Pseudomyxoma peritonei

* Primary cystadenocarcinoma that arises in the broad ligament is extremely rare, especially when it is mucinous. We report the case of a 59-year-old woman with a cystic mass of the right broad ligament who underwent a complete excision of the mass (7 × 7 × 3 cm) with hysterectomy, right salpingo-oophorectomy, omentectomy, appendicectomy, and peritoneal biopsies. Pathologic examination showed a low-grade cystadenocarcinoma with a mucinous component limited to the broad ligament. Despite the chemotherapy (cisplatinum and cyclophosphamide) performed, early tumor recurrence occurred after approximately 6 months. Our observation revealed an abundant mucin production with pools of mucin similar to those of pseudomyxoma peritonei and an inflammatory infiltrate with prominent lipid phagocytosis, Immunohistochemical analysis demonstrated a strong and diffuse positivity for both cytokeratin 7 and epithelial membrane antigen. A less extensive staining with carcinoembryonic antigen and a focal unequivocal positivity with cytokeratin 20, particularly in mucin-secreting cells, were also observed, this finding could indicate a metaplastic process toward colonie phenotype similar to primary ovarian tumors.

(Arch Pathol Lab Med. 2005;129:244-246)

Although the secondary involvement of the broad ligament by malignant tumors is common, primary tumors in this site are rare,1 especially primary malignant tumors, either epithelial or nonepithelial.1-6 In fact, nearly all reported cases are benign tumors and cysts of mullerian (paramesonephric) or wolffian (mesonephric) duct origin. We report a case of a cystadenocarcinoma with a mucinous component in the broad ligament of a 59-year-old woman.

REPORT OF A CASE

A 59-year-old, para 6, gravida 4, postmenopausal woman with an uneventful gynecologic history was referred to our institution with a diagnosis of a right adnexal tumor revealed by a right leg thrombosis. The etiologic workup, which was composed of an abdominal ultrasonographic examination and a computed tomography study, showed a cystic mass posterior to the uterus with a secondary dilatation of the renal pelvis and ureter. Because the patient was obese, the uterus and ovaries could not be palpated clearly at pelvic examination. However, the pelvic lymph nodes were not enlarged and no ascites was detected. CA 125 and carcinoembryonic antigen levels were within normal limits, whereas the CA 15.3 level was slightly above normal (45 U/mL).

At laparotomy, a 7 × 7 × 3-cm cystic tumor was found in the right mesosalpinx, which was completely separated from the ovary, fallopian tube, uterus, colon, and bladder. A thorough examination of the abdominal and pelvic cavities at the time of operation revealed no evidence of tumor spread beyond the mesosalpinx. A complete removal of the cystic tumor was performed successfully with no rupture or spillage. The patient then underwent a total hysterectomy with bilateral salpingo-oophorectomy followed by omentectomy, appendicectomy, random peritoneal biopsies, and peritoneal washings. Direct palpation allowed the exclusion of a colonie tumor.

The pathologic examination showed a multilocular cystic mass with smooth inner and outer surfaces filled with a hemorrhagic fluid. Microscopic examination revealed large cysts lined by simple to multistratified, cuboidal to columnar epithelium with a more complex pattern of papillary fronds and coalescent tufts. In solid areas, between the large cysts, we noted glands of variable size and shape with round and angular contours that displayed disordered growth, which indicate a stromal invasion. Most of the glands were filled with mucus and lined by one cell layer that was focally discontinuous. Some nuclei were bland looking and others showed frank atypia with mitotic figures, but in the whole nuclear atypia were moderate (Figure 1). Large pools of mucus were dissecting the stroma and were associated with an abundant polymorphous inflammatory infiltrate that consisted of giant cells with cholesterol clefts alongside lymphocytes, histiocytes, and plasma cells (Figure 2). Immunohistochemical analysis demonstrated a strong and diffuse positivity for both cytokeratin 7 (Figure 3) and epithelial membrane antigen (80%-90% of the cells). Less extensive staining with carcinoembryonic antigen (approximately 60% of tumor cells) and a focal unequivocal positivity with cytokeratin 20, specifically in mucinsecreting cells (5% of tumor cells) (Figure 4), were also observed.

