- Email: [email protected]
Anorectal Malignant Melanomas: Experience of Uludag University
ANORECTAL MALIGNANT MELANOMAS: EXPERIENCE OF ULUDAG UNIVERSITY Berna Aytac,1 Saduman Balaban Adim,1 Omer Yerci,1 and Tuncay Yilmazlar2 Departments of 1Surgical Pathology and 2Surgery, Uludag University Medical School, Bursa, Turkey.
Anorectal melanomas represent a group of mucosal melanomas with unknown etiology and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during clinical examination. We reviewed the morphological and clinical features of 14 anorectal melanomas, and discuss the treatment modalities of this entity. Fourteen patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph node or distant metastasis, treatment modality and survival. Eight patients were female and six were male, and their mean age was 58 years. The size of melanoma ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and spindle cell type tumor in seven and two patients, respectively, whereas, in the remaining seven patients, the tumor was composed of both types. Pigmentation was apparent in all tumors. There was lymph node metastasis in 11 patients and distant metastasis in all patients. Eleven patients underwent abdominoperineal resection and three were treated by local excision. Mean survival was 8.7 months. Prognosis of anorectal melanoma remains poor. Awareness of the diverse clinicopathological features of these lesions, both on the part of the clinicians and pathologists, is crucial for their early detection and proper treatment.
Key Words: anal tumor, malignant melanoma, rectal tumor (Kaohsiung J Med Sci 2010;26:658–62)
Mucosal melanomas account for 0.5–2.0% of all melanomas and anorectal melanomas account for less than 25% of all mucosal melanomas [1–8]. Anorectal melanoma is a rare, lethal neoplasm and frequently arises from melanocytes of the anal squamous zone distal to the dentate line [9–12]. They typically present in the fifth or sixth decade of life and predominantly in woman. Patients have initial local symptoms like rectal bleeding and a changed defecation pattern [1,3–6,12,13]. These symptoms can interfere with benign conditions such as hemorrhoids and polyps. Here, we reviewed the morphological and clinical features of 14 anorectal melanomas.
Received: Apr 28, 2010 Accepted: Aug 31, 2010 Address correspondence and reprint requests to: Dr Berna Aytac, Department of Surgical Pathology, Uludag University Medical School, Bursa 16059, Turkey. E-mail: [email protected]
658
METHODS The clinical and pathological records of 14 patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were reviewed. The clinical features of the patients at the time of admission and follow-up information were obtained from hospital records or directly from the patients’ families. Patients were evaluated with regard to age, sex, histopathological findings, treatment modality and survival. We defined survival as the time that elapsed between initial diagnosis and death attributable to carcinoma. Histopathological findings were obtained from surgically resected specimens from files in the Department of Pathology. Histological sections of formalin-fixed, paraffin-embedded material stained with hematoxylin and eosin were reviewed to assess tumor size, cell type, pigmentation and lymph node or distant metastasis. Tumor cells were classified as epithelioid, lymphoma-like, spindle cell, or Kaohsiung J Med Sci December 2010 • Vol 26 • No 12 © 2010 Elsevier. All rights reserved.
Anorectal melanoma Table. Clinical and pathological features of cases Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Age (yr)/ Size Symptom sex (cm) 70/F 55/M 66/F 60/F 43/M 55/F 66/F 63/M 52/M 27/M 67/F 75/M 73/F 61/F
B, P M, P M C B, P B, M M B M, P B M M B, P B, C, M
3×3×2 5 × 5 × 2.5 4×4×1 5×5×3 5 × 5 × 2.5 3×2×2 3 × 3 × 2.5 7×6×3 6×6×5 8 × 5.5 × 3.5 3×2×2 3×3×2 5×4×3 3×3×2
Cell LN Distant Pigment type metastasis metastasis E E E+S E+S E S E+S E E E+S S E E E+S
+ + + + + + + + + + + + + +
+ + + + + + + + − + + − − +
Brain Brain Liver Brain, lung Brain, liver Liver Liver, lung Brain Brain, liver Brain, lung Liver Brain Liver Brain, lung
Treatment APR APR APR + RT – APR + CT + RT LE + CT APR + CT + RT APR APR + CT + RT APR + CT + RT LE LE APR APR + CT
Follow-up Survey outcome (mo) DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD
9 4 10 5 6 29 13 3 3 4 13 12 13 3
LN = lymph node; B = bleeding; P = Pain; E = Epithelioid; APR = abdominoperineal resection; DOD = died of disease; M = mass; S = spindle; RT = radiotherapy; C = change in bowel habits; CT = chemotherapy; LE = local excision.
