Primary Mucinous Cystic Neoplasm of the Retroperitoneum - a Report of Three Cases

대한병리학회지: 제 37 권제3 호 2003 The Korean Journal of Pathology. 2003; 37: 204-9

Primary Mucinous Cystic Neoplasm of the Retroperitoneum - A Report of Three Cases -

Dong Eun Song∙Mi-Jung Kim Primary mucinous cystic neoplasms of the retroperitoneum in women are rare and show his- Shin Kwang Khang∙Eunsil Yu tologic features similar to their ovarian or pancreatic counterparts. We present three cases of Kyung-Ja Cho primary retroperitoneal mucinous neoplasms of variable malignant potentials including a cystadenocarcinoma in a 50-year-old woman, a cystic neoplasm of borderline malignancy in a 31- Department of Pathology, University of year-old woman, and a cystadenoma in a 67-year-old woman. All cases showed histologic Ulsan College of Medicine, Asan features similar to mucinous tumors of the ovary. Immunohistochemical study demonstrated Medical Center, Seoul, Korea positivity for calretinin in case 3. The histogenesis of these neoplasms can be assumed most likely to be mucinous metaplasia of the mesothelium or undetected heterotopic pancreatic tissue. Received : August 22, 2002 Accepted : April 22, 2003 Appropriate management is thought to be the same as for analogous ovarian neoplasms. Corresponding Author Kyung-Ja Cho, M.D. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, Korea Tel: 02-3010-4545 Fax: 02-472-7898 E-mail: [email protected] Key Words : Retroperitoneum, Primary Mucinous Cystic Naeoplasm

The primary mucinous cystic neoplasm of the retroperitoneum was discovered in the retroperitoneum below the left kidney. On is rare. Only 29 cases have been reported in literature to date, in- abdominal and pelvic computed tomography (CT) with contrast, cluding 2 cases in domestic literature.1-20 They encompass benign, this tumor was found to be located around the pancreatic tail por- borderline and malignant varieties and show a histologic simi- tion and had lobulating contour (Fig. 1). The laboratory data sh- larity to the ovarian mucinous tumors. Although several theories owed a slight elevation of CA-125 (41 UI/mL) and marked ele- have been proposed, the histogenesis of this neoplasm is still uncer- vation of CA 19-9 (1,510 UI/mL). The levels of CEA (4.7 ng/mL) tain. Mucinous or coelomic metaplasia of the retroperitoneal me- and -fetoprotein (1.4 ng/mL) were within normal limits. The sothelium, proposed by Lauchlan,5,7 has gained wide acceptance. cystic mass was located in the mesentery, and no anatomical con- We report three cases of primary retroperitoneal mucinous cys- nections with the pancreas including the tail portion, ovaries, or tic neoplasm ranging the spectrum from benign to malignant small bowel were found. It was initially intact and was removed histologic features, and discuss the histogenesis and appropriate by laparoscopic procedure after the aspiration of the cyst content treatment for these rare neoplasms. to reduce the tumor volume. Grossly, the tumor was a lobulated multiseptate cystic mass (10×9×5 cm and 238 gm), filled with white to yellow thick CASE 1 mucoid material (Fig. 2). The outer surface was grayish tan and glistening, and showed a fibrous adhesion site. The inner surface A 50-year-old woman was admitted to our hospital. She com- was pinkish tan, glistening, and irregular with frond-like areas plained of a palpable abdominal mass in the left upper quadrant and a few solid mural nodules. that she’d had for one month. The previous routine gynecologi- Microscopically, the tumor was composed of irregular multi- cal examination had revealed no abnormalities. On ultrasonog- locular cysts lined by columnar cells with mucinous or eosinophilic raphy, a huge multiseptate cystic mass with a few mural nodules cytoplasm, which were flat or piled up with micropapillary pro-

204 Primary Mucinous Cystic Neoplasm of the Retroperitoneum 205

Fig. 1. Abdominal computed tomography of Case 1 shows a lob- Fig. 2. Gross photograph of Case 1 shows a multiseptate cystic ulated cystic tumor in the left side of the retroperitoneum. mass (10×9×5 cm) with pinkish tan, glistening, and irregular inner surface.

