|Year : 2017 | Volume
| Issue : 5 | Page : 488-491
Gastrointestinal stromal tumor of the anal canal: An unusual presentation
Chhanda Das1, Madhumita Mukhopadhyay1, Madhu Kumari1, Bikram Halder2
1 Department of Pathology, IPGME and R, Kolkata, West Bengal, India
2 Department of Surgery, IPGME and R, Kolkata, West Bengal, India
|Date of Submission||06-Dec-2016|
|Date of Acceptance||19-Apr-2017|
|Date of Web Publication||14-Nov-2017|
31, Eastern Park, First Road, Santoshpur, Kolkata - 700 075, West Bengal
Source of Support: None, Conflict of Interest: None
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common site is stomach, followed by small intestine, colon, and esophagus. However, GIST from the anal canal is an extremely rare tumor. Here, we report an extremely rare case of GIST of the anal canal in a 40-year-old female with a history of irregular bowel habits mixed with blood and constipation for 4 months. Diagnosis was made on the basis of histopathological and immunohistochemical examination.
Keywords: Anal canal, C-KIT, DOG1, gastrointestinal stromal tumor
|How to cite this article:|
Das C, Mukhopadhyay M, Kumari M, Halder B. Gastrointestinal stromal tumor of the anal canal: An unusual presentation. Med J DY Patil Univ 2017;10:488-91
|How to cite this URL:|
Das C, Mukhopadhyay M, Kumari M, Halder B. Gastrointestinal stromal tumor of the anal canal: An unusual presentation. Med J DY Patil Univ [serial online] 2017 [cited 2019 Aug 25];10:488-91. Available from: http://www.mjdrdypu.org/text.asp?2017/10/5/488/218188
| Introduction|| |
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal (GI) tract. The most common site is stomach (50%–60%), followed by small intestine (30%–40%), colon (7%), and esophagus (1%). Due to the rarity of both rectal and anal GIST, they are often grouped together as anorectal stromal tumors representing the 5% of all GIST. However, of these, GIST from anal canal represents only 2%–8%, making it an extremely rare tumor. Our case is an anorectal mass starting from the anus and extending up to the rectum.
| Case Report|| |
A 40-year-old female presented with pain during defecation and occasional bleeding per rectum over 2 months. She had anorexia and weight loss for the last 2 months. Her general survey was normal apart from pallor and weakness. On digital rectal examination, a mass was felt about 4 cm from anal verge involving the anterior wall of the rectum. The upper border of the mass could not be reached. No inguinal, iliac, para-aortic, or supraclavicular lymph nodes were palpable. Her biochemical parameters were all within normal limits. Computed tomography scan of the whole abdomen showed a large proliferating anorectal mass [Figure 1]. Her colonoscopy was suggestive of an ulceroproliferative growth starting 3–8 cm from anal verge involving one-third of the luminal surface in the anterior wall. In colonoscopy-guided biopsy, the histomorphology was suggestive of spindle cell lesion possibility of GIST. The patient underwent abdominoperineal resection (APR) with end colostomy [Figure 2]. Specimen after surgery was sent to the pathology department for histopathological examination, the measurement of total specimen of sigmoid colon, rectum, anal canal and posterior vaginal wall is 25 × 8 × 5cm. Growth is identified at anal canal measuring 7 × 4 × 4 cm [Figure 3]. Cut section showed necrotic, variegated appearance. On microscopic examination, it showed tumor mass composed of cells arranged in interlacing fascicles. Individual cells are spindle shaped with cigar-shaped nuclei. Mitotic activity >5/50 high power field (hpf) is seen. Nuclear pleomorphism is also seen. Features are suggestive of GIST [Figure 4] and [Figure 5]. Both margins of resection were free. Prognostic Group 6a. Grade: Malignant. C-KIT immunostaining was positive (score 3+) [Figure 6]. The DOG1 immunostaining was also positive [Figure 7]. Hence, from histological and immunohistochemical diagnosis, it was confirmed as GIST of the anal canal.
|Figure 1: Computed tomography scan showing large mass involving anal canal|
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|Figure 4: Photomicrograph showing tumor mass composed of interlacing fascicle of spindle cell (H and E, ×100)|
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|Figure 5: Tumor mass composed of spindle cells with cigar-shaped nuclei. Prominent mitotic activity noted (×400)|
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| Discussion|| |
The length of the anal canal is about 4 cm. The anal canal lies between the anal verge (anal orifice) in perineum below and rectum above. In our case, there is an ulceroproliferative growth starting at 3 cm from anal verge and extending up to the rectum. Transitional zone in the anal canal is the dentate or pectinate line. Above this transitional zone, canal is lined by columnar epithelium and below it is lined by squamous epithelium. Tumors occur in the anal canal can be either keratinizing or nonkeratinizing, in relation to the location to the dentate line.
GISTs are derived from interstitial cells of Cajal. These tumors occur due to mutation of C-KIT or platelet-derived growth factor receptor A (PDGFRA) which causes Cajal cell proliferation and GIST. The KIT protein, a proto-oncogene, is a transmembrane tyrosine kinase receptor for a growth factor, and mutation of this gene causes constitutional activation of the kinase ligand.
Mostly, GISTs are spindle cell tumors while epithelioid morphology is also seen in 20%–25% cases. Few cases show mixed histology. Nuclear pleomorphism is rare and occurs more commonly in epithelioid morphology. The most commonly accepted criteria to predict the malignancy of GIST are the mitotic activity (>5 mitotic figures/50 hpf) and the tumor size (>5 cm). In our case, the size of the tumor was 7 cm in maximum dimension. In microscopy, it showed spindle cells arranged in interlacing fascicles having cigar-shaped nuclei with nuclear pleomorphism and >5/50 hpf mitotic figures. Hence, this was a malignant GIST.
