Primary anorectal melanoma: Multimodality management in a series of four cases and review of literature

Nishant Lohia; Manoj Prashar; S Harish; Sankalp Singh; Anand Subramananiam; Sundaram Viswanath; Richa Ranjan; Gaurav Trivedi

doi:10.4103/mjmsr.mjmsr_37_20

CASE REPORT

Year : 2020 | Volume : 11 | Issue : 2 | Page : 91-95

Primary anorectal melanoma: Multimodality management in a series of four cases and review of literature

Nishant Lohia¹, Manoj Prashar¹, S Harish¹, Sankalp Singh¹, Anand Subramananiam², Sundaram Viswanath¹, Richa Ranjan³, Gaurav Trivedi¹
¹ Malignant Disease Treatment Centre, Command Hospital (CC), Lucknow, Uttar Pradesh, India
² Department of Surgery, Armed Forces Medical College, Pune, Maharashtra, India
³ Malignant Disease Treatment Centre, Command Hospital (EC), Kolkata, West Bengal, India

Date of Submission	05-Sep-2020
Date of Acceptance	02-Nov-2020
Date of Web Publication	25-May-2021

Correspondence Address:
Dr. Sankalp Singh
Malignant Disease Treatment Centre, Command Hospital (CC), Lucknow, Uttar Pradesh
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/mjmsr.mjmsr_37_20

Abstract

Anorectal melanoma is a very rare and aggressive mucosal melanocytic malignancy, accounting for 1% of all anorectal cancers. There have only been a few cases reported. Surgical resection remains the mainstay of treatment. No definitive management strategies exist because of the absence of randomized trials. We here report a case series on four cases of anorectal melanoma. All four cases underwent abdominoperineal resection (APR) and nodal dissection. Two out of four cases received adjuvant temozolomide (TMZ), one case received adjuvant doublet chemotherapy with TMZ and cisplatin, and the fourth case succumbed to nononcological disease before he could be subjected to adjuvant chemotherapy. In the first and third case, nodal dissection was limited to pelvic nodes only. However, in the second case, extensive nodal dissection in the form of bilateral pelvic and inguinal lymph nodal dissection and para-aortic lymph nodal dissection was performed. The fourth case also was subjected to extensive nodal dissection in form of bilateral pelvic and para-aortic lymph node dissection. The first patient however became metastatic at the end of first cycle of adjuvant TMZ and succumbed to his illness post 3 months of surgery. The second patient could complete all six cycles of adjuvant TMZ, and after 1 year of completion of adjuvant TMZ, he presented with skeletal and brain metastases. He also received palliative whole-brain radiotherapy for brain metastases. He finally succumbed to his disease 18 months after surgery. The third case completed all six cycles of adjuvant TMZ and is still alive with disease-free interval of around 1 year. The fourth case succumbed to nononcological death around 1 month after surgery.

Keywords: Abdominoperineal resection, anorectum, melanoma, temozolomide

How to cite this article:
Lohia N, Prashar M, Harish S, Singh S, Subramananiam A, Viswanath S, Ranjan R, Trivedi G. Primary anorectal melanoma: Multimodality management in a series of four cases and review of literature. Muller J Med Sci Res 2020;11:91-5

How to cite this URL:
Lohia N, Prashar M, Harish S, Singh S, Subramananiam A, Viswanath S, Ranjan R, Trivedi G. Primary anorectal melanoma: Multimodality management in a series of four cases and review of literature. Muller J Med Sci Res [serial online] 2020 [cited 2023 Mar 21];11:91-5. Available from: https://www.mjmsr.net/text.asp?2020/11/2/91/316695

Introduction

Anorectal malignant melanoma is a rare and highly lethal neoplasm constituting less than 1.3% of all melanomas and 16.5% of all mucosal melanomas.^[1] Common histologies of anorectal malignancies are adenocarcinoma or squamous cell carcinoma with melanoma, accounting for only 0.5%–4% of all colorectal and anal cancers.^[2],[3] Prognosis is dismal with a median survival of 24 months and a 5-year survival of 10%. The treatment of anorectal melanoma, unfortunately, is only moderately successful. Surgery remains the cornerstone of treatment. Different surgical modalities have been used in managing the disease with no clear evidence to favor one approach over another. As of date, there are no standard guidelines regarding adjuvant therapy due to lack of definitive randomized trials on optimal adjuvant regimen because of limited number of patients. Thus, because of limited number of such cases and retrospective design of all anorectal melanoma cases, no standard approach has been established to manage this rare and lethal neoplasm. In the present case study, we present four cases of melanoma of anorectum that were diagnosed and treated at our institution and discuss the clinical presentation, histological picture, and treatment offered in this rare entity. Informed consent was obtained from all patients in the study for use of their medical information without revealing their identities.

