VOLUME
33
䡠
NUMBER
4
䡠
FEBRUARY
1
2015
JOURNAL OF CLINICAL ONCOLOGY
Wide Local Excision of Perianal Mucinous Adenocarcinoma Case Report A 67-year-old man was seen in surgical oncology clinic with a 6-month history of intermittent hematochezia and a new, palpable perineal mass (Fig 1). His previous surgical history was notable for two prior perineal abscesses. The first was 10 years prior and resolved after incision and drainage. The second was 3 years prior to this visit and did not respond to incision and drainage, requiring subsequent draining seton placement. The operative findings at that time revealed a complicated, intersphincteric fistula in ano. He was discharged from surgery clinic after an appropriate convalescence at 2 weeks. He had no interval follow-up for 3 years until he presented with hematochezia. He had no change in stool caliber or constitutional symptoms. His past medical history was notable for diabetes, cerebrovascular accident, and hyperlipidemia. There was no family history of colon cancer. Physical exam was remarkable for a 6 ⫻ 5-cm lesion in the left anterior perineum extending to the base of the scrotum, near the anal verge, and grossly separate from his anal canal. Laboratory findings included carcinoembryonic antigen of 2.0 ng/mL (normal, ⬍ 2.5 ng/mL). Punch biopsy of the perianal mass performed at initial presentation demonstrated adenomatous polypoid lesions with ulceration of the surrounding epidermis and dermis but no evidence of invasion of those polypoid lesions into dermal connective tissue. Colonoscopy revealed two diminutive hyperplastic polyps. No fistula or malignant intraluminal colorectal mass was found. Endoscopic ultrasound (EUS) was performed and did not show extension of this mass into the anal canal. Core biopsies guided by palpation were
D I A G N O S I S
I N
O N C O L O G Y
performed at the time of his colonoscopy and once again showed adenomatous tissue without evidence of invasion into adjacent dermal structures. Management options discussed included abdominoperineal resection (APR) or wide local excision. The patient was counseled that APR is generally offered as definitive therapy for perianal adenocarcinoma when it involves the anal canal. In his case, because there was no gross evidence of anal canal involvement, wide local excision could be considered for definitive diagnosis and as potential therapy. He strongly declined a permanent colostomy. He thus underwent successful and uncomplicated wide local excision of the perineal mass. Pathology demonstrated invasive adenocarcinoma, well-differentiated with endophytic (Figs 2A) and exophytic qualities (Fig 2B). Abundant mucin was noted in association with the sub-epithelial component. There were scattered
A
B
Fig 1. e16
© 2014 by American Society of Clinical Oncology
Fig 2. Journal of Clinical Oncology, Vol 33, No 4 (February 1), 2015: pp e16-e18
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
Diagnosis in Oncology
foci showing desmoplastic response with morphologic features consistent with progression from a tubulovillous adenoma. However, no colonic mucosa was present in association with the mass. It had features of invasion into dermal connective tissue and focally into skeletal muscle. The margins were negative with the closest being to the external sphincter surface at approximately 1 mm. Postoperatively, the patient underwent adjuvant treatment with capecitabine and concurrent external beam radiation therapy to 50.4 Gy, on the basis of multidisciplinary review and National Comprehensive Cancer Network rectal cancer protocols. Surveillance has included clinical evaluation every 6 months with perineal and inguinal nodal exams as well as anoscopy. Follow-up colonoscopy was performed and did not demonstrate any polyps. He has remained free of disease as of 28 months. Discussion Perianal mucinous adenocarcinoma can be classified as anal duct, ectopic perianal/ischiorectal, or associated with fistula in ano1 (Fig 3; WLE, wide local excision). The latter two subtypes have been grouped by the World Health Organization as extramucosal adenocarcinoma and currently are pathologically indistinguishable.2 Historically, these pathologic terms have been used interchangeably, resulting in a singular management strategy. Differentiating these subtypes allows for more individualized treatment options. Mucinous adenocarcinoma of the perineum was first described by Rosser3 in 1934. Recognizing that adenocarcinomas may originate from chronic fistulous disease, Rosser established three criteria for perianal adenocarcinoma associated with fistula in ano: that the fistula precede the carcinoma by at least 10 years, that the internal opening of the fistula is in the anal canal and outside the tumor itself, and that the only tumor present in the rectum or anal canal should be secondary to direct extension from the carcinoma in the fistula.1 Subsequent case reports have identified other types of perianal mucinous adenocarcinoma, such as those associated with anal ducts or ectopic anal glands.1,4,5 However, no formal diagnostic or classification criteria have been established. Although the exact incidence is not known, all types of perianal mucinous adenocarcinoma represent approximately 3% to 11% of perianal cancers.6-8 Risk factors include inflammatory bowel disease, prior fistulous disease, and diabetes.4,9,10 Patients may present with
Perianal Mucinous Adenocarcinomas Extramucosal Adenocarcinoma Anal duct
Perianal or ischiorectal
Associated with fistula in ano
Seeding from colorectal adenocarcinoma
APR
APR with WLE of perianal tissue Fig 3.