pleomorphic. Pigmentation was graded as present or absent. The treatment modality was based both on the clinical stage that was assessed by digital rectal examination and surgeons’ preference.
RESULTS The clinical features at initial diagnosis and follow-up for all 14 cases are given in the Table. The mean age was 58 years (range, 27–75 years). Eight patients were female and six were male. The most common presentation was rectal bleeding (7 cases), followed by pain (5 cases), changes in bowel habits (2 cases), and anal mass (8 cases). The size of melanoma ranged from 3 cm to 8 cm (mean = 4.4 cm). All patients were diagnosed preoperatively with malignant melanoma by colonoscopic biopsy. Eleven patients were treated with abdominoperineal resection (APR) and three with local excision (LE). There was lymph node metastasis in 11 patients and distant metastasis in all patients; liver and brain were the most affected sites. Seven patients received adjunctive therapy including radiotherapy and chemotherapy. All patients died of the disease during follow-up. Mean survival was 8.7 months (range, 3–29 months). Histopathologically, two cell types were observed: epithelioid and spindle cell. Pathological evaluation revealed epithelioid and spindle cell type tumor in Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
seven and two patients, respectively, whereas, in the remaining seven patients, tumor was composed of both cell types. Lymphoma-like or pleomorphic type was not encountered. Epithelioid-type tumor cells usually formed granular cytoplasm, and enlarged, irregular and often angulated nuclei. Nuclear membranes were irregularly thickened with vesicular chromatin. Nucleoli were large and often eosinophilic (Figure A). Spindle tumor cells generally did not display vesicular chromatin patterns or prominent nucleoli. They had enlarged, elongated, somewhat angulated nuclei with diffuse hyperchromasia (Figure B). Pigmentation was apparent in all tumors. The malignant cell population showed strong and diffuse immunohistochemical staining for S-100 protein in all cases (Figure C). The majority of cases stained with HMB-45, although there was greater variability in the strength and distribution (Figure D).
DISCUSSION Melanocytes migrate as neuroectodermal derivatives in the ectodermally-derived mucosa, and can be found in the mucous membranes of the upper aerodigestive (mouth, nose, and paranasal sinuses), gastrointestinal (anorectum, esophagus, stomach and gallbladder), and urogenital (vagina, penis and urethra) tracts [1,10,14–17]. Some of these cells show an age-related increase, with a large number of them being found at 659
B. Aytac, S.B. Adim, O. Yerci, and T. Yilmazlar A
B
C
D
Figure. Tumors demonstrated considerable morphological variability, including (A) epithelioid type and (B) spindle cell type (hematoxylin and eosin; original magnification, 200×). Immunohistochemical evaluation demonstrated strong staining for (C) S–100 and (D) HMB–45 (original magnification, 400×).