Case Reports

Patient 1

A 57-year-old male, a chronic tobacco chewer with no known comorbidities, presented to our hospital with complaints of constipation associated with hematochezia, tenesmus, and protrusion of a mass per rectum. Per rectal examination revealed an ulceroproliferative lesion in the rectum extending from anal verge proximally 5 cm into lower one-third of the rectum. He underwent colonoscopy, which showed a bluish friable growth starting from anal verge and reaching up to 8 cm proximally. Abdominopelvic contrast-enhanced computed tomography (CT) scan revealed a rectal mass with perirectal and bilateral iliac lymphadenopathy. Whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET) CT was negative for distant metastases and revealed FDG avid hypermetabolic anorectal mass with perirectal lymph nodes [Figure 1]. Histopathological examination of biopsy specimen displayed large cells with abundant eosinophilic and granular cytoplasm and prominent melanin pigmentation. There was marked cellular atypia with pleomorphic nuclei, large eosinophilic nucleoli, and frequent mitotic figures, suggestive of melanoma [Figure 2]. The patient underwent abdominoperineal resection (APR) with an end colostomy. The postoperative histopathological evaluation revealed dark brown polypoidal growth measuring 7.5 cm × 0.5 cm × 5 cm, reaching up to muscularis with proximal, distal, and circumferential resection margin free of tumor. Two out of 18 lymph nodes were positive for metastases. On immunohistochemistry (IHC), the tumor cells were immunoreactive for HMB-45 and S-100, thus confirming it to be a malignant melanoma. The postoperative period was uneventful. The patient was subjected to adjuvant chemotherapy with oral temozolomide (TMZ) 250 mg from day 1 to 5 and was planned for a minimum of six cycles. He could complete only first cycle of TMZ. Before scheduled second cycle of chemotherapy, he presented with breathlessness in very poor general condition. On evaluation, he was detected to have multiple lung metastases. In view of his poor general condition, he was kept on supportive terminal care and finally succumbed to his illness after about 1 month of the first cycle of TMZ and 3 months from the first presentation.

Figure 1: Positron emission tomography computed tomographic image showing hypermetabolic anorectal growth with pelvic lymph nodes

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Figure 2: Postoperative histopathological examination showing features typical of a melanoma

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Patient 2

A 53-year-old male with no known comorbidities presented with complaints of painful defecation associated with on and off hematochezia of 6 months' duration. On physical examination, there was a mass palpable in the rectum just proximal to the anal verge. Transabdominal ultrasonography of the anorectal zone displayed a growth involving anorectal ring and lower part of the rectum with enlarged left iliac group of lymph nodes. Histological findings were similar to previous case, suggestive of a melanoma. Abdominal contrast-enhanced computed tomography (CECT) scan showed a mass at distal rectum and anorectal junction measuring 8.2 cm × 6.5 cm × 6.5 cm, with extensive perilesional fat stranding and loss of fat planes with prostate anteriorly. Multiple left iliac lymph nodes were enlarged along with left para-aortic lymphadenopathy. Whole-body PET-CT corroborated with CT findings and was negative for distant metastases. The patient underwent APR with bilateral pelvic, inguinal, and para-aortic lymph node dissection along with permanent end colostomy. Histopathology revealed a dark brown growth measuring 9 cm × 6.5 cm × 4.5 cm reaching up to muscularis propria with proximal, distal, and circumferential resection margin free of tumor; all 24 lymph nodes dissected from around the growth were negative for metastases, while one out of ten pelvic lymph nodes and one out of 14 inguinal lymph nodes were positive for melanoma deposits. All five dissected para-aortic lymph nodes were negative for tumor cells. On IHC, the tumor cells were immunoreactive for HMB-45, vimentin, and S-100, thus confirming it to be malignant melanoma. The postoperative period was uneventful. The patient successfully completed all six cycles of adjuvant TMZ. However, 1 year after completion of treatment, he presented with left-sided hemiparesis and on evaluation was detected to have multiple brain metastases and lung metastases. He received palliative whole-brain radiotherapy to a dose of 30 Gy in 10 fractions. However, clinically, he continued to worsen and was deemed unfit for any further oncological intervention and was kept on supportive terminal care and finally succumbed to his illness around 18 months after the initial surgery.