www.jco.org
Malignant degeneration
APR v WLE
anal pain, perianal mass, or rarely, with bleeding or obstruction.4,6 Persistent fistulous disease should raise suspicion of an underlying malignant process. Preoperative work-up consists of laboratory studies, colonoscopy, EUS, and/or magnetic resonance imaging. Carcinoembryonic antigen level can be elevated and may serve as a marker of metastasis. EUS delineates anatomy and extent of disease.6 A hyperintense T2 image on magnetic resonance imaging with enhanced solid component is suggestive of perianal mucinous adenocarcinoma.11 Core or punch biopsies may fail to reveal an invasive component of disease. Invasion can be demonstrated by findings in the subepithelial tissue of globules of mucin and/or invasion into dermal elements or skeletal muscle.12 Consideration can be made for incisional biopsy, but it may be limited by healing potential of ulcerated epidermis and dermis. In the absence of a definitive tissue specimen, the next step should be excision with the goal to achieve negative microscopic margins. Excisional biopsy with positive margins will mandate additional treatment, potentially an APR if the anal canal seems involved. Anal duct adenocarcinoma, originating from nonectopic tissue, is often an aggressive subtype warranting APR and adjuvant chemoradiotherapy with consideration for neoadjuvant therapy. This subtype represents approximately 10% to 20% of all anal carcinoma. Likewise, perianal adenocarcinoma associated with ectopic or remnant anal glands can have high local recurrence and warrants APR with wide local excision of perianal tissue to achieve negative margins. However, extramucosal adenocarcinoma originating from a fistula in ano represents a different pathologic subtype that may be amenable to wide excision only. It is critical to distinguish the origin of malignant cells in extramucosal perianal mucinous adenocarcinoma associated with a fistula as from either migration of an anal duct or rectal carcinoma or chronic stimulation and mucosal dysplastic changes in the fistulous tract.4,9,13-18 In the first subtype, malignant cells arise from colorectal mucosa via adenomatous changes and then migrate to seed a granulating fistula in ano.4,13-16 This pathologic subtype warrants aggressive surgical resection of the primary colorectal or anal tumor site and the satellite disease in the fistula in ano. The second source of malignant cells is dysplastic degeneration in recurrent or persistent fistulous disease. Chronic inflammation creates an immunologic privileged site as lymphatics are disrupted and surveillance is impaired.19 Mucosal irritation may cause either adenomatous dysplasia (eg, mucosal adenocarcinoma with cutaneous extension at the mucocutaneous junction of an ileostomy) or squamous dysplasia (eg, Marjolin’s ulcer).9,20-22 Distinguishing between these two origins of dysplastic cells is relevant and directly impacts management. The natural history and prognosis are not well known. Local spread does occur as the tumor invades into dermal structures then into adjacent organs.3 There are limited case reports of metastases to lymph nodes.6,23 However, because of disrupted lymphatics, there is no clear role for sentinel lymph node biopsy. While some reports claim an indolent course after diagnosis, others describe almost 100% mortality within one year.2 It is probable these disparate histories correlate more with histologic subtypes rather than the management approach. Regardless of the subtype, APR was historically considered the standard of care, particularly after early case series reported high likelihood of local recurrence.24 Sphincter-sparing wide local excision can be considered, particularly in the elderly, but long-term © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
e17
Ilbawi et al