or beyond the seventh decade of life in both sexes [12,18]. These cells give rise to malignant melanomas of the mucous membranes. Although both cutaneous and extracutaneous melanomas arise from transformed melanocytes, they differ substantially in clinicopathological and molecular aspects. This probably reflects the lack of association with sun damage, family history, familial predisposition, genes, and precursor nevi in extracutaneous melanomas [1,12,19,20]. Contrary to cutaneous melanomas that usually disseminate to regional lymph nodes, extracutaneous melanomas disseminate hematogenously to the liver, skin, lung and brain [12]. This frequent vascular invasion is associated with tumor necrosis, aggressive behavior and poor prognosis [12]. Das et al reported that most patients (48/72; 66%) presented with distant metastases. Nineteen patients (19/24) had positive lymph node disease, and the mean disease-free survival in these patients was 10.3 months. Disease-free 660
survival in the node-negative patients was 26.5 months [21]. Patients present with rectal bleeding, painful defecation, change in bowel habits and pigmented or non-pigmented polypoid masses that prolapse through the anal verge, with the same presentation as hemorrhoids [9,12]. The tumor is frequently mistaken for benign conditions such as hemorrhoids or rectal polyps [22,23]. Magnetic resonance imaging and endoscopic ultrasonography have been shown to be useful in making an earlier and more accurate diagnosis [22,23]. On computed tomography scans, anal melanoma appears as a bulky, intraluminal fungating mass in the distal rectum, which focally expands and obscures the lumen without causing obstruction, with perirectal infiltration and frequently enlarged lymph nodes [22,23]. The ideal treatment for anorectal melanoma remains controversial, with 90% of patients dying Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
Anorectal melanoma
irrespective of the surgical approach or adjuvant radiotherapy and chemotherapy [12]. The role of adjuvant radiotherapy, immunotherapy and chemotherapy in this disease has not been established. Adjuvant therapies have been used after surgical resection in some studies, with no strong evidence of improvement in outcome [4,24]. Surgical treatment of this specific tumor has a wide spectrum that varies from conservative treatment such as LE, to radical operations such as APR. [4–8,19,25]. In a review that included 17 large case series, Yap et al compared the survival of patients who underwent APR or LE. The analysis revealed no statistically significant difference between two treatment modalities, even at all stages of the disease [26]. Moozar et al reported a better survival rate in patients who underwent wide excision when compared with LE in a study of 14 patients [27]. In our study, 11 patients underwent APR and three were treated by LE, but there was no difference with respect to survival in both groups. These non-cutaneous malignant melanomas are rare tumors with aggressive behavior and dismal outcome [1,11]. The prognosis of patients is poor: the 5-year survival rate is estimated at between 6% and 22% [3,28,29]. The median survival of patients with anorectal melanomas in the United States is 10 months for those with distant metastasis, 13 months for those with regional spread, and 34 months for those with localized disease [28]. Twenty to sixty-two percent of patients with anorectal melanomas have metastatic disease at the time of initial diagnosis as a result of the rich lymphatic system of the anorectal region [12,30]. The tumor can disseminate after a latent period of 2–20 years to several sites such as lymph nodes, bone, lungs, liver, spleen, gastrointestinal tract, kidneys, adrenal glands and subcutaneous tissue [1,11]. The most important prognostic indicators in anorectal melanoma include age, sex, size, anatomic site, stage of disease, duration of symptoms, nodal involvement and molecular markers like proliferating cell nuclear antigen and Ki67 [6]. The Clark level and Breslow indexes that are used for evaluation of cutaneous malignant melanomas are not applicable to extracutaneous malignant melanomas [12]. However, tumor thickness seems to be a strong predictive factor for the risk of local recurrences, as reported by Ballo et al in 2002 [31]. In this respect, anorectal melanoma seems to be similar to cutaneous melanoma, for which tumor thickness is used to plan therapeutic procedures. Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
Invasion into the submucosa gives the tumor cells access to lymphovascular channels, which help in their dissemination [6]. Owing to the rarity of the tumor and its histological variability, misdiagnosis is common; particularly in amelanotic cases with unusual morphological features that can be mistaken for lymphoma, carcinoma, and/or sarcoma [13]. Histologically, the tumor can mimic adenocarcinoma, small cell carcinoma and sarcoma, and the lesion often mimics hemorrhoids [29]. In conclusion, anorectal melanoma is a rare and challenging disease. It affects mostly older patients and has a female predominance. It differs from cutaneous melanoma with regard to risk. The preoperative staging has an important role in influencing treatment decisions, however, according to our experience, the type of surgery does not alter the natural history of this disease. Quality of life needs to be considered when making treatment decisions.
