J Pathol Transl Med.  2016 May;50(3):231-237. 10.4132/jptm.2015.08.08.

Rare Case of Anal Canal Signet Ring Cell Carcinoma Associated with Perianal and Vulvar Pagetoid Spread

• Kim NR
• Cho HY
• Baek JH
• Jeong J
• Ha SY
• Seok JY
• Park SW
• Sym SJ
• Lee KC
• Chung DH

• KMID: 2164601
• DOI: http://doi.org/10.4132/jptm.2015.08.08

Abstract

A 61-year-old woman was referred to surgery for incidentally found colonic polyps during a health examination. Physical examination revealed widespread eczematous skin lesion without pruritus in the perianal and vulvar area. Abdominopelvic computed tomography showed an approximately 4-cm-sized, soft tissue lesion in the right perianal area. Inguinal lymph node dissection and Mils' operation extended to perianal and perivulvar skin was performed. Histologically, the anal canal lesion was composed of mucin-containing signet ring cells, which were similar to those found in Pagetoid skin lesions. It was diagnosed as an anal canal signet ring cell carcinoma (SRCC) with perianal and vulvar Pagetoid spread and bilateral inguinal lymph node metastasis. Anal canal SRCC is rare, and the current case is the third reported case in the English literature. Seven additional cases were retrieved from the world literature. Here, we describe this rare case of anal canal SRCC with perianal Pagetoid spread and provide a literature review.

Keyword

Carcinoma, signet ring cell; Anal canal; Paget disease, extramammary

MeSH Terms

Anal Canal*
Carcinoma, Signet Ring Cell*
Colonic Polyps
Female
Humans
Lymph Node Excision
Lymph Nodes
Middle Aged
Neoplasm Metastasis
Paget Disease, Extramammary
Physical Examination
Pruritus
Skin

Figure

• 

  Fig. 1. Radiologic findings. (A) Abdominal computed tomography reveals a well-enhancing lesion (arrow) at the right perianal portion. (B) Enlarged bilateral inguinal lymph nodes (arrows) are found.

• 

  Fig. 2. Gross pictures. (A) Perianal and vulvar skin shows elevated erythematous changes. (B) Extended Miles’ operation specimen consists of distal rectal segment and excision of perianal region and vulva. (C) Cross-section of the resected specimen shows a firm anal canal mass infiltrating to the perianal skin and levator ani muscle.

• 

  Fig. 3. (A) A transmural, yellowish gray firm mass is composed of singly scattered signet ring cells and some extracellular mucin. Note the surface mucosal erosion. (B) The majority of the mass is infiltrated by signet ring carcinoma cells, and poorly differentiated mucinous glands are floating in the mucin pool. Inset indicates high magnification of signet ring cells showing intracytoplasmic mucin compressing the hyperchromatic nuclei to the periphery. (C) The transformation zone of the anal canal shows infiltration of multifocal signet ring cell carcinoma (white arrows) and a focus of atypical gland beneath the mucosa (black arrow). Inset shows adenocarcinoma in situ with a gland having enlarged hyperchromatic nuclei with coarse chromatin and increased nuclear/cytoplasmic ratio. (D) Large Paget cells showing clear cytoplasm with eccentric hyperchromic nuclei are located along the basal layer of the squamous epithelium. Inset indicates Paget cells in the epidermis.

Reference

1. Inamura K, Yamauchi M, Nishihara R, et al. Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma. Ann Surg Oncol. 2015; 22:1226–35.

2. Chu PG, Weiss LM. Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol. 2004; 121:884–92.

3. Uchigasaki S, Ochiai T, Miyakawa K, Suzuki H, Morishima T. Circumanal Paget’s disease which was complicated by anus cancers after 15 years. Skin Cancer. 1992; 7:254–8.

4. Ioannidis O, Papaemmanouil S, Paraskevas G, et al. Primary signet ring cell anal adenocarcinoma. J Gastrointest Cancer. 2012; 43 Suppl 1:168–70.

5. Terada T. Primary pure signet-ring cell carcinoma of the anus: a case report with immunohistochemical study. Endoscopy. 2014; 46 Suppl 1 UCTN:E347.

6. Lopes Filho LL, Lopes IM, Lopes LR, Enokihara MM, Michalany AO, Matsunaga N. Mammary and extramammary Paget’s disease. An Bras Dermatol. 2015; 90:225–31.

7. Morihisa A, Nobutoh T, Kohda M, Ueki H. An autopsy case of anal canal cancer showing Paget’s disease as the first sign. Jpn J Clin Dermatol. 1999; 53:758–60.

8. Nagano Y, Nanko M, Nagahori Y. Rectal signet ring cell carcinoma associated with perianal Paget’s disease: report of a case. J Jpn Surg Assoc. 1999; 60:473–6.

9. Naganuma H, Ottomo S, Takaya K, Sakai N, Tamahashi N, Takahashi T. An autopsy case of anal canal cancer (signet ring cell carcinoma) accompanied with perianal Pagetoid spread. Jpn J Diagn Pathol. 2004; 21:129–32.

10. Nishimura H, Kaneko T, Mizuki D, et al. A case of anal canal cancer presenting a pagetoid phenomenon in the perianal lesion. Jpn J Clin Dermatol. 2004; 58:674–7.

11. Yoshitani S, Hosokawa K, Yokoi M, et al. A case of anal canal carcinoma with systemic lymph node metastases successfully treated by bevacizumab+mFOLFOX6 therapy. Gan To Kagaku Ryoho. 2009; 36:2229–31.

12. Ikezawa F, Miura K, Shibata C, et al. Pagetoid spread with anal canal poorly differentiated adenocarcinoma: a case report. Jpn J Gastroenterol Surg. 2010; 43:678–84.

13. Moritani Y, Tomioka N, Izumi A, Takiue T, Kobayashi N, Shirakawa Y. A case of anal gland carcinoma accompanied by Pagetoid spread. Nippon Daicho Komonbyo Gakkai Zasshi. 2009; 62:121–6.

14. Welton ML, Lambert R, Bosman FT. Tumours of the anal canal. In : Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. 4th ed. Lyon: IARC Press;2010. p. 183–93.

15. Grelck KW, Nowak MA, Doval M. Signet ring cell perianal paget disease: loss of MUC2 expression and loss of signet ring cell morphology associated with invasive disease. Am J Dermatopathol. 2011; 33:616–20.

16. Ohnishi T, Watanabe S. The use of cytokeratins 7 and 20 in the diagnosis of primary and secondary extramammary Paget’s disease. Br J Dermatol. 2000; 142:243–7.

17. Ogino S, Nosho K, Kirkner GJ, et al. CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. Gut. 2009; 58:90–6.

18. Kang H, O’Connell JB, Maggard MA, Sack J, Ko CY. A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum. 2005; 48:1161–8.

19. Shridhar R, Shibata D, Chan E, Thomas CR. Anal cancer: current standards in care and recent changes in practice. CA Cancer J Clin. 2015; 65:139–62.