outcomes are not known.25 In this case, when malignant transformation arose in the setting of chronically inflamed tissue and was grossly separate from the anal duct, definitive diagnosis and management was achieved with wide local excision to negative margins. This treatment approach can be further substantiated by the favorable prognosis associated with the similar management of ileostomy-associated mucinous adenocarcinoma.22 The roles for neoadjuvant and adjuvant therapy are also unclear. Generally, locoregional recurrence carries a poor prognosis in rectal cancer with some case series suggesting a similar outcome for perianal adenocarcinoma.6,26,27 Intestinal adenocarcinomas are sensitive to chemoradiotherapy, which has been validated in rectal cancer to reduce locoregional recurrence.27,28 Likewise, adjuvant chemoradiotherapy can be used in perianal adenocarcinoma associated with fistula in ano with the goal to reduce locoregional recurrence and improve survival; prospective data regarding this recommendation are needed. Perianal mucinous adenocarcinomas represent disparate clinical entities depending on pathophysiology and biology. Extramucosal mucinous adenocarcinoma associated with fistula in ano represents one specific subtype that may be amenable to wide local excision rather than APR. Diagnosis is made clinically and can be challenging because tissue samples may not reveal the presence or extent of invasion. If there is no evidence of anal canal involvement and the pathophysiology reflects chronic local inflammation, it is reasonable to proceed with wide local excision and a goal of negative margins. Adjuvant therapy can be used to reduce the likelihood of local recurrence. It is critical to state there are a limited number of case reports and this management decision should be made after counseling the patient and with multidisciplinary review. In the appropriate situation, the patient may be offered a sphincter-sparing procedure and achieve the goal of curative resection.
Andre´ M. Ilbawi and Vlad V. Simianu University of Washington School of Medicine, Seattle, WA
Michael Millie and Perry Soriano The Everett Clinic, Everett, WA
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Jensen SL, Shokouh-Amiri MH, Hagen K, et al: Adenocarcinoma of the anal ducts. A series of 21 cases. Dis Colon Rectum 31:268-272, 1988 2. World Health Organization: Tumours of the anal canal, in Hamilton SR, Aaltonen LA (eds): Pathology and Genetics of Tumours of the Digestive System. Lyon, France, International Agency for Research on Cancer, 2000, pp 146-155 3. Rosser C: The relation of fistula in ano to cancer of the anal canal. Trans Am Proct Soc 35:65-70, discussion 70-71, 1934 4. Sierra EM, Villanueva Saenz E, Martínez PH, et al: Mucinous adenocarcinoma associated with fistula in ano: Report of a case. Tech Coloproctol 10:51-53, 2006
5. Sato H, Maeda K, Maruta M, et al: Mucinous adenocarcinoma associated with chronic anal fistula reconstructed by gracilis myocutaneous flaps. Tech Coloproctol 10:249-252, 2006 6. Okada K, Shatari T, Sasaki T, et al: Is histopathological evidence really essential for making a surgical decision about mucinous carcinoma arising in a perianal fistula? Report of a case. Surg Today 38:555-558, 2008 7. Schaffzin DM, Stahl TJ, Smith LE: Perianal mucinous adenocarcinoma: Unusual case presentations and review of the literature. Am Surg 69:166-169, 2003 8. Abel ME, Chiu YS, Russell TR, et al: Adenocarcinoma of the anal glands: Results of a survey. Dis Colon Rectum 36:383-387, 1993 9. Smith R, Hicks D, Tomljanovich PI, et al: Adenocarcinoma arising from chronic perianal Crohn’s disease: Case report and review of the literature. Am Surg 74:59-61, 2008 10. Gaertner WB, Hagerman GF, Finne CO, et al: Fistula-associated anal adenocarcinoma: Good results with aggressive therapy. Dis Colon Rectum 51:1061-1067, 2008 11. Yang BL, Shao WJ, Sun GD, et al: Perianal mucinous adenocarcinoma arising from chronic anorectal fistulae: A review from single institution. Int J Colorectal Dis 24:1001-1006, 2009 12. Onerheim RM: A case of perianal mucinous adenocarcinoma arising in a fistula-in-ano: A clue to the early pathologic diagnosis. Am J Clin Pathol 