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Wolffian Duct Tumors: Case Reports and Review of the Literature
Gynecologic Oncology 86, 225–230 (2002) doi:10.1006/gyno.2002.6739
CASE REPORT Wolffian Duct Tumors: Case Reports and Review of the Literature Pedro T. Ramirez, M.D.,* ,1 Judith K. Wolf, M.D.,* Anais Malpica, M.D.,† Michael T. Deavers, M.D.,† Jinsong Liu, M.D., Ph.D.,† and Russell Broaddus, M.D., Ph.D.† *Department of Gynecologic Oncology and †Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 Received January 2, 2002
Background. Female adnexal tumors of probable wolffian origin are a distinctive epithelial neoplasm arising from the remnants of the mesonephric duct. Although generally considered a tumor of low malignant potential, these tumors can recur. Two cases are reported here. Cases. (1) A 38-year-old G 6P 6 Latin American woman presented with lower abdominal pain and a pelvic mass. She had a history of a total abdominal hysterectomy and bilateral salpingo-oophorectomy with a paratubal nodule found incidentally 3 years prior. The pathologic findings were consistent with a female adnexal tumor of probable wolffian origin. Imaging studies revealed significant metastatic disease throughout her abdomen and pelvis. The recurrence was confirmed at laparotomy and tumor debulking was performed. Four months later the patient suffered a second recurrence and is currently undergoing treatment with systemic therapy. (2) A 71-year-old Caucasian woman who had undergone exploratory laparotomy and tumor reductive surgery for a female adnexal tumor of probable wolffian duct origin was seen for routine evaluation 1 year after her surgery. Her computed tomography scan revealed possible evidence of recurrence. Conclusion. Most female adnexal tumors of wolffian origin behave in a benign fashion. However, there is a potential risk of recurrence. Surgical excision by total abdominal hysterectomy and bilateral salpingo-oophorectomy at the time of diagnosis may be the best recommended mode of therapy. The role of adjuvant radiation therapy or chemotherapy remains questionable. © 2002 Elsevier Science (USA)
INTRODUCTION Female adnexal tumors of probable wolffian origin were first described by Kariminejad and Scully in 1973 [1]. A total of 69 cases have been documented thus far in the literature. This rare neoplasm usually arises in the leaves of the broad ligament or a fallopian tube. Generally these tumors are thought to have a 1
To whom correspondence and reprint requests should be addressed at Department of Gynecologic Oncology, Box 440, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Fax: (713) 792-7586. E-mail: [email protected]. 225
low malignant potential, since only 8 patients have shown evidence of recurrence. Because of the limited number of cases, the recommended approach to the initial evaluation, management, and subsequent follow-up in these patients remains elusive. CASE REPORT Case 1 A 38-year-old G 6P 6 Latin American woman presented in August 2001 with a 3-week history of lower abdominal pain, an enlarging abdominal mass, and constipation. Her surgical history was significant for a total abdominal hysterectomy for menometrorrhagia performed in 1998. At operation, a leiomyomatous uterus was found, and a right paratubal nodule was also removed. Pathologic analysis revealed that the nodule was a female adnexal tumor of probable wolffian origin. The patient did not undergo further therapy. During the current presentation the physical examination did not show any evidence of adenopathy. Abdominal examination revealed a large palpable mass measuring 14 ⫻ 16-cm that arose from the pelvis. A chest radiograph did not reveal any evidence of intrathoracic metastases. A computed tomographic (CT) scan showed a heterogeneous partially cystic and solid pelvic mass. Large bulky implants were noted in the liver capsule of the right hepatic lobe posteriorly and laterally. A capsular splenic implant was also noted. Her serum CA-125 level was 286 U/ml (normal, ⬍35 U/ml). The patient underwent exploratory laparotomy and optimal tumor reductive surgery. The intraoperative findings revealed a 16 ⫻ 18-cm, irregular mass arising in the pelvis. Both ovaries were unremarkable. There was a 3 ⫻ 4-cm omental nodule in the region of the splenic flexure. The spleen was free of disease. There were also multiple perihepatic masses as described on the CT scan. Pelvic washings, lysis of adhesions, excision of pelvic mass, bilateral salpingo-oophorectomy, omentectomy, excision of perihepatic masses, and appendectomy were performed. There was no evidence of macroscopic 0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.