REFERENCES 1.
van Schaik PM, Ernst MF, Meijer HA, et al. Melanoma of the rectum: a rare entity. World J Gastroenterol 2008; 14:1633–5. 2. Ahmad M, Mamoon N, Khan AH. Anorectal melanoma in northern Pakistan. J Pak Med Assoc 1992;42:155–7. 3. Sashiyama H, Takayama W, Miyazaki S, et al. The diagnostic value of endoscopic ultrasonography and magnetic resonance imaging for anorectal malignant melanoma: report of a case. Surg Today 2003;33:209–13. 4. Homsi J, Garrett C. Melanoma of the anal canal: a case series. Dis Colon Rectum 2007;50:1004–10. 5. Ishizone S, Koide N, Karasawa F, et al. Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases. Int J Colorectal Dis 2008;23:1257–62. 6. Ramakrishnan AS, Mahajan V, Kannan R. Optimizing local control in anorectal melanoma. Indian J Cancer 2008;45:13–9. 7. Belli F, Gallino GF, Lo Vullo S, et al. Melanoma the anorectal region the experience of the National Cancer Institute of Milano. Eur J Surg Oncol 2008;3:1–6. 8. Nakamura T, Ide H. Malignant melanoma of the alimentary tract. Gan to Kagaku Ryoho 2003;30:619–25. 9. Vaillant F, Salmon RJ, Rousseau J, et al. Malignant melanoma of the anal canal. Gastroenterol Clin Biol 1983; 7:228–9. 10. DeMatos P, Tyler DS, Seigler HF. Malignant melanoma of the mucous membranes: a review of 119 cases. Ann Surg Oncol 1998;5:733–42. 11. Clemmensen OJ, Fenger C. Melanocytes in the anal canal epithelium. Histopathol 1991;18:237–41.
661
B. Aytac, S.B. Adim, O. Yerci, and T. Yilmazlar 12. Hussein MR. Extracutaneous malignant melanomas. Cancer Invest 2008;26:516–34. 13. Chute DJ, Cousar JB, Mills SE. Anorectal malignant melanoma: morphologic and immunohistochemical features. Am J Clin Pathol 2006;126:93–100. 14. DeMatos P, Tyler DS, Seigler HF. Malignant melanoma of the mucous membranes: a review of 119 cases. Ann Surg Oncol 1998;5:733–42. 15. Piura B. Management of primary melanoma of the female urogenital tract. Lancet Oncol 2008;9:973–81. 16. Patrick RJ, Fenske NA, Messina JL. Primary mucosal melanoma. J Am Acad Dermatol 2007;56:828–34. 17. Werdin C, Limas C, Knodell RG. Primary malignant melanoma of the rectum. Evidence for origination from rectal mucosal melanocytes. Cancer 1988;61:1364–70. 18. Sanchez AA, Wu TT, Prieto VG, et al. Comparison of primary and metastatic malignant melanoma of the esophagus: clinicopathologic review of 10 cases. Arch Pathol Lab Med 2008;132:1623–9. 19. Zhong J, Zhou JN, Xu FP, et al. Diagnosis and treatment of anorectal malignant melanoma—a report of 22 cases with literature review. Ai Zheng 2006;25:619–24. 20. Tomicic J, Wanebo HJ. Mucosal melanomas. Surg Clin North Am 2003;83:237–52. 21. Das G, Gupta S, Shukla PJ, et al. Anorectal melanoma: a large clinicopathologic study from India. Int Surg 2003;88:21–4. 22. Solaz Moreno E, Vallalta Morales M, Silla Búrdalo G, et al. Primary melanoma of the rectum: an infrequent
662
23.
24.
25.
26.
27.
28.
29.
30.
31.