89:809812, 1988 13. Katayama Y, Ihara K, Kimura M, et al: Carcinoma in anorectal fistula of rectal mucosal origin. Acta Pathol Jpn 34:649-654, 1984 14. Lee SH, Zucker M, Sato T: Primary adenocarcinoma of an anal gland with secondary perianal fistulas. Hum Pathol 12:1034-1037, 1981 15. Rollinson PD, Dundas SA: Adenocarcinoma of sigmoid colon seeding into pre-existing fistula-in-ano. Br J Surg 71:664-665, 1984 16. Wakatsuki K, Oeda Y, Isono T, et al: Adenocarcinoma of the rectosigmoid colon seeding into pre-existing anal fistula. Hepatogastroenterology 55:952-955, 2008 17. Dukes CE, Galvin C: Colloid carcinoma arising within fistulae in the anorectal region. Ann R Coll Surg Engl 18:246-261, 1956 18. Prioleau PG, Allen MS Jr, Roberts T: Perianal mucinous adenocarcinoma. Cancer 39:1295-1299, 1977 19. Getz SB Jr, Ough YD, Patterson RB, et al: Mucinous adenocarcinoma developing in chronic anal fistula: Report of two cases and review of the literature. Dis Colon Rectum 24:562-566, 1981 20. Anthony T, Simmang C, Lee EL, et al: Perianal mucinous adenocarcinoma. J Surg Oncol 64:218-221, 1997 21. Al-Niaimi F, Lyon CC: Primary adenocarcinoma in peristomal skin: A case study. Ostomy Wound Manage 56:45-47, 2010 22. Metzger PP, Slappy AL, Chua HK, et al: Adenocarcinoma developing at an ileostomy: Report of a case and review of the literature. Dis Colon Rectum 51:604-609, 2008 23. Bruce MB, Teague CA, Isbister WH: Perianal mucinous adenocarcinoma: A clue to its pathogenesis. Aust N Z J Surg 56:439-442, 1986 24. Nielsen OV, Koch F: Carcinomas of the anorectal region of extramucosal origin with special reference to the anal ducts. Acta Chir Scand 139:299-305, 1973 25. Yamaguchi T, Kagawa R, Sakata S, et al: Successful sphincter-sparing local excision for mucinous adenocarcinoma associated with chronic fistula in ano using preoperative MRI evaluation. Int Surg 93:220-225, 2008 26. Joon DL, Chao MW, Ngan SY, et al: Primary adenocarcinoma of the anus: A retrospective analysis. Int J Radiat Oncol Biol Phys 45:1199-1205, 1999 27. Habr-Gama A, Perez RO: Non-operative management of rectal cancer after neoadjuvant chemoradiation. Br J Surg 96:125-127, 2009 28. Kim E, Hwang JM, Garcia-Aguilar J: Local excision for rectal carcinoma. Clin Colorectal Cancer 7:376-385, 2008
DOI: 10.1200/JCO.2012.48.5722; published online ahead of print at www.jco.org on March 3, 2014
■ ■ ■
e18
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
33
䡠
NUMBER
4
䡠
FEBRUARY
1
2015
JOURNAL OF CLINICAL ONCOLOGY
Wide Local Excision of Perianal Mucinous Adenocarcinoma Case Report A 67-year-old man was seen in surgical oncology clinic with a 6-month history of intermittent hematochezia and a new, palpable perineal mass (Fig 1). His previous surgical history was notable for two prior perineal abscesses. The first was 10 years prior and resolved after incision and drainage. The second was 3 years prior to this visit and did not respond to incision and drainage, requiring subsequent draining seton placement. The operative findings at that time revealed a complicated, intersphincteric fistula in ano. He was discharged from surgery clinic after an appropriate convalescence at 2 weeks. He had no interval follow-up for 3 years until he presented with hematochezia. He had no change in stool caliber or constitutional symptoms. His past medical history was notable for diabetes, cerebrovascular accident, and hyperlipidemia. There was no family history of colon cancer. Physical exam was remarkable for a 6 ⫻ 5-cm lesion in the left anterior perineum extending to the base of the scrotum, near the anal verge, and grossly separate from his anal canal. Laboratory findings included carcinoembryonic antigen of 2.0 ng/mL (normal, ⬍ 2.5 ng/mL). Punch biopsy of the perianal mass performed at initial presentation demonstrated adenomatous polypoid lesions with ulceration of the surrounding epidermis and dermis but no evidence of invasion of those polypoid lesions into dermal connective tissue. Colonoscopy revealed two diminutive hyperplastic polyps. No fistula or malignant intraluminal colorectal mass was found. Endoscopic ultrasound (EUS) was performed and did not show extension of this mass into the anal canal. Core biopsies guided by palpation were