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FIG. 1.
Lobulated tumor mass with areas of hemorrhage and necrosis.
disease at the completion of the surgery. The patient’s postoperative course was uneventful, and she was discharged on day 6 after her surgery. Cytologic analysis of her ascitic fluid showed metastatic tumor. A malignant epithelial neoplasm of probable wolffian origin was documented in the pelvic mass (17.0 ⫻ 12.0 ⫻ 7.5 cm), omental nodule, and perihepatic implants (Fig. 1). Both ovaries and the appendix were free of tumor. The morphologic features of the neoplasm were similar to those of the patient’s prior tumor. Immunohistochemical staining showed the neoplasm was positive for inhibin, calretinin, and focally for cytokeratin 7. It stained negatively for epithelial membrane antigen (EMA). Electron microscopy demonstrated epithelial differentiation with short microvilli. Immunohistochemistry studies were done to determine the estrogen receptor (ER) and progesterone receptor (PR) and c-kit and Her2/neu statuses. The tumor was positive for progesterone receptors only. No adjuvant therapy was recommended at the time. Four months later the patient presented with a palpable right anterior abdominal wall mass measuring 3 ⫻ 4-cm. There were also multiple nodular densities noted on pelvic examination. A repeat CT scan showed a 10 ⫻ 7-cm mass in the liver parenchyma, a 5-cm mass in the left upper quadrant, a 6 ⫻ 8-cm mass in the spleen, multiple 2-cm nodules in the pelvis, and a 2-cm subcutaneous nodule on the right anterior abdominal wall. Her serum CA-125 was 46 U/ml. The patient was treated with three courses of carboplatinum (AUC 5) and paclitaxel (175 mg/m 2) and one dose of intramuscular leuprolide (22.5 mg). At the completion of this regimen, she was noted to have progressive disease.
Case 2 A 71-year-old Caucasian woman was initially seen in October 2000 because of a pelvic mass found incidentally on examination. The patient was completely asymptomatic. Her surgical history was significant for a total abdominal hysterectomy and bilateral salpingo-oophorectomy performed in 1967 for a leiomyomatous uterus. Physical examination did not reveal any evidence of adenopathy. Her abdomen was soft and mildly distended. Pelvic examination showed multiple nodular lesions measuring approximately 4 ⫻ 6-cm. A chest radiograph did not reveal any evidence of malignancy. CT scans of the abdomen and pelvis showed multiple lesions with enhancing capsules within the pelvis, suggestive of ovarian malignancy. Her serum CA-125 level was 13 U/ml, and her carcinoembryonic antigen (CEA) level was 1.5 ng/ml. The patient underwent exploratory laparotomy, omentectomy, and tumor reductive surgery. At surgery, a multiloculated tumor (16.0 ⫻ 12.0 ⫻ 5.0 cm) was found that filled the pelvis and extended along the left pelvic sidewall. Multiple nodules were noted along the mesentery of the large bowel. Optimal tumor debulking was achieved and no macroscopic disease was present at the conclusion of the surgery. The patient’s postoperative course was uneventful and she was discharged 6 days after her surgery. The final pathology report described a neoplasm with spindled and epithelioid cells of probable wolffian origin involving the pelvis, mesentery, and omentum. Immunohistochemical staining was positive for calretinin, cytokeratin, and Moc31 and focally positive for CK5/6. The staining was negative for
CASE REPORT
inhibin, B72.3, CK20, S-100 protein, EMA, and p53. The tumor showed strong nuclear staining for ER and PR receptors in approximately 80% of the tumor cells. c-Kit and Her-2/ neu staining was entirely negative. No further treatment was offered. The patient was then seen in August 2001 for routine evaluation. She was asymptomatic, and her examination was unremarkable. However, CT scans showed a new nodule in the left upper pelvis adjacent to the sigmoid colon consistent with a new peritoneal implant. There was also an implant at the liver margin. Her serum CA-125 level was ⬍7 U/ml. At the time, these areas were not considered suitable for biopsy. The patient underwent repeat CT scans in March 2002 and the findings were unchanged. DISCUSSION The mesonephric ducts and tubules begin to develop into a primitive urinary system in the fourth week of embryonic life. In the male, the mesonephric (wolffian duct) system is appropriated by the reproductive system, while in the female the mesonephric tubules and ducts degenerate [2]. Only remnants of the wolffian duct persist in adults in the form of such structures as hydatids of Morgagni and Gartner’s cysts [3]. In evaluating structures in the normal adult broad ligament, Gardner et al. [4] suggested three major differences between wolffian and Mu¨ llerian structures: (1) wolffian epithelial cells and nuclei are significantly smaller than those of Mu¨ llerian cysts; (2) wolffian ducts and tubules