neoplasia with an atypical presentation. Clin Transl Oncol 2005;7:171–3. Biyikoglu I, Oztürk ZA, Köklü S, et al. Primary anorectal malignant melanoma: two case reports and review of the literature. Clin Colorectal Cancer 2007;6:532–5. Stroh C, Manger T. Primary amelanotic anorectal melanoma—a case report. Zentralbl Chir 2007;132: 560–3. Helmke BM, Otto HF. Anorectal melanoma. A rare and highly malignant tumor entity of the anal canal. Pathologe 2004;25:171–7. Yap LB, Neary P. A comparison of wide local excision with abdominoperineal resection in anorectal melanoma. Melanoma Res 2004;14:147–50. Moozar KL, Wong CS, Couture J. Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both. Can J Surg 2003;46:345–9. Podnos YD, Tsai NC, Smith D, et al. Factors affecting survival in patients with anal melanoma. Am Surgeon 2006;72:917–20. Maqbool A, Lintner R, Bokhari A, et al. Anorectal melanoma—3 case reports and a review of the literature. Cutis 2004;73:409–13. Pello MJ, Chang O, Camishion RC. Malignant melanoma of the anal canal. J Med Soc N J 1983;80: 42–3. Weyandt GH, Becker JC. Prognostic factors and therapy for primary anorectal melanoma. Int J Colorectal Dis 2006;21:488–9.
Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
Anorectal melanomas represent a group of mucosal melanomas with unknown etiology and poor prognosis. The lesions can be misdiagnosed as hemorrhoids during clinical examination. We reviewed the morphological and clinical features of 14 anorectal melanomas, and discuss the treatment modalities of this entity. Fourteen patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were evaluated with regard to age, sex, size, morphology, lymph node or distant metastasis, treatment modality and survival. Eight patients were female and six were male, and their mean age was 58 years. The size of melanoma ranged from 3 cm to 8 cm. Pathological evaluation revealed epithelioid and spindle cell type tumor in seven and two patients, respectively, whereas, in the remaining seven patients, the tumor was composed of both types. Pigmentation was apparent in all tumors. There was lymph node metastasis in 11 patients and distant metastasis in all patients. Eleven patients underwent abdominoperineal resection and three were treated by local excision. Mean survival was 8.7 months. Prognosis of anorectal melanoma remains poor. Awareness of the diverse clinicopathological features of these lesions, both on the part of the clinicians and pathologists, is crucial for their early detection and proper treatment.
Key Words: anal tumor, malignant melanoma, rectal tumor (Kaohsiung J Med Sci 2010;26:658–62)
Mucosal melanomas account for 0.5–2.0% of all melanomas and anorectal melanomas account for less than 25% of all mucosal melanomas [1–8]. Anorectal melanoma is a rare, lethal neoplasm and frequently arises from melanocytes of the anal squamous zone distal to the dentate line [9–12]. They typically present in the fifth or sixth decade of life and predominantly in woman. Patients have initial local symptoms like rectal bleeding and a changed defecation pattern [1,3–6,12,13]. These symptoms can interfere with benign conditions such as hemorrhoids and polyps. Here, we reviewed the morphological and clinical features of 14 anorectal melanomas.
Received: Apr 28, 2010 Accepted: Aug 31, 2010 Address correspondence and reprint requests to: Dr Berna Aytac, Department of Surgical Pathology, Uludag University Medical School, Bursa 16059, Turkey. E-mail: [email protected]
658
METHODS The clinical and pathological records of 14 patients who were diagnosed with anorectal malignant melanoma between 1997 and 2004 were reviewed. The clinical features of the patients at the time of admission and follow-up information were obtained from hospital records or directly from the patients’ families. Patients were evaluated with regard to age, sex, histopathological findings, treatment modality and survival. We defined survival as the time that elapsed between initial diagnosis and death attributable to carcinoma. Histopathological findings were obtained from surgically resected specimens from files in the Department of Pathology. Histological sections of formalin-fixed, paraffin-embedded material stained with hematoxylin and eosin were reviewed to assess tumor size, cell type, pigmentation and lymph node or distant metastasis. Tumor cells were classified as epithelioid, lymphoma-like, spindle cell, or Kaohsiung J Med Sci December 2010 • Vol 26 • No 12 © 2010 Elsevier. All rights reserved.