D I A G N O S I S
I N
O N C O L O G Y
performed at the time of his colonoscopy and once again showed adenomatous tissue without evidence of invasion into adjacent dermal structures. Management options discussed included abdominoperineal resection (APR) or wide local excision. The patient was counseled that APR is generally offered as definitive therapy for perianal adenocarcinoma when it involves the anal canal. In his case, because there was no gross evidence of anal canal involvement, wide local excision could be considered for definitive diagnosis and as potential therapy. He strongly declined a permanent colostomy. He thus underwent successful and uncomplicated wide local excision of the perineal mass. Pathology demonstrated invasive adenocarcinoma, well-differentiated with endophytic (Figs 2A) and exophytic qualities (Fig 2B). Abundant mucin was noted in association with the sub-epithelial component. There were scattered
A
B
Fig 1. e16
© 2014 by American Society of Clinical Oncology
Fig 2. Journal of Clinical Oncology, Vol 33, No 4 (February 1), 2015: pp e16-e18
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
Diagnosis in Oncology
foci showing desmoplastic response with morphologic features consistent with progression from a tubulovillous adenoma. However, no colonic mucosa was present in association with the mass. It had features of invasion into dermal connective tissue and focally into skeletal muscle. The margins were negative with the closest being to the external sphincter surface at approximately 1 mm. Postoperatively, the patient underwent adjuvant treatment with capecitabine and concurrent external beam radiation therapy to 50.4 Gy, on the basis of multidisciplinary review and National Comprehensive Cancer Network rectal cancer protocols. Surveillance has included clinical evaluation every 6 months with perineal and inguinal nodal exams as well as anoscopy. Follow-up colonoscopy was performed and did not demonstrate any polyps. He has remained free of disease as of 28 months. Discussion Perianal mucinous adenocarcinoma can be classified as anal duct, ectopic perianal/ischiorectal, or associated with fistula in ano1 (Fig 3; WLE, wide local excision). The latter two subtypes have been grouped by the World Health Organization as extramucosal adenocarcinoma and currently are pathologically indistinguishable.2 Historically, these pathologic terms have been used interchangeably, resulting in a singular management strategy. Differentiating these subtypes allows for more individualized treatment options. Mucinous adenocarcinoma of the perineum was first described by Rosser3 in 1934. Recognizing that adenocarcinomas may originate from chronic fistulous disease, Rosser established three criteria for perianal adenocarcinoma associated with fistula in ano: that the fistula precede the carcinoma by at least 10 years, that the internal opening of the fistula is in the anal canal and outside the tumor itself, and that the only tumor present in the rectum or anal canal should be secondary to direct extension from the carcinoma in the fistula.1 Subsequent case reports have identified other types of perianal mucinous adenocarcinoma, such as those associated with anal ducts or ectopic anal glands.1,4,5 However, no formal diagnostic or classification criteria have been established. Although the exact incidence is not known, all types of perianal mucinous adenocarcinoma represent approximately 3% to 11% of perianal cancers.6-8 Risk factors include inflammatory bowel disease, prior fistulous disease, and diabetes.4,9,10 Patients may present with
Perianal Mucinous Adenocarcinomas Extramucosal Adenocarcinoma Anal duct
Perianal or ischiorectal
Associated with fistula in ano
Seeding from colorectal adenocarcinoma
APR
APR with WLE of perianal tissue Fig 3.