Both ovaries and the fallopian tube were grossly and histologically normal. Neither pelvic endometriosis nor metastases in the omentum, peritoneum, and/or appendix were noted. Peritoneal washings were negative for malignant cells.

We diagnosed low-grade cystadenocarcinoma with a mucinous component of the broad ligament. Postoperative chemotherapy was conducted for 6 months using cisplatinum and cyclophosphamide. During the last month of treatment, a pelvic scan revealed a recurrent tumor, which was irradiated (30 Gy).

COMMENT

In 1977, Gardner et al7 proposed criteria for primary carcinoma of the broad ligament, namely a primary location within or on the surface of the broad ligament and a complete separation of the tumor from the uterus, ipsilateral ovary, and fallopian tube. When these stringent criteria are applied, primary carcinoma of the broad ligament becomes extremely rare; to our knowledge, only 18 cases have been reported in the literature.1,6 In approximate order of frequency, endometrioid, serous, and clear cell carcinoma are the most reported carcinomas, whereas only one case of mucinous cystadenocarcinoma was previously reported by Clark et al8 and revised by Aslani and Scully.1 The mean age of patients with these neoplasms is 46 years (range, 29-70 years).1,6 Unlike ovarian carcinoma, which occurs mainly during the sixth and seventh decades of life, these tumors tend to be diagnosed during the reproductive period.9

Clinical manifestations are similar to those of ovarian tumors.1,9 Although most of the tumors are well demarcated, pelvic adhesions and distant metastasis are possible at the time of diagnosis.1

The tumors, which vary in size from 5 to 13 cm in diameter, are always unilateral and can be solid, cystic, or both.1,3,6 Although there is little experience with the therapy of the broad ligament, follow-up data of the reported cases indicate that prognosis of these tumors is favorable, with an 80% to 90% 5-year survival rate and rare metastases.9 Their proximity to the ovary and the similar histologic features of the 2 types of tumor justify a management similar to that of an ovarian equivalent tumor.1 The one exception, however, relates to the differing laterality of ovarian and broad ligament carcinoma. In fact, ovarian carcinomas are bilateral in one third to half of the cases, whereas all the reported carcinomas of the broad ligament are unilateral.10 Therefore, for young women for whom preservation of reproductive function is desired, a wide local excision of a carcinoma confined to the broad ligament without removal of the adnexa or the uterus may be performed. An adjuvant chemotherapy regimen should be the same as the one used for ovarian carcinomas of similar histologie types.1,3 In our case, the early recurrence could be related to the mucinous type of the tumor. The extreme rarity of broad ligament carcinoma could be related to a misdiagnosis in advanced cases, where the whole adnexa is invaded by the tumor, which looks like an ovarian carcinoma. However, nonextensive tumors are also rare, which raises questions about their origin.

Although an accessory ovary or fallopian tube may be postulated as being the origin of these tumors,11,12 most authors agree that these and paraovarian tumors are presumed to originate from the wolffian (mesonephric), mullerian (paramesonephric), or mesothelial tissues.1-3 Some authors relied on the existence of smooth muscle cells to prove the mullerian origin of these tumors.13 In our observation, because smooth cells were absent, we presume that they could be invaded by tumor cells or otherwise embedded in the stroma reaction. As described in previous reports, we believe that mullerian and wolffian tumors are morphologically distinct and that glandular and cystic growths are particularly characteristic of wolffian tumors.14 The originality of our observation lies in the fact that the mucinous component with abundant mucus production mimics the one observed in pseudomyxoma peritonei, whereas both the ovary and appendix were normal. Colonie metastasis was excluded because of the absence of putative primary organs at the operation and the normality of the carcinoembryonic antigen level. The second striking point in our observation, as reported by Rojansky et al,9 is the extensive stroma reaction with lipid phagocytosis. Immunohistochemical analysis results were typical of a mullerian-type tumor with positivity of epithelial membrane antigen and carcinoembryonic antigen, which contrasts with their negativity in wolffian tumors.13,14 To our knowledge, cytokeratins 7 and 20 have not been studied in previous reports. Diffuse positivity of cytokeratin 7 is expected in this tumor, whereas focal positivity of cytokeratin 20 in mucin-secreting cells, an antigen usually positive in intestinal-type cells, could indicate a metaplastic process toward colonic phenotype and therefore explain the extreme rarity of the primary mucinous broad ligament.