have a better-defined basement membrane; and (3) wolffian epithelium does not respond to cyclical hormonal stimulation, as does Mu¨ llerian epithelium. In their original description published in 1973, Kariminejad and Scully [1] defined a new classification of tumors designated “female adnexal tumors of probable wolffian origin.” Although the diagnosis of this tumor is based on the exclusion of other possibilities, these tumors do not otherwise closely resemble any neoplasm arising from either a Mu¨ llerian duct derivative or the surface epithelium of the ovary. The nomenclature was assigned because these tumors are primarily located in a site with abundant wolffian remnants. Grossly these tumors range in size from 0.8 to 25 cm. Typically they have a solid, ovoid mass, bosselated, nodular, or lobulated appearance. Most tumors are encapsulated with a smooth, glistening, pale yellow or a light gray external surface. Occasionally, the tumors are focally hemorrhagic with central cystic necrosis. Characteristic histopathologic patterns found on microscopic examination include a solid or diffuse arrangement of the neoplastic epithelial cells; closely packed, winding, branching, and anastomosing tubules, which are slender and solid or have peripheral nuclei and central cytoplasm; and a sieve-like pattern with hollow tubules varying in size and shape with occasional cysts. The stroma of the tumor varies from a deli-
227
cate network of reticulin fibers separating the solid tubules to large areas of hyalinized collagen [1] (Fig. 2). In a subsequent report, Taxy and Battifora [5] described the characteristic electron microscopy findings. They noted that the nuclei of the tumor cells had evenly distributed chromatin and were large and irregular in shape due to prominent folds and clefts. Cytoplasmic organelles included free ribosomes, well-developed Golgi regions, and randomly distributed round-to-tubular mitochondria with increased matrix. Rahilly et al. [6] performed a comparative immunohistochemical analysis of female adnexal tumors of probable wolffian origin and found several tumor profiles. They noted that these tumors coexpressed cytokeratins (CAM 5.2 and PKK1) and vimentin and stained positive for S-100 protein. In addition, they showed that reactivity for EMA is not a diagnostic finding, since it is expressed variably in wolffian duct tumors. In a larger study of 25 cases, Devouassoux-Shisheboran et al. [7] found that female adnexal tumors of probable wolffian origin were immunoreactive for pancytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (88%), keratin 903 (17%), EMA (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). The tumors were not reactive for monoclonal CEA or for cytokeratin 20. These tumors can arise anywhere along the trajectory of the wolffian duct, which extends from the hilum of the ovary, along the mesosalpinx and the lateral aspects of the uterus, to the outer third of the vagina [8]. Young and Scully [9] reported on a series of 11 patients whose tumors arose in the ovary. Subsequently, Daya et al. [10] reported on 6 cases of fallopian tube endometrioid carcinoma resembling adnexal tumors of probable wolffian origin. This author later reported on a similar tumor found in the paravaginal region [11]. The main differential diagnoses include Sertoli–Leydig cell tumors, clear cell tumors, and granulosa cell tumors. Wolffian tumors can be differentiated from Sertoli–Leydig cell tumors by the fact that the latter tend to be multi-insular or even lobulated, with cellular and differentiated zones separated by poorly cellular, featureless areas. These characteristics are lacking in wolffian duct tumors [12]. On the other hand, a lack of stromal cells of the steroid-hormone-secreting type, consistent with Leydig cells argues against a diagnosis of Sertoli– Leydig cell tumor [9]. Clear cell carcinomas can be differentiated from wolffian duct tumors by the fact that clear cell tumors contain one or more of the following features: solid aggregates of clear cells, papillary areas, well-developed hobnail cells, and intraluminal mucin [9]. Granulosa cell tumors may mimic tumors of wolffian duct origin. However, cytologic differences, such as grooved nuclei and scanty cytoplasm, and the lack of endocrine manifestations will exclude a wolffian duct tumor as a possible diagnosis [6]. Including our 2 patients, a total of 71 pathologically documented cases have now been reported. We reviewed the clinical and pathologic information on all of these cases. The
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FIG. 2. Photomicrographs of the two wolffian duct tumors in this report. H&E, 200⫻. (A) Patient 1. This tumor was characterized by epithelioid areas with clear cytoplasm as well as more splindled areas. (B) Patient 2. This tumor was predominantly composed of spindled cells with only focal epithelioid differentiation.