Patient 3

A 66-year-old female with no known comorbidities presented with complaints of bleeding per rectum of 1-month duration associated with tenesmus. On digital rectal examination, an ulceroproliferative lesion starting just above anal verge and extending approximately 5 cm proximally on the right lateral wall of rectum from 6 O'clock to 10 O'clock position was palpable. The mass was not fixed to underlying structures. Video colonoscopy showed a bluish ulceroproliferative growth starting from anal verge and reaching up to 6 cm proximally. Abdominal CECT scan showed that an irregular heterogeneously enhancing wall thickening in the right posterolateral wall of the rectum with no infiltration beyond rectal wall was seen [Figure 3a] along with 13 mm × 11 mm presacral lymph node. Histopathological examination of punch biopsy was suggestive of melanoma with tumor cells immunopositive for HMB-45, S-100, and melan-A and immunonegative for CK. The patient underwent APR with bilateral pelvic lymph node dissection along with an end colostomy. Histopathology revealed a dark polypoid growth measuring 9 cm × 6 cm × 2 cm seen 3 cm from proximal and 1 cm from distal resection margin and was involving the bowel circumferentially. The tumor was invading wall of the rectum up to the serosa with proximal, distal, and circumferential resection margin grossly free of tumor. Grossly, the dissected lymph nodes were firm and blackish in color; three out of four lymph nodes dissected from around the growth were involved by tumor with black melanin-pigmented deposits with perinodal extension seen. Lymphovascular emboli were absent, and no perineural invasion was seen. On IHC, the tumor cells were immunopositive for HMB-45 and melan A with metastases of melanoma in the lymph node highlighted by HMB-45, thus confirming it to be malignant melanoma. The postoperative period was uneventful. The patient was subjected to adjuvant chemotherapy with oral TMZ 250 mg from day 1 to 5, along with injection cisplatin 75 mg/m² on day 1, and the cycle was repeated every 3 weekly. The patient successfully completed all six cycles of adjuvant doublet chemotherapy with TMZ and cisplatin. CECT of the chest, abdomen, and pelvis done at 3, 6, and 12 months postcompletion of chemotherapy revealed no evidence of disease [Figure 3b] and was negative for any locoregional and distant metastases. Currently, she is alive and is on regular follow-up with disease-free interval of almost 1 year.

Figure 3: Contrast-enhanced computed tomographic image (a) showing anorectal growth prior to treatment and (b) showing no evidence of growth posttreatment

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Patient 4

A 51-year-old male, with comorbidity of hypertension, presented with complaints of bleeding per rectum associated with tenesmus and protrusion of a mass per rectum. Physical examination revealed a mass in the rectum around 3 cm in size just proximal to the anal verge. The patient underwent colonoscopy, which showed a brownish friable growth starting from anal verge and reaching up to 3 cm proximally. Abdominopelvic CECT scan revealed heterogeneously enhancing asymmetric mural wall thickening with a maximum thickness of 9.8 mm seen in visualized anal canal for an approximate craniocaudal extent of 26 mm from the anal verge. The fat interface with adjacent structures was maintained. Few subcentimetric perirectal lymph nodes were seen along with multiple discrete and conglomerate peripherally enhancing lymph nodes with central hypodense areas, suggestive of necrosis seen along right common, external, and internal iliac vessels and right inguinal region. Further, few subcentimetric pre/para-aortic, aortocaval, and mesenteric lymph nodes were also seen. Histopathological examination of biopsy specimen was suggestive of melanoma. The patient underwent APR with bilateral pelvic, inguinal, and para-aortic lymph node dissection along with a permanent colostomy. The postoperative histopathology revealed tumor arranged in sheets with a high nuclear: cytoplasmic ratio, prominent nucleoli and occasional tumor cells with melanin pigment were seen, and the tumor was seen to infiltrating submucosa. The resected ends were free of tumor. Four out of 9 lymph nodes dissected from around the growth were positive for metastases, while one aortic bifurcation lymph node dissected was positive for melanoma deposits. On IHC, the tumor cells were immunoreactive for HMB-45 and S-100, thus confirming it to be a malignant melanoma. The postoperative period was uneventful. The patient was planned for adjuvant chemotherapy. However, he succumbed to cardiovascular accident, nononcological death around 5 weeks after surgery at his home town.