www.jco.org
Malignant degeneration
APR v WLE
anal pain, perianal mass, or rarely, with bleeding or obstruction.4,6 Persistent fistulous disease should raise suspicion of an underlying malignant process. Preoperative work-up consists of laboratory studies, colonoscopy, EUS, and/or magnetic resonance imaging. Carcinoembryonic antigen level can be elevated and may serve as a marker of metastasis. EUS delineates anatomy and extent of disease.6 A hyperintense T2 image on magnetic resonance imaging with enhanced solid component is suggestive of perianal mucinous adenocarcinoma.11 Core or punch biopsies may fail to reveal an invasive component of disease. Invasion can be demonstrated by findings in the subepithelial tissue of globules of mucin and/or invasion into dermal elements or skeletal muscle.12 Consideration can be made for incisional biopsy, but it may be limited by healing potential of ulcerated epidermis and dermis. In the absence of a definitive tissue specimen, the next step should be excision with the goal to achieve negative microscopic margins. Excisional biopsy with positive margins will mandate additional treatment, potentially an APR if the anal canal seems involved. Anal duct adenocarcinoma, originating from nonectopic tissue, is often an aggressive subtype warranting APR and adjuvant chemoradiotherapy with consideration for neoadjuvant therapy. This subtype represents approximately 10% to 20% of all anal carcinoma. Likewise, perianal adenocarcinoma associated with ectopic or remnant anal glands can have high local recurrence and warrants APR with wide local excision of perianal tissue to achieve negative margins. However, extramucosal adenocarcinoma originating from a fistula in ano represents a different pathologic subtype that may be amenable to wide excision only. It is critical to distinguish the origin of malignant cells in extramucosal perianal mucinous adenocarcinoma associated with a fistula as from either migration of an anal duct or rectal carcinoma or chronic stimulation and mucosal dysplastic changes in the fistulous tract.4,9,13-18 In the first subtype, malignant cells arise from colorectal mucosa via adenomatous changes and then migrate to seed a granulating fistula in ano.4,13-16 This pathologic subtype warrants aggressive surgical resection of the primary colorectal or anal tumor site and the satellite disease in the fistula in ano. The second source of malignant cells is dysplastic degeneration in recurrent or persistent fistulous disease. Chronic inflammation creates an immunologic privileged site as lymphatics are disrupted and surveillance is impaired.19 Mucosal irritation may cause either adenomatous dysplasia (eg, mucosal adenocarcinoma with cutaneous extension at the mucocutaneous junction of an ileostomy) or squamous dysplasia (eg, Marjolin’s ulcer).9,20-22 Distinguishing between these two origins of dysplastic cells is relevant and directly impacts management. The natural history and prognosis are not well known. Local spread does occur as the tumor invades into dermal structures then into adjacent organs.3 There are limited case reports of metastases to lymph nodes.6,23 However, because of disrupted lymphatics, there is no clear role for sentinel lymph node biopsy. While some reports claim an indolent course after diagnosis, others describe almost 100% mortality within one year.2 It is probable these disparate histories correlate more with histologic subtypes rather than the management approach. Regardless of the subtype, APR was historically considered the standard of care, particularly after early case series reported high likelihood of local recurrence.24 Sphincter-sparing wide local excision can be considered, particularly in the elderly, but long-term © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