median age of the patients was 50 years (range, 18 to 83 years). Gravidy and parity status was documented in 16 patients. The median gravidy was 3 (range, 0 to 8), and the median parity was 2 (range, 0 to 8). The presentation and symptomatology were documented in 66 patients. The tumor was an incidental finding in 35 of these 66 patients (53%). The most common complaint was abdominal/pelvic pain (20 of 66 patients, 30%),
followed by abdominal swelling (11 of 66 patients, 17%), vaginal bleeding (9 of 66 patients, 14%), constipation (2 of 66 patients, 3%), urinary frequency (1 of 66 patients, 2%), weight loss (1 of 66 patients, 2%), and tenesmus (1 of 66 patients, 2%). Tumor marker studies were not routinely performed. Including our two patients, a total of five patients [13–15] had documentation of CA-125 levels measured preoperatively and
229
CASE REPORT
all of these were normal. Our first patient did have an elevated serum CA-125 level, but only at the time of recurrence. In one report [13], a patient was described in whom other markers, such as CA19-9, CA72-4, CEA, and ␣-fetoprotein were measured, but all levels were normal. Inoue et al. [14] looked at the hormonal function of wolffian duct tumors and found that these tumors might be endocrinologically active by virtue of the fact that serum levels of estradiol and testosterone were elevated preoperatively but decreased after tumor reductive surgery. To our knowledge, our two patients were the first to have ER and PR receptor status and c-kit and Her2/neu evaluation. Imaging study findings were described in six reports [13– 18], besides those in our two patients described here. CT scanning typically shows well demarcated, multilocular tumors, with an irregularly enhancing capsule indicating a malignant potential. Ultrasonography shows a hypoechoic and homogeneous component surrounded by a thick capsule. Magnetic resonance imaging shows a well-defined, ovoid mass. T-2-weighted images show a hyperintense mass with a central cystic component. On gadolinium-enhanced T-1-weighted images, apart from the cystic element, the mass enhances homogeneously. The surgical procedures performed were reported for 45 patients. The most common procedure was total abdominal hysterectomy with bilateral salpingo-oophorectomy. This was followed by tumor reductive surgery/cystectomy, unilateral adnexectomy, bilateral adnexectomy, and least frequently, total abdominal hysterectomy with or without andexectomy (Table 1). Six patients received postoperative treatment [5, 12, 15, 16, 19, 20]. Three were treated with radiation therapy, and three were treated with platinum-based chemotherapy. Follow-up ranged from 10 days to 20 years. During this follow-up period, disease recurred in eight patients. The median time to recurrence was 48 months (range, 13 to 96 months). Table 2 gives the sites of recurrence [2, 5, 9, 11, 15, 21, 22]. Of note, five of the eight patients who suffered a recurrence were treated initially with procedures other than a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Certain tumor characteristics have been identified that are associated with an increased risk for tumor recurrence; these
TABLE 1 Procedures Performed at Diagnosis Procedure
No.
TAH/BSO TAH ⫾ USO BSO USO Tumor enucleation/cystectomy Not specified
22 3 5 7 8 26
Note. TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; USO, unilateral salpingo-oophorectomy.
