NECs, although recent studies have shown that purely colorectal MANECs may have a similar survival. Astudy examining the role of each cancer lineage on prognosis found that MANEC with a higher(>50%) neuroendocrine component was associated with worse outcomes.[5]

Currently, there is no well-defined, optimal treatment algorithm for MANEC of the gastrointestinal tract. It has been recommended that treatment should be optimized for more aggressive component of the tumor.[6] Our patient had both poorly differentiated adenocarcinoma and neuroendocrine components with no evidence of metastatic disease. She was treated with neoadjuvant therapy typical of adenocarcinoma with subsequent radical surgery. Currently, 3years after surgery, the patient continues to have no evidence of recurrence. Neoadjuvant therapy, followed by radical surgery to achieve negative margins, should be considered in even high-grade MANEC.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

RindiG, ArnoldR, BosmanFT, CapllaC, KilmstraDS, KloppelG, etal. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: BosmanFT, CarneiroF, HrubanRH, TheiseND, editors. WHO Classification of Tumours of the Digestive System. 4thed. Lyon, France: IARC Press; 2010. p.13-4.  Back to cited text no. 1
La RosaS, MarandoA, SessaF, CapellaC. Mixed adenoneuroendocrine carcinomas(MANECs) of the gastrointestinal tract: An update. Cancers(Basel) 2012;4:11-30.  Back to cited text no. 2
CapellaC, La RosaS, UccellaS, BilloP, CornaggiaM. Mixed endocrine-exocrine tumors of the gastrointestinal tract. Semin Diagn Pathol 2000;17:91-103.  Back to cited text no. 3
EbromP, ParizhD, HajduCH, GadangiP. Paget's disease of the anus masking a mixed adenoneuroendocrine tumour of the rectum. BMJ Case Rep 2017;2017. pii: bcr2016218717.  Back to cited text no. 4
ChenMH, KuoYJ, YehYC, LinYC, TzengCH, LiuCY, etal. High neuroendocrine component is a factor for poor prognosis in gastrointestinal high-grade malignant mixed adenoneuroendocrine neoplasms. JChin Med Assoc 2015;78:454-9.  Back to cited text no. 5
HervieuV, ScoazecJY. Mixed endocrine tumors. Ann Pathol 2005;25:511-28.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1]


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