Anorectal melanoma Table. Clinical and pathological features of cases Case 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Age (yr)/ Size Symptom sex (cm) 70/F 55/M 66/F 60/F 43/M 55/F 66/F 63/M 52/M 27/M 67/F 75/M 73/F 61/F
B, P M, P M C B, P B, M M B M, P B M M B, P B, C, M
3×3×2 5 × 5 × 2.5 4×4×1 5×5×3 5 × 5 × 2.5 3×2×2 3 × 3 × 2.5 7×6×3 6×6×5 8 × 5.5 × 3.5 3×2×2 3×3×2 5×4×3 3×3×2
Cell LN Distant Pigment type metastasis metastasis E E E+S E+S E S E+S E E E+S S E E E+S
+ + + + + + + + + + + + + +
+ + + + + + + + − + + − − +
Brain Brain Liver Brain, lung Brain, liver Liver Liver, lung Brain Brain, liver Brain, lung Liver Brain Liver Brain, lung
Treatment APR APR APR + RT – APR + CT + RT LE + CT APR + CT + RT APR APR + CT + RT APR + CT + RT LE LE APR APR + CT
Follow-up Survey outcome (mo) DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD DOD
9 4 10 5 6 29 13 3 3 4 13 12 13 3
LN = lymph node; B = bleeding; P = Pain; E = Epithelioid; APR = abdominoperineal resection; DOD = died of disease; M = mass; S = spindle; RT = radiotherapy; C = change in bowel habits; CT = chemotherapy; LE = local excision.
pleomorphic. Pigmentation was graded as present or absent. The treatment modality was based both on the clinical stage that was assessed by digital rectal examination and surgeons’ preference.
RESULTS The clinical features at initial diagnosis and follow-up for all 14 cases are given in the Table. The mean age was 58 years (range, 27–75 years). Eight patients were female and six were male. The most common presentation was rectal bleeding (7 cases), followed by pain (5 cases), changes in bowel habits (2 cases), and anal mass (8 cases). The size of melanoma ranged from 3 cm to 8 cm (mean = 4.4 cm). All patients were diagnosed preoperatively with malignant melanoma by colonoscopic biopsy. Eleven patients were treated with abdominoperineal resection (APR) and three with local excision (LE). There was lymph node metastasis in 11 patients and distant metastasis in all patients; liver and brain were the most affected sites. Seven patients received adjunctive therapy including radiotherapy and chemotherapy. All patients died of the disease during follow-up. Mean survival was 8.7 months (range, 3–29 months). Histopathologically, two cell types were observed: epithelioid and spindle cell. Pathological evaluation revealed epithelioid and spindle cell type tumor in Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
seven and two patients, respectively, whereas, in the remaining seven patients, tumor was composed of both cell types. Lymphoma-like or pleomorphic type was not encountered. Epithelioid-type tumor cells usually formed granular cytoplasm, and enlarged, irregular and often angulated nuclei. Nuclear membranes were irregularly thickened with vesicular chromatin. Nucleoli were large and often eosinophilic (Figure A). Spindle tumor cells generally did not display vesicular chromatin patterns or prominent nucleoli. They had enlarged, elongated, somewhat angulated nuclei with diffuse hyperchromasia (Figure B). Pigmentation was apparent in all tumors. The malignant cell population showed strong and diffuse immunohistochemical staining for S-100 protein in all cases (Figure C). The majority of cases stained with HMB-45, although there was greater variability in the strength and distribution (Figure D).
DISCUSSION Melanocytes migrate as neuroectodermal derivatives in the ectodermally-derived mucosa, and can be found in the mucous membranes of the upper aerodigestive (mouth, nose, and paranasal sinuses), gastrointestinal (anorectum, esophagus, stomach and gallbladder), and urogenital (vagina, penis and urethra) tracts [1,10,14–17]. Some of these cells show an age-related increase, with a large number of them being found at 659
B. Aytac, S.B. Adim, O. Yerci, and T. Yilmazlar A
B
C
D
Figure. Tumors demonstrated considerable morphological variability, including (A) epithelioid type and (B) spindle cell type (hematoxylin and eosin; original magnification, 200×). Immunohistochemical evaluation demonstrated strong staining for (C) S–100 and (D) HMB–45 (original magnification, 400×).