TABLE 2 Site and Time to Recurrence Site
No. (%)
Median time (months)
Upper abdomen/pelvis Abdomen alone Liver Pelvis alone Lungs
2 (25) 2 (25) 2 (25) 1 (12) 1 (12)
54 22 48 13 96
include hypercellularity, cellular pleomorphism, and an increased number of mitotic figures. However, tumors with minimal nuclear atypia and a very low mitotic rate may also recur [13]. Of the three patients treated with adjuvant radiation therapy, one had recurrence. Of the three patients treated with adjuvant chemotherapy, one had recurrence. Surgical resection is the current recommended treatment for recurrent tumors. Given the small number of cases, there are no current recommendations regarding adjuvant or salvage therapy. Initial surgery in the form of total abdominal hysterectomy and bilateral salpingo-oophorectomy should remain the most likely treatment for this rare tumor. However, patient characteristics such as age and desire for fertility should certainly be considered when formulating a treatment plan. The role for adjuvant chemotherapy or radiation therapy remains questionable. REFERENCES 1. Kariminejad MH, Scully RE. Female adnexal tumor of probable wolffian origin. Cancer 1973;31:671–7. 2. Abbot RL, Barlogie B, Schmidt WA. Metastasizing malignant juxtaovarian tumor with terminal hypercalcermia: a case report. Cancer 1981;48: 860 –5. 3. Sadler TW. Langman’s medical embryology. 5th ed. Baltimore, MD: Williams & Wilkins, 1989:258 – 68. 4. Gardner GH, Greene RR, Peckham B. Tumors of the broad ligament. Am J Obstet Gynecol 1957;73:536 –54. 5. Taxy JB, Battifora H. Female adnexal tumor of probable wolffian origin: evidence of a low-grade malignancy. Cancer 1976;37:2349 –54. 6. Rahilly MA, Williams ARW, Krausz T, Nafussi AA. Female adnexal tumor of probable wolffian origin: a clinicopathological and immunohistochemical study of three cases. Histopathology 1995;26:69 –74. 7. Devouassoux-Shisheboran M, Silver SA, Tavassoli FA. Wolffian adnexal tumor, so-called female adnexal tumor of probable wolffian origin (FATWO): immunohistochemical evidence in support of a wolffian origin. Hum Pathol 1999;30:856 – 63. 8. Moore KL. The developing human: clinically oriented embryology. 4th ed. Philadelphia: Saunders, 1988:246 – 83. 9. Young RH, Scully RE. Ovarian tumors of probable wolffian origin: a report of 11 cases. Am J Surg Pathol 1983;7:125–35. 10. Daya D, Young RH, Scully RE. Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: a report of six cases. Int J Gynecol Pathol 1992;11:122–30. 11. Daya D, Murphy J, Simon G. Paravaginal female adnexal tumor of probable wolffian origin. Am J Clin Pathol 1994;101:275– 8
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12. Sivathondan Y, Salm R, Hughesdon PE, Faccini JM. Female adnexal tumor of probable wolffian origin. J Clin Pathol 1979;32:616 –24. 13. Wagatsuma S, Yaegashi N, Namiki T, Sato S, Yajima A. A case of female adnexal tumor of probable wolffian origin: histologically, tumor cells showed three different patterns. Tohoku J Exp Med 1997;181:371–7. 14. Inoue H, Kikuchi Y, Hori T, Nabuchi K, Kobayashi M, Nagata I. An ovarian tumor of probable wolffian origin with hormonal function. Gynecol Oncol 1995;59:304 – 8. 15. Sheyn I, Mira JL, Bejarano PA, Husseinzadeh N. Metastatic female adnexal tumor of probable wolffian origin: a case report and review of the literature. Arch Pathol Lab Med 2000;124:431– 4. 16. Hinchey WW, Silva EG, Guarda LA, Ordonez NG, Wharton JT. Paravaginal wolffian duct (mesonephros) adenocarcinoma: a light and electron microscopic study. Am J Clin Pathol 1983;80:539 – 44 .