trusions showing benign to borderline appearances (Fig. 3A). The the previous operation site, and the remaining solid organs showed adenocarcinoma components were well differentiated with a crib- no metastasis. The patient received chemotherapy using Taxol, riform pattern (Fig. 3B). The stroma consisted of hypocellular but expired ten months after the operation. fibrous or cellular ovarian stroma-like tissue. There were a few anaplastic mural nodules consisting of spindle or multinucleated cells with malignant features, including marked cellular pleomor- CASE 2 phism and high mitotic activity, mixed with mucinous glandular components (Fig. 3C). Some tumor cells lining the cyst showed A 31-year-old woman was admitted to our hospital. She com- strong positivity for Alcian-blue and periodic acid schiff (PAS) plained of abdominal distension in the right lower quadrant that stainings, but negativity for calretinin by immunohistochemi- she’d had for one year. On abdominal and pelvic computed tomog- cal staining. The only mucinous glandular components in the raphy with contrast, a multiseptate cystic mass with calcifications anaplastic mural nodules showed strong positivity for cytoker- was detected in the right retroperitoneum. The laboratory data atin by immunohistochemical staining (Fig. 3D). This tumor was for CA 72-4 in serum was within the normal limit (1.9 /mL). diagnosed to be a primary retroperitoneal mucinous cystadeno- At excision, using a mid-line incision, a well-encapsulated, soft carcinoma. and glistening cystic mass was found in the right retroperitoneal After the laparoscopic operation, the level of CA 19-9 decreased space behind the ascending colon. The mass was easily separat- to 26.5 IU/mL at the two months follow-up, but re-increased to ed from the ascending colon without adhesion. Other solid organs 41.9 IU/mL at the four months follow-up. It increased up to 549 including both ovaries were intact. Incidental appendectomy was IU/mL at the ten months follow-up. The follow-up CT at post- also performed. operative six and eight months revealed neither local recurrence Grossly, the tumor was a smooth-surfaced, multilocular cyst nor distant metastasis despite increased levels of CA 19-9. But, (21×16×10 cm and 210 gm), filled with grayish green tur- it revealed thickening of the walls of the cecum and ascending bid fluid. The inner surface was grayish tan and glistening, and colon with pericolic fat infiltration: both paracolic gutters had showed calcified septa without any solid nodules. thickened and there was a presence of multiple mesenteric lym- Microscopically, the cyst was mostly lined by single layered phadenopathy at the ten months follow-up, which were sugges- low cuboidal or tall columnar cells with mucinous or eosinophilic tive of peritoneal seeding. No recurred mass was identified around cytoplasm (Fig. 4A). In addition, small papillae or glands com- 206 Dong Eun Song∙Mi-Jung Kim∙Shin Kwang Khang, et al.

A B

Fig. 3. (A) The multilocular cystic wall is lined by mucinous columnar cells, which are flat or piled up with micropapillary protrusions. (B) Well differentiated adenocarcinoma components are present in the cystic wall. (C) The mural nodule consists of anaplastic spindle or multinucleated cells and is mixed with mucinous glandular components. (D) The mucinous glandular components in the mural C D nodule show positive immunoreactivity for cytokeratin. posed of stratified hyperchromatic nuclei were occasionally ob- CASE 3 served (Fig. 4B). The stroma consisted of cellular ovarian stroma- like tissue or collagenous tissue with multifocal calcifications. A 67-year-old woman was admitted to our hospital. She com- Obvious malignant features or stromal invasion were not present. plained of abdominal discomfort in the right upper quadrant that Immunohistochemistry showed a negative reaction for calretinin she’s had for several months. On abdominal and pelvic comput- in the nucleus and cytoplasm of low cuboidal cells. This tumor ed tomography with contrast, a 5.1 cm sized cystic mass with was diagnosed to be a primary retroperitoneal mucinous cystic homogeneous low attenuation was detected in the posterior lat- neoplasm of borderline malignancy. The appendix was normal. eral side of the ascending colon. There was no lymphadenopa- The post-operative gynecological examination revealed no abnor- thy and the liver showed a tiny nodule in segment VIII, which malities. was too small to characterize. The laboratory data for CEA in serum was within the normal limit (1.9 ng/mL). At laparotomy, Primary Mucinous Cystic Neoplasm of the Retroperitoneum 207

A B

Fig. 4. (A) The cystic wall is lined by low cuboidal or tall columnar cells. (B) Borderline malignancy foci show moderate nuclear atypia, stratification, and ovarian-like stroma. low cuboidal or tall columnar cells with mucinous cytoplasm (Fig. 5A). The tumor cells showed no evidence of stratification, pleomorphism, or papillary arrangement. The stroma consisted of hypocellular collagenous tissue with multifocal calcifications. PAS and alcian-blue stainings showed a strong positive reaction in the cytoplasm of tall columnar cells. Immunohistochemistry showed positive reaction for calretinin in the nucleus and cyto-

A plasm of some low cuboidal cells (Fig. 5B). This tumor was diagnosed to be a primary retroperitoneal mucinous cystadenoma. The patient was lost to follow-up 3 months after the operation.