e17
Ilbawi et al
outcomes are not known.25 In this case, when malignant transformation arose in the setting of chronically inflamed tissue and was grossly separate from the anal duct, definitive diagnosis and management was achieved with wide local excision to negative margins. This treatment approach can be further substantiated by the favorable prognosis associated with the similar management of ileostomy-associated mucinous adenocarcinoma.22 The roles for neoadjuvant and adjuvant therapy are also unclear. Generally, locoregional recurrence carries a poor prognosis in rectal cancer with some case series suggesting a similar outcome for perianal adenocarcinoma.6,26,27 Intestinal adenocarcinomas are sensitive to chemoradiotherapy, which has been validated in rectal cancer to reduce locoregional recurrence.27,28 Likewise, adjuvant chemoradiotherapy can be used in perianal adenocarcinoma associated with fistula in ano with the goal to reduce locoregional recurrence and improve survival; prospective data regarding this recommendation are needed. Perianal mucinous adenocarcinomas represent disparate clinical entities depending on pathophysiology and biology. Extramucosal mucinous adenocarcinoma associated with fistula in ano represents one specific subtype that may be amenable to wide local excision rather than APR. Diagnosis is made clinically and can be challenging because tissue samples may not reveal the presence or extent of invasion. If there is no evidence of anal canal involvement and the pathophysiology reflects chronic local inflammation, it is reasonable to proceed with wide local excision and a goal of negative margins. Adjuvant therapy can be used to reduce the likelihood of local recurrence. It is critical to state there are a limited number of case reports and this management decision should be made after counseling the patient and with multidisciplinary review. In the appropriate situation, the patient may be offered a sphincter-sparing procedure and achieve the goal of curative resection.
Andre´ M. Ilbawi and Vlad V. Simianu University of Washington School of Medicine, Seattle, WA
Michael Millie and Perry Soriano The Everett Clinic, Everett, WA
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Jensen SL, Shokouh-Amiri MH, Hagen K, et al: Adenocarcinoma of the anal ducts. A series of 21 cases. Dis Colon Rectum 31:268-272, 1988 2. World Health Organization: Tumours of the anal canal, in Hamilton SR, Aaltonen LA (eds): Pathology and Genetics of Tumours of the Digestive System. Lyon, France, International Agency for Research on Cancer, 2000, pp 146-155 3. Rosser C: The relation of fistula in ano to cancer of the anal canal. Trans Am Proct Soc 35:65-70, discussion 70-71, 1934 4. Sierra EM, Villanueva Saenz E, Martínez PH, et al: Mucinous adenocarcinoma associated with fistula in ano: Report of a case. Tech Coloproctol 10:51-53, 2006