17. Bata MS, Kamal MF. Female adnexal tumour of probable wolffian origin in a 23-year-old woman. Eur J Obstet Gynecol Reprod Biol 1999;87:179– 82. 18. Matsuki M, Kaji Y, Matsuo M. Female adnexal tumour of probable wolffian origin: MR findings. Br J Radiol 1999;72:911–3. 19. Flanagan AM, Kane JL, Norman-Taylor JQ. Female adnexal tumour of probable wolffian origin: case report. Br J Obstet Gynecol 1987;94:270 –2. 20. Prasad CJ, Ray JA, Kessler S. Female adnexal tumor of wolffian origin. Arch Pathol Lab Med 1992;116:189 –91. 21. Hughesdon PE. Ovarian tumours of wolffian or allied nature: their place in ovarian oncology. J Clin Pathol 1982;35:526 –35. 22. Brescia RJ, Cardoso de Almeida PC, Fuller AF, Dickersin GR, Robboy SJ. Female adnexal tumor of probable wolffian origin with multiple recurrences over 16 years. Cancer 1985;56:1456 – 61
CASE REPORT Wolffian Duct Tumors: Case Reports and Review of the Literature Pedro T. Ramirez, M.D.,* ,1 Judith K. Wolf, M.D.,* Anais Malpica, M.D.,† Michael T. Deavers, M.D.,† Jinsong Liu, M.D., Ph.D.,† and Russell Broaddus, M.D., Ph.D.† *Department of Gynecologic Oncology and †Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 Received January 2, 2002
Background. Female adnexal tumors of probable wolffian origin are a distinctive epithelial neoplasm arising from the remnants of the mesonephric duct. Although generally considered a tumor of low malignant potential, these tumors can recur. Two cases are reported here. Cases. (1) A 38-year-old G 6P 6 Latin American woman presented with lower abdominal pain and a pelvic mass. She had a history of a total abdominal hysterectomy and bilateral salpingo-oophorectomy with a paratubal nodule found incidentally 3 years prior. The pathologic findings were consistent with a female adnexal tumor of probable wolffian origin. Imaging studies revealed significant metastatic disease throughout her abdomen and pelvis. The recurrence was confirmed at laparotomy and tumor debulking was performed. Four months later the patient suffered a second recurrence and is currently undergoing treatment with systemic therapy. (2) A 71-year-old Caucasian woman who had undergone exploratory laparotomy and tumor reductive surgery for a female adnexal tumor of probable wolffian duct origin was seen for routine evaluation 1 year after her surgery. Her computed tomography scan revealed possible evidence of recurrence. Conclusion. Most female adnexal tumors of wolffian origin behave in a benign fashion. However, there is a potential risk of recurrence. Surgical excision by total abdominal hysterectomy and bilateral salpingo-oophorectomy at the time of diagnosis may be the best recommended mode of therapy. The role of adjuvant radiation therapy or chemotherapy remains questionable. © 2002 Elsevier Science (USA)
INTRODUCTION Female adnexal tumors of probable wolffian origin were first described by Kariminejad and Scully in 1973 [1]. A total of 69 cases have been documented thus far in the literature. This rare neoplasm usually arises in the leaves of the broad ligament or a fallopian tube. Generally these tumors are thought to have a 1
To whom correspondence and reprint requests should be addressed at Department of Gynecologic Oncology, Box 440, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Fax: (713) 792-7586. E-mail: [email protected]. 225
low malignant potential, since only 8 patients have shown evidence of recurrence. Because of the limited number of cases, the recommended approach to the initial evaluation, management, and subsequent follow-up in these patients remains elusive. CASE REPORT Case 1 A 38-year-old G 6P 6 Latin American woman presented in August 2001 with a 3-week history of lower abdominal pain, an enlarging abdominal mass, and constipation. Her surgical history was significant for a total abdominal hysterectomy for menometrorrhagia performed in 1998. At operation, a leiomyomatous uterus was found, and a right paratubal nodule was also removed. Pathologic analysis revealed that the nodule was a female adnexal tumor of probable wolffian origin. The patient did not undergo further therapy. During the current presentation the physical examination did not show any evidence of adenopathy. Abdominal examination revealed a large palpable mass measuring 14 ⫻ 16-cm that arose from the pelvis. A chest radiograph did not reveal any evidence of intrathoracic metastases. A computed tomographic (CT) scan showed a heterogeneous partially cystic and solid pelvic mass. Large bulky implants were noted in the liver capsule of the right hepatic lobe posteriorly and laterally. A capsular splenic implant was also noted. Her serum CA-125 level was 286 U/ml (normal, ⬍35 U/ml). The patient underwent exploratory laparotomy and optimal tumor reductive surgery. The intraoperative findings revealed a 16 ⫻ 18-cm, irregular mass arising in the pelvis. Both ovaries were unremarkable. There was a 3 ⫻ 4-cm omental nodule in the region of the splenic flexure. The spleen was free of disease. There were also multiple perihepatic masses as described on the CT scan. Pelvic washings, lysis of adhesions, excision of pelvic mass, bilateral salpingo-oophorectomy, omentectomy, excision of perihepatic masses, and appendectomy were performed. There was no evidence of macroscopic 0090-8258/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.