DISCUSSION

Primary retroperitoneal mucinous cystic neoplasms in women are rare. There have been 29 cases reported to date.1-20 This neo- B plasm covers the spectrum from benign to malignant, and a case Fig. 5. (A) The cystic wall is lined by low cuboidal or tall columnar with distant metastasis was reported by Banerjee and Gough.1 cells and hypocellular collagenous stroma. (B) The lining low cu- The origin of this rare neoplasm has been a matter of debate boidal cells show positive immunoreactivity for calretinin. because of its location and its histologic features being similar to a well-defined, soft and round cystic mass was found in the right that of its ovarian counterpart. The precise histogenesis of this retroperitoneal space behind the paracolic gutter. neoplasm has not been defined; however, several hypotheses are Grossly, the tumor was a smooth-surfaced unilocular cyst (7.5 proposed in literature. ×5×5 cm and 170 gm), filled with slight yellow serous fluid. Frank5 reported a papillary cystadenoma in a retroperitoneal The inner surface was whitish tan, smooth and glistening with- supernumerary ovary as early as 1909. Wharton7 documented the out any solid portions or papillary excrescences. presence of accessory and supernumerary ovaries at autopsy and Microscopically, the cyst was lined by a single layer of flattened postulated the possibility of heterotopic ovarian tissue as an ori- 208 Dong Eun Song∙Mi-Jung Kim∙Shin Kwang Khang, et al. gin. Meyer7 considered these neoplasms to represent the mono- ruptures or invasive foci are microscopically noted, adjuvant ther- dermal variant of retroperitoneal teratomas. Hansmann and Budd7 apy with cis-platinum-based chemotherapy or radiation, or a com- proposed the development to be from the embryonal urogenital bination of both, may be required. Re-exploration laparotomy remnants and the possibility of a mesonephric origin for the neo- with complete surgical staging for the mucinous cystadenocar- plasm. Abascal7 suggested an enterogenous origin from intesti- cinoma, as in the ovarian counterpart, is controversial for its ben- nal duplication. Recently, Lauchlan5,7 postulated that the peri- efit; but it is recommended because of rare local recurrences and toneal mesothelium retains the potential for mullerian. . differen- distant metastases.1 tiation, with the possibility that the development of the tumor shows the same histologic features as ovarian tumors. During embryogenesis, the coelomic epithelium is multipotential and REFERENCES gives rise to the peritoneum as well as the germinal epithelium of the ovary. As in the ovary, this epithelium may undergo muci- 1. Banerjee R, Gough J. Cystic mucinous tumors of the mesentery and nous metaplasia with cyst formation and gain the potential for retroperitoneum; report of three cases. Histopathology 1988; 12: 527- malignant transformation. In a the recent study by Tenti et al.8, 32. two cases of primary retroperitoneal mucinous cystadenocarcino- 2. Uematsu T, Kitamura H, Iwase M, et al. Ruptured retroperitoneal mas revealed a similarity to their ovarian counterpart by immuno- mucinous cystadenocarcinoma with synchronous gastric carcinoma histochemical stainings for gastroenteropancreatic antigens and and a long postoperative survival: case report. J Surg Oncol 2000; 73: DNA analysis for point mutation of K-ras oncogene. 26-30. We could not find the heterotopic ovarian tissue, teratoid com- 3. Papadogiannakis N, Gad A, Ehliar B. Primary retroperitoneal muci- ponent, or digestive tract remnants in any of our cases. The posi- nous tumor of low malignant potential: histogenetic aspects and re- tive immunoreactivity for calretinin of some low cuboidal cells view of the literature. APMIS 1997; 105: 483-6. in case 3 demonstrates its being of mesothelial origin and sug- 4. Lee IW, Ching KC, Pang M, Ho TH. Two cases of primary retroperi- gests that this neoplasm may have arisen from mesothelial cells toneal mucinous cystadenocarcinoma. Gynecol Oncol 1996; 63: 145- through subsequent mucinous metaplasia. Thus, mucinous meta- 50. plasia of the retroperitoneal mesothelium, by Lauchlan, is consid- 5. Tenti P, Carnevali L, Tateo S, Durola R. Primary mucinous cystoade- ered to be the most possible histogenesis in case 3. nocarcinoma of the retroperitoneum: two cases. Gynecol Oncol 1994; The histologic features such as ovarian-like stroma and anaplas- 55: 308-12. tic mural nodules in case 1 are reminiscent of both pancreatic and 6. Carabias E, Garcia Munoz H, Dihmes FP, et al. Primary mucinous ovarian mucinous cystadenocarcinomas. The tumor in case 1 sh- cystadenocarcinoma of the retroperitoneum. Report of a case and lit- owed a strong correlation with the level of CA 19-9 in the initial erature review. Virchows Arch 1995; 426: 641-5. diagnosis, treatment, and follow-up. Thus, we could not entire- 7. Pearl ML, Valea F, Chumas J, Chalas E. Primary retroperitoneal muci- ly exclude the possibility that the undetected heterotopic pancreas nous cystadenocarcinoma of low malignant potential: a case report might be the origin of the tumor in case 1, but no pancreatic tis- and literature review. Gynecol Oncol 1996; 61: 150-2. sue was detected in the specimen of case 1. The tumor showed 8. Tenti P, Romagnoli S, Pellegata NS, et al. Primary retroperitoneal mu- no anatomical connection with the pancreas, ovaries, or the adja- cinous cystoadenocarcinomas: an immunohistochemical and molec- cent gastrointestinal tract at the operation field; and the tumor ular study. Virchows Arch 1994; 424: 53-7. markers, except for CA 19-9, did not significantly increase. There- 9. Gotoh K, Konaga E, Arata A, Takeuchi H, Mano S. A case of prima- fore, we concluded the tumor of case 1 to be of primary retroperi- ry retroperitoneal mucinous cystadenocarcinoma. Acta Med Okaya- toneal origin, excluding the possibility of a distant metastasis. ma 1992; 46: 49-52. The treatment for primary retroperitoneal mucinous neoplasms 10. Jorgensen LJ, Vibits H. Primary retroperitoneal mucinous cystade- is considered to be similar to their ovarian counterparts. It is defi- nocarcinoma. A case report and review of the literature. APMIS 1991; nitely important to remove these tumors without rupture, and 99: 1055-7. laparoscopic removal should be avoided if the histology of the 11. Seki H, Shiina M, Nishihara M, et al. Primary retroperitoneal muci- tumor is unclear. The peritoneal seeding in the patient of case 1 nous cystadenocarcinoma: report of a case. Radiat Med 1990; 8: 164-7. might be a result of laparoscopic removal including the aspira- 12. Nelson H, Benjamin B, Alberty R. Primary retroperitoneal mucinous tion procedure to reduce the tumor volume. If the malignant cyst cystadenocarcinoma. Cancer 1988; 61: 2117-21. Primary Mucinous Cystic Neoplasm of the Retroperitoneum 209