These tumors show strong positivity for KIT (CD117) which appears as cytoplasmic, membrane associated, or sometimes as perinuclear dots. Anoctamin-1, a chloride channel protein which is detected by the DOG1 antibody (discovered on GIST1), is highly sensitive and more specific than CD117 for GIST and is associated with both cytoplasmic and membrane staining. Both CD117 and DOG1 are expressed in interstitial cells of Cajal. GIST expresses CD117 in up to 95% of cases, but also CD34 (70%), smooth muscle actin (40%), protein S100 and desmin 2%. However, about 5%–15% of GISTs lack KIT expression and problematic in the diagnosis of GISTs. DOG1 is most useful in KIT-negative tumors (these are more likely to harbor a PDGFRA mutation). The DOG1 has proved to be very sensitive and specific for the diagnosis of GISTs when compared with the C-KIT, including cases of extra-GI and metastatic GIST. Our case was both CD117 and DOG1 positive.
The differential diagnosis of GISTs is schwannoma, Ewing sarcoma, true smooth muscle tumor, spindle cell carcinoma, and epithelial malignancy. These tumors are differentiated by histological pattern and specific immunohistochemistry (IHC).
Surgery is the treatment of choice for GIST. However, there is a controversy between APR and conservative surgery. Although the incidence of local recurrence is lower after APR, there is no improvement in the incidence of distant metastasis and overall survival. Inhibitor of tyrosine kinase receptor imatinib mesylate is used as the target therapy for local or distant recurrence after surgical resection in GIST. The effect of tyrosine-kinase inhibitor is dependent on the exon mutations on the KIT gene. Many studies reported tumor response to imatinib, ranging from 12% to 70% in cases of exon 9 and exon 11 mutations of the C-KIT gene, respectively. Molecularly targeted therapy combined with radiation therapy could improve the outcomes for patients diagnosed with GIST.
| Conclusion|| |
Our case was a case of malignant anal canal GIST with tumor size more than 5 cm in maximum dimension. Mitotic figures were more than 5/50 hpf. The CD117 IHC score was 3+ in spindled cells. Hence, our patient has been put on adjuvant imatinib mesylate 400 mg daily. The differential diagnosis should always be kept in mind before diagnosing the GIST of the anal canal, and it should be confirmed with the help of IHC staining. Close follow-up of patient is necessary for local recurrence or metastases, and prognosis is usually better than carcinomas in this region. CD-117 score is not only diagnostic but also guides adjuvant therapy and is also prognostic marker.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ghobadi A, Kabbani W, Barker B, Dowell JE. Rectal GI stromal tumor mimicking a prostate mass. J Clin Oncol 2007;25:5827-8.
Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumours. Ann Chir Gynaecol 1998;87:278-81.
Li JC, Ng SS, Lo AW, Lee JF, Yiu RY, Leung KL. Outcome of radical excision of anorectal gastrointestinal stromal tumors in Hong Kong Chinese patients. Indian J Gastroenterol 2007;26:33-5.
] [Full text]
Nigri GR, Dente M, Valabrega S, Aurello P, D'Angelo F, Montrone G, et al.
Gastrointestinal stromal tumor of the anal canal: An unusual presentation. World J Surg Oncol 2007;5:20.
Heinrich MC, Blanke CD, Druker BJ, Corless CL. Inhibition of KIT tyrosine kinase activity: A novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 2002;20:1692-703.
Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al.
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-80.
Sabah M, Cummins R, Leader M, Kay E. Altered expression of cell cycle regulatory proteins in gastrointestinal stromal tumors: Markers with potential prognostic implications. Hum Pathol 2006;37:648-55.
West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, et al.
The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165:107-13.
Lopes JM, Gouveia A, Pimenta A. The role of pathological anatomy in the diagnosis and prognosis of GISTs. Rev Port Cir 2007;2:35-8.
Miwa S, Nakajima T, Murai Y, Takano Y, Sugiyama T. Mutation assay of the novel gene DOG1 in gastrointestinal stromal tumors (GISTs). J Gastroenterol 2008;43:531-7.
Fatima N, Cohen C, Siddiqui MT. DOG1 utility in diagnosing gastrointestinal stromal tumors on fine-needle aspiration. Cancer Cytopathol 2011;119:202-8.
Changchien CR, Wu MC, Tasi WS, Tang R, Chiang JM, Chen JS, et al.
Evaluation of prognosis for malignant rectal gastrointestinal stromal tumor by clinical parameters and immunohistochemical staining. Dis Colon Rectum 2004;47:1922-9.
Gold JS, Dematteo RP. Combined surgical and molecular therapy: The gastrointestinal stromal tumor model. Ann Surg 2006;244:176-84.
Nemoto Y, Mikami T, Hana K, Kikuchi S, Kobayashi N, Watanabe M, et al.
Correlation of enhanced cell turnover with prognosis of gastrointestinal stromal tumors of the stomach: Relevance of cellularity and p27kip1. Pathol Int 2006;56:724-31.
Ciresa M, D'Angelillo RM, Ramella S, Cellini F, Gaudino D, Stimato G, et al.
Molecularly targeted therapy and radiotherapy in the management of localized gastrointestinal stromal tumor (GIST) of the rectum: A case report. Tumori 2009;95:236-9.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]