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RAMIREZ ET AL.
FIG. 1.
Lobulated tumor mass with areas of hemorrhage and necrosis.
disease at the completion of the surgery. The patient’s postoperative course was uneventful, and she was discharged on day 6 after her surgery. Cytologic analysis of her ascitic fluid showed metastatic tumor. A malignant epithelial neoplasm of probable wolffian origin was documented in the pelvic mass (17.0 ⫻ 12.0 ⫻ 7.5 cm), omental nodule, and perihepatic implants (Fig. 1). Both ovaries and the appendix were free of tumor. The morphologic features of the neoplasm were similar to those of the patient’s prior tumor. Immunohistochemical staining showed the neoplasm was positive for inhibin, calretinin, and focally for cytokeratin 7. It stained negatively for epithelial membrane antigen (EMA). Electron microscopy demonstrated epithelial differentiation with short microvilli. Immunohistochemistry studies were done to determine the estrogen receptor (ER) and progesterone receptor (PR) and c-kit and Her2/neu statuses. The tumor was positive for progesterone receptors only. No adjuvant therapy was recommended at the time. Four months later the patient presented with a palpable right anterior abdominal wall mass measuring 3 ⫻ 4-cm. There were also multiple nodular densities noted on pelvic examination. A repeat CT scan showed a 10 ⫻ 7-cm mass in the liver parenchyma, a 5-cm mass in the left upper quadrant, a 6 ⫻ 8-cm mass in the spleen, multiple 2-cm nodules in the pelvis, and a 2-cm subcutaneous nodule on the right anterior abdominal wall. Her serum CA-125 was 46 U/ml. The patient was treated with three courses of carboplatinum (AUC 5) and paclitaxel (175 mg/m 2) and one dose of intramuscular leuprolide (22.5 mg). At the completion of this regimen, she was noted to have progressive disease.
Case 2 A 71-year-old Caucasian woman was initially seen in October 2000 because of a pelvic mass found incidentally on examination. The patient was completely asymptomatic. Her surgical history was significant for a total abdominal hysterectomy and bilateral salpingo-oophorectomy performed in 1967 for a leiomyomatous uterus. Physical examination did not reveal any evidence of adenopathy. Her abdomen was soft and mildly distended. Pelvic examination showed multiple nodular lesions measuring approximately 4 ⫻ 6-cm. A chest radiograph did not reveal any evidence of malignancy. CT scans of the abdomen and pelvis showed multiple lesions with enhancing capsules within the pelvis, suggestive of ovarian malignancy. Her serum CA-125 level was 13 U/ml, and her carcinoembryonic antigen (CEA) level was 1.5 ng/ml. The patient underwent exploratory laparotomy, omentectomy, and tumor reductive surgery. At surgery, a multiloculated tumor (16.0 ⫻ 12.0 ⫻ 5.0 cm) was found that filled the pelvis and extended along the left pelvic sidewall. Multiple nodules were noted along the mesentery of the large bowel. Optimal tumor debulking was achieved and no macroscopic disease was present at the conclusion of the surgery. The patient’s postoperative course was uneventful and she was discharged 6 days after her surgery. The final pathology report described a neoplasm with spindled and epithelioid cells of probable wolffian origin involving the pelvis, mesentery, and omentum. Immunohistochemical staining was positive for calretinin, cytokeratin, and Moc31 and focally positive for CK5/6. The staining was negative for
CASE REPORT