13. Balat O, Aydin A, Sirikci A, Kutlar I, Aksoy F. Huge primary muci- 17. Rothacker D, Knolle J, Stiller D, Borchard F. Primary retroperitoneal nous cystadenoma of the retroperitoneum mimicking a left ovarian mucinous cystadenomas with gastric epithelial differentiation. Pathol tumor. Eur J Gynaecol Oncol 2001; 22: 454-5. Res Pract 1993; 189: 1195-204. 14. Subramony C, Habibpour S, Hashimoto LA. Retroperitoneal muci- 18. Park SW, Kim JW, Kim SK, Kim YT, Yoon HJ, Kim JY. A case of pri- nous cystadenoma. Arch Pathol Lab Med 2001; 125: 691-4. mary retroperitoneal mucinous cystadenocarcinoma. Korean J Obstet 15. Chen JS, Lee WJ, Chang YJ, Wu MZ, Chiu KM. Laparoscopic resec- Gynecol 1997; 40: 914-8. tion of a primary retroperitoneal mucinous cystadenoma: report of 19. Kim EK, Hong SR, Kim HS, Ko YH, Lee JD. Retroperitoneal mucinous a case. Surg Today 1998; 28: 343-5. tumor. Repor of two cases. Korean J Pathol 1992; 26: 632-4. 16. Bortolozzi G, Grasso A, Zasso B. Mucinous cystadenoma of the re- 20. Park UD, Han KC, Chang HK, Huh MH. A primary mucinous cys- troperitoneum. A case report and review. Eur J Gynaecol Oncol 1995; tadenocarcinoma of the retroperitoneum. Gynecol Oncol 1991; 42: 16: 65-8. 64-7.