or beyond the seventh decade of life in both sexes [12,18]. These cells give rise to malignant melanomas of the mucous membranes. Although both cutaneous and extracutaneous melanomas arise from transformed melanocytes, they differ substantially in clinicopathological and molecular aspects. This probably reflects the lack of association with sun damage, family history, familial predisposition, genes, and precursor nevi in extracutaneous melanomas [1,12,19,20]. Contrary to cutaneous melanomas that usually disseminate to regional lymph nodes, extracutaneous melanomas disseminate hematogenously to the liver, skin, lung and brain [12]. This frequent vascular invasion is associated with tumor necrosis, aggressive behavior and poor prognosis [12]. Das et al reported that most patients (48/72; 66%) presented with distant metastases. Nineteen patients (19/24) had positive lymph node disease, and the mean disease-free survival in these patients was 10.3 months. Disease-free 660
survival in the node-negative patients was 26.5 months [21]. Patients present with rectal bleeding, painful defecation, change in bowel habits and pigmented or non-pigmented polypoid masses that prolapse through the anal verge, with the same presentation as hemorrhoids [9,12]. The tumor is frequently mistaken for benign conditions such as hemorrhoids or rectal polyps [22,23]. Magnetic resonance imaging and endoscopic ultrasonography have been shown to be useful in making an earlier and more accurate diagnosis [22,23]. On computed tomography scans, anal melanoma appears as a bulky, intraluminal fungating mass in the distal rectum, which focally expands and obscures the lumen without causing obstruction, with perirectal infiltration and frequently enlarged lymph nodes [22,23]. The ideal treatment for anorectal melanoma remains controversial, with 90% of patients dying Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
Anorectal melanoma
irrespective of the surgical approach or adjuvant radiotherapy and chemotherapy [12]. The role of adjuvant radiotherapy, immunotherapy and chemotherapy in this disease has not been established. Adjuvant therapies have been used after surgical resection in some studies, with no strong evidence of improvement in outcome [4,24]. Surgical treatment of this specific tumor has a wide spectrum that varies from conservative treatment such as LE, to radical operations such as APR. [4–8,19,25]. In a review that included 17 large case series, Yap et al compared the survival of patients who underwent APR or LE. The analysis revealed no statistically significant difference between two treatment modalities, even at all stages of the disease [26]. Moozar et al reported a better survival rate in patients who underwent wide excision when compared with LE in a study of 14 patients [27]. In our study, 11 patients underwent APR and three were treated by LE, but there was no difference with respect to survival in both groups. These non-cutaneous malignant melanomas are rare tumors with aggressive behavior and dismal outcome [1,11]. The prognosis of patients is poor: the 5-year survival rate is estimated at between 6% and 22% [3,28,29]. The median survival of patients with anorectal melanomas in the United States is 10 months for those with distant metastasis, 13 months for those with regional spread, and 34 months for those with localized disease [28]. Twenty to sixty-two percent of patients with anorectal melanomas have metastatic disease at the time of initial diagnosis as a result of the rich lymphatic system of the anorectal region [12,30]. The tumor can disseminate after a latent period of 2–20 years to several sites such as lymph nodes, bone, lungs, liver, spleen, gastrointestinal tract, kidneys, adrenal glands and subcutaneous tissue [1,11]. The most important prognostic indicators in anorectal melanoma include age, sex, size, anatomic site, stage of disease, duration of symptoms, nodal involvement and molecular markers like proliferating cell nuclear antigen and Ki67 [6]. The Clark level and Breslow indexes that are used for evaluation of cutaneous malignant melanomas are not applicable to extracutaneous malignant melanomas [12]. However, tumor thickness seems to be a strong predictive factor for the risk of local recurrences, as reported by Ballo et al in 2002 [31]. In this respect, anorectal melanoma seems to be similar to cutaneous melanoma, for which tumor thickness is used to plan therapeutic procedures. Kaohsiung J Med Sci December 2010 • Vol 26 • No 12
Invasion into the submucosa gives the tumor cells access to lymphovascular channels, which help in their dissemination [6]. Owing to the rarity of the tumor and its histological variability, misdiagnosis is common; particularly in amelanotic cases with unusual morphological features that can be mistaken for lymphoma, carcinoma, and/or sarcoma [13]. Histologically, the tumor can mimic adenocarcinoma, small cell carcinoma and sarcoma, and the lesion often mimics hemorrhoids [29]. In conclusion, anorectal melanoma is a rare and challenging disease. It affects mostly older patients and has a female predominance. It differs from cutaneous melanoma with regard to risk. The preoperative staging has an important role in influencing treatment decisions, however, according to our experience, the type of surgery does not alter the natural history of this disease. Quality of life needs to be considered when making treatment decisions.