5. Sato H, Maeda K, Maruta M, et al: Mucinous adenocarcinoma associated with chronic anal fistula reconstructed by gracilis myocutaneous flaps. Tech Coloproctol 10:249-252, 2006 6. Okada K, Shatari T, Sasaki T, et al: Is histopathological evidence really essential for making a surgical decision about mucinous carcinoma arising in a perianal fistula? Report of a case. Surg Today 38:555-558, 2008 7. Schaffzin DM, Stahl TJ, Smith LE: Perianal mucinous adenocarcinoma: Unusual case presentations and review of the literature. Am Surg 69:166-169, 2003 8. Abel ME, Chiu YS, Russell TR, et al: Adenocarcinoma of the anal glands: Results of a survey. Dis Colon Rectum 36:383-387, 1993 9. Smith R, Hicks D, Tomljanovich PI, et al: Adenocarcinoma arising from chronic perianal Crohn’s disease: Case report and review of the literature. Am Surg 74:59-61, 2008 10. Gaertner WB, Hagerman GF, Finne CO, et al: Fistula-associated anal adenocarcinoma: Good results with aggressive therapy. Dis Colon Rectum 51:1061-1067, 2008 11. Yang BL, Shao WJ, Sun GD, et al: Perianal mucinous adenocarcinoma arising from chronic anorectal fistulae: A review from single institution. Int J Colorectal Dis 24:1001-1006, 2009 12. Onerheim RM: A case of perianal mucinous adenocarcinoma arising in a fistula-in-ano: A clue to the early pathologic diagnosis. Am J Clin Pathol 89:809812, 1988 13. Katayama Y, Ihara K, Kimura M, et al: Carcinoma in anorectal fistula of rectal mucosal origin. Acta Pathol Jpn 34:649-654, 1984 14. Lee SH, Zucker M, Sato T: Primary adenocarcinoma of an anal gland with secondary perianal fistulas. Hum Pathol 12:1034-1037, 1981 15. Rollinson PD, Dundas SA: Adenocarcinoma of sigmoid colon seeding into pre-existing fistula-in-ano. Br J Surg 71:664-665, 1984 16. Wakatsuki K, Oeda Y, Isono T, et al: Adenocarcinoma of the rectosigmoid colon seeding into pre-existing anal fistula. Hepatogastroenterology 55:952-955, 2008 17. Dukes CE, Galvin C: Colloid carcinoma arising within fistulae in the anorectal region. Ann R Coll Surg Engl 18:246-261, 1956 18. Prioleau PG, Allen MS Jr, Roberts T: Perianal mucinous adenocarcinoma. Cancer 39:1295-1299, 1977 19. Getz SB Jr, Ough YD, Patterson RB, et al: Mucinous adenocarcinoma developing in chronic anal fistula: Report of two cases and review of the literature. Dis Colon Rectum 24:562-566, 1981 20. Anthony T, Simmang C, Lee EL, et al: Perianal mucinous adenocarcinoma. J Surg Oncol 64:218-221, 1997 21. Al-Niaimi F, Lyon CC: Primary adenocarcinoma in peristomal skin: A case study. Ostomy Wound Manage 56:45-47, 2010 22. Metzger PP, Slappy AL, Chua HK, et al: Adenocarcinoma developing at an ileostomy: Report of a case and review of the literature. Dis Colon Rectum 51:604-609, 2008 23. Bruce MB, Teague CA, Isbister WH: Perianal mucinous adenocarcinoma: A clue to its pathogenesis. Aust N Z J Surg 56:439-442, 1986 24. Nielsen OV, Koch F: Carcinomas of the anorectal region of extramucosal origin with special reference to the anal ducts. Acta Chir Scand 139:299-305, 1973 25. Yamaguchi T, Kagawa R, Sakata S, et al: Successful sphincter-sparing local excision for mucinous adenocarcinoma associated with chronic fistula in ano using preoperative MRI evaluation. Int Surg 93:220-225, 2008 26. Joon DL, Chao MW, Ngan SY, et al: Primary adenocarcinoma of the anus: A retrospective analysis. Int J Radiat Oncol Biol Phys 45:1199-1205, 1999 27. Habr-Gama A, Perez RO: Non-operative management of rectal cancer after neoadjuvant chemoradiation. Br J Surg 96:125-127, 2009 28. Kim E, Hwang JM, Garcia-Aguilar J: Local excision for rectal carcinoma. Clin Colorectal Cancer 7:376-385, 2008
DOI: 10.1200/JCO.2012.48.5722; published online ahead of print at www.jco.org on March 3, 2014
■ ■ ■
e18
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Universiteitsbibliotheek Utrecht on March 13, 2015 from Copyright © 2015 American Society of Clinical Oncology. All rights reserved. 131.211.208.19