Discussion

Anorectal melanoma is very rare. Although uncommon, melanoma of the anal canal is the third most common site for primary melanoma, ranking behind cancer of the skin and eye, respectively. The first case of anorectal melanoma was described by Moore in 1857. It arises from melanocytic cells in the anal mucosa. It is often misdiagnosed in about two-third of patients as hemorrhoids or rectal polyp because of its rarity and histological variability and is also misdiagnosed at times as carcinoma, sarcoma, or lymphoma.^[4] It is usually a disease of women and typically presents in the fifth or sixth decade of life with rectal bleeding and altered bowel habits.^[5] Because of the rich vascular and lymphatic supply in anus, this tumor is highly aggressive, and by the time patient presents, it usually is already in an advanced stage. The tumor often metastasizes to both pelvic and inguinal lymph nodes.

Colonoscopy is essential not only for localizing and characterizing the lesion but also for obtaining a tissue biopsy. Endoscopic endorectal ultrasound may also be considered to evaluate tumor thickness and surrounding nodal status.^[6] The IHC markers for diagnosing melanoma are S-100, HMB-45, and vimentin. If biopsy shows a specimen to be suspicious for sarcoma, S-100 staining should be performed, and if it is positive, the tumor is most likely to be a melanoma. The most common sites for metastases from this tumor besides pelvic, inguinal, and para-aortic lymph nodes are liver, lung, skin and brain.^[7] Almost 60% of patients are metastatic by the time they are diagnosed.^[8] However, in all our four cases, the disease was limited to the rectum and anal canal with locoregional adenopathy (Stage II) at presentation.

Patients with anorectal melanoma have better survival if thickness is ≤ 2 mm rather than > 2 mm.^[9],[10] Goldman et al. found a correlation between overall survival and tumor size, showing greater overall survival for patients with tumors ≤ 2 cm.^[11] However, with delay in the diagnosis, majority of the patients with anorectal melanoma present to clinicians with tumor thickness >2 mm or a tumor size >2 cm and nodal involvement. Thus, Breslow depth alone is of little use in the staging. Hence, most authors advocated continued use of the clinical staging system developed for cutaneous melanoma based on locoregional and distant spread and is grouped as stage I (local disease), Stage II (local disease with regional lymph nodes), and Stage III (with distant metastasis).^[7],[12]

Differing opinions exist as to the ideal treatment of this disease, with no studies till date suggesting a definitive treatment protocol. However, surgery is the cornerstone of treatment though presently there is no consensus on the most favorable surgical approach.^[13] More aggressive surgical procedures such as APR have shown to improve local control and may enhance survival.^[14] Adjuvant chemotherapy or local radiation therapy also may provide further alleviation of symptoms and control tumor growth. No specific systemic chemotherapy regimen for metastatic anal melanoma is considered standard of care and is based on the drugs developed for advanced cutaneous melanoma. These are cisplatin, vinblastine, dacarbazine, interferon, and interleukin-2. An overall response rate of 44% and a complete response of 11% have been reported when different combinations of these drugs were used in 18 patients with metastatic anal melanoma.^[15] Dacarbazine or TMZ, in association with other agents, has demonstrated no advantage over single-agent chemotherapy in Phase III trials.^[16] However, even with aggressive therapy, a diagnosis of anorectal melanoma carries a poor prognosis.

There are no established standard regimens available for adjuvant therapy in anorectal melanoma because of the paucity of cases and scarcity of randomized trials. No trials have been published in the literature about the treatment of mucosal melanoma postsurgery. Hence, a prospective multicenter trial is required to arrive at an optimal primary and adjuvant treatment protocol in a disease that has a very poor outcome, despite aggressive surgery and chemotherapy.

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

Command Hospital (CC), Lucknow Cantt., supported the study.

Conflicts of interest

There are no conflicts of interest.

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