REFERENCES 1.
van Schaik PM, Ernst MF, Meijer HA, et al. Melanoma of the rectum: a rare entity. World J Gastroenterol 2008; 14:1633–5. 2. Ahmad M, Mamoon N, Khan AH. Anorectal melanoma in northern Pakistan. J Pak Med Assoc 1992;42:155–7. 3. Sashiyama H, Takayama W, Miyazaki S, et al. The diagnostic value of endoscopic ultrasonography and magnetic resonance imaging for anorectal malignant melanoma: report of a case. Surg Today 2003;33:209–13. 4. Homsi J, Garrett C. Melanoma of the anal canal: a case series. Dis Colon Rectum 2007;50:1004–10. 5. Ishizone S, Koide N, Karasawa F, et al. Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases. Int J Colorectal Dis 2008;23:1257–62. 6. Ramakrishnan AS, Mahajan V, Kannan R. Optimizing local control in anorectal melanoma. Indian J Cancer 2008;45:13–9. 7. Belli F, Gallino GF, Lo Vullo S, et al. Melanoma the anorectal region the experience of the National Cancer Institute of Milano. Eur J Surg Oncol 2008;3:1–6. 8. Nakamura T, Ide H. Malignant melanoma of the alimentary tract. Gan to Kagaku Ryoho 2003;30:619–25. 9. Vaillant F, Salmon RJ, Rousseau J, et al. Malignant melanoma of the anal canal. Gastroenterol Clin Biol 1983; 7:228–9. 10. DeMatos P, Tyler DS, Seigler HF. Malignant melanoma of the mucous membranes: a review of 119 cases. Ann Surg Oncol 1998;5:733–42. 11. Clemmensen OJ, Fenger C. Melanocytes in the anal canal epithelium. Histopathol 1991;18:237–41.
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B. Aytac, S.B. Adim, O. Yerci, and T. Yilmazlar 12. Hussein MR. Extracutaneous malignant melanomas. Cancer Invest 2008;26:516–34. 13. Chute DJ, Cousar JB, Mills SE. Anorectal malignant melanoma: morphologic and immunohistochemical features. Am J Clin Pathol 2006;126:93–100. 14. DeMatos P, Tyler DS, Seigler HF. Malignant melanoma of the mucous membranes: a review of 119 cases. Ann Surg Oncol 1998;5:733–42. 15. Piura B. Management of primary melanoma of the female urogenital tract. Lancet Oncol 2008;9:973–81. 16. Patrick RJ, Fenske NA, Messina JL. Primary mucosal melanoma. J Am Acad Dermatol 2007;56:828–34. 17. Werdin C, Limas C, Knodell RG. Primary malignant melanoma of the rectum. Evidence for origination from rectal mucosal melanocytes. Cancer 1988;61:1364–70. 18. Sanchez AA, Wu TT, Prieto VG, et al. Comparison of primary and metastatic malignant melanoma of the esophagus: clinicopathologic review of 10 cases. Arch Pathol Lab Med 2008;132:1623–9. 19. Zhong J, Zhou JN, Xu FP, et al. Diagnosis and treatment of anorectal malignant melanoma—a report of 22 cases with literature review. Ai Zheng 2006;25:619–24. 20. Tomicic J, Wanebo HJ. Mucosal melanomas. Surg Clin North Am 2003;83:237–52. 21. Das G, Gupta S, Shukla PJ, et al. Anorectal melanoma: a large clinicopathologic study from India. Int Surg 2003;88:21–4. 22. Solaz Moreno E, Vallalta Morales M, Silla Búrdalo G, et al. Primary melanoma of the rectum: an infrequent
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Kaohsiung J Med Sci December 2010 • Vol 26 • No 12