References

1. Aslani M, Scully RE. Primary carcinoma of the broad ligament: report of four cases and review of literature. Cancer. 1989:64:1540-1545.

2. Loverro G, Cormio C, Renzulli C, Lepera A, Ricco R, Selvaggi L. Serous papillary cystadenoma of borderline malignancy of the broad ligament, Eur I Obstet Gynecol Reprod Biol. 1997;74:211-213.

3. Kobayashi Y, Yamazaki K, Shinohara M, et al. Undifferentiated carcinoma of the broad ligament in a 28-year old woman: a case report and results of immunohistochemical and electron-microscopic studies. Gynecol Oncol. 1996;63:382-387.

4. Shone N, Duggan MA, Ghatage P. Granulosa cell tumour of the broad ligament. Pathology. 2003;35:265-267.

5. Shah A, Finn C, Light A. Leiomyosarcoma of the broad ligament: a case report and literature review. Gynecol Oncol. 2003;90:450-452.

6. Itani Y, Itoh K, Adachi S, et al. Malignant epithelial tumor of unknown origin of the broad ligament. Arch Gynecol Obstet. 2002;267:113-116.

7. Gardner GH, Greene RR, Pecham BM. Tumors of the broad ligament. Am Obstet Gynecol. 1977;129:873-880.

8. Clark JE, Wood H, Jaffurs WJ, Fabro S. Endometrioid-type cystadenocarcinoma arising in the mesosalpinx. Obstet Gynecol. 1979;54:656-658.

9. Rojansky N, Ophir E, Sharony A, Spira H, Suprun H. Broad ligament adenocarcinoma: its origin and clinical behavior: a literature review and report of a case. Obstet Gynecol Surv. 1985:40:665-671.

10. Scully RE, Young RH, Clement PB. Tumors of the Ovary and Maldeveloped Gonads: Fallopian Tube and Broad Ligament. Washington, DC: Armed Forces Institute of Pathology; 1996. Atlas ot Tumor Pathology, 3rd series, fascicle 23.

11. Samaha M, Woodruff ID. Paratubal cysts: frequency, histogenesis and associated clinical features. Otefer Gynecol. 1985;65:691-694.

12. Roth LM, Davis MM, Sutton GP. Steroid cell tumor of the broad ligament arising in an accessory ovary. Arch Pathol Lab Med. 1996:120:405-409.

13. Tavassoli FA, Andrade R, Merino M. Retiform wolffian adenoma. In: Fenoglio-Preiser CM, Wolffe M, Rilke F, eds. Progress in Surgical Pathology. VoI 11. New York, NY: Field & Wood Medical Publishers; 1990:121-136.

14. Rahilly MA, Williams AR, Krausz T, AI-Naffussi AL. Female adnexal tumor of probable wolfiian origin: a clinicopathological and immunohistochemical study of three cases. Histopathology. 1995:26:69-74.

Karima Mrad, MD; Maha Driss, MD; Salma Abdelmoula, MD; Samia Sassi, MD; Monia Hechiche, MD; Khaled Ben Romdhane, MD

Accepted for publication September 21, 2004.

From the Departments of Pathology (Drs Mrad, Driss, Abdelmoula, Sassi, and Romdhane) and Surgical Oncology (Dr Hechiche), Institut Salah Azaiez, Tunis, Tunisia.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Karima Mrad, MD, Institut Salah Azaiez, Service d'Anatomie et cytologie Pathologiques, 1006 BabSaadoun, Tunis, Tunisia (e-mail: karima.mrad@rns.tn).

Copyright College of American Pathologists Feb 2005
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