inhibin, B72.3, CK20, S-100 protein, EMA, and p53. The tumor showed strong nuclear staining for ER and PR receptors in approximately 80% of the tumor cells. c-Kit and Her-2/ neu staining was entirely negative. No further treatment was offered. The patient was then seen in August 2001 for routine evaluation. She was asymptomatic, and her examination was unremarkable. However, CT scans showed a new nodule in the left upper pelvis adjacent to the sigmoid colon consistent with a new peritoneal implant. There was also an implant at the liver margin. Her serum CA-125 level was ⬍7 U/ml. At the time, these areas were not considered suitable for biopsy. The patient underwent repeat CT scans in March 2002 and the findings were unchanged. DISCUSSION The mesonephric ducts and tubules begin to develop into a primitive urinary system in the fourth week of embryonic life. In the male, the mesonephric (wolffian duct) system is appropriated by the reproductive system, while in the female the mesonephric tubules and ducts degenerate [2]. Only remnants of the wolffian duct persist in adults in the form of such structures as hydatids of Morgagni and Gartner’s cysts [3]. In evaluating structures in the normal adult broad ligament, Gardner et al. [4] suggested three major differences between wolffian and Mu¨ llerian structures: (1) wolffian epithelial cells and nuclei are significantly smaller than those of Mu¨ llerian cysts; (2) wolffian ducts and tubules have a better-defined basement membrane; and (3) wolffian epithelium does not respond to cyclical hormonal stimulation, as does Mu¨ llerian epithelium. In their original description published in 1973, Kariminejad and Scully [1] defined a new classification of tumors designated “female adnexal tumors of probable wolffian origin.” Although the diagnosis of this tumor is based on the exclusion of other possibilities, these tumors do not otherwise closely resemble any neoplasm arising from either a Mu¨ llerian duct derivative or the surface epithelium of the ovary. The nomenclature was assigned because these tumors are primarily located in a site with abundant wolffian remnants. Grossly these tumors range in size from 0.8 to 25 cm. Typically they have a solid, ovoid mass, bosselated, nodular, or lobulated appearance. Most tumors are encapsulated with a smooth, glistening, pale yellow or a light gray external surface. Occasionally, the tumors are focally hemorrhagic with central cystic necrosis. Characteristic histopathologic patterns found on microscopic examination include a solid or diffuse arrangement of the neoplastic epithelial cells; closely packed, winding, branching, and anastomosing tubules, which are slender and solid or have peripheral nuclei and central cytoplasm; and a sieve-like pattern with hollow tubules varying in size and shape with occasional cysts. The stroma of the tumor varies from a deli-
227
cate network of reticulin fibers separating the solid tubules to large areas of hyalinized collagen [1] (Fig. 2). In a subsequent report, Taxy and Battifora [5] described the characteristic electron microscopy findings. They noted that the nuclei of the tumor cells had evenly distributed chromatin and were large and irregular in shape due to prominent folds and clefts. Cytoplasmic organelles included free ribosomes, well-developed Golgi regions, and randomly distributed round-to-tubular mitochondria with increased matrix. Rahilly et al. [6] performed a comparative immunohistochemical analysis of female adnexal tumors of probable wolffian origin and found several tumor profiles. They noted that these tumors coexpressed cytokeratins (CAM 5.2 and PKK1) and vimentin and stained positive for S-100 protein. In addition, they showed that reactivity for EMA is not a diagnostic finding, since it is expressed variably in wolffian duct tumors. In a larger study of 25 cases, Devouassoux-Shisheboran et al. [7] found that female adnexal tumors of probable wolffian origin were immunoreactive for pancytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (88%), keratin 903 (17%), EMA (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). The tumors were not reactive for monoclonal CEA or for cytokeratin 20. These tumors can arise anywhere along the trajectory of the wolffian duct, which extends from the hilum of the ovary, along the mesosalpinx and the lateral aspects of the uterus, to the outer third of the vagina [8]. Young and Scully [9] reported on a series of 11 patients whose tumors arose in the ovary. Subsequently, Daya et al. [10] reported on 6 cases of fallopian tube endometrioid carcinoma resembling adnexal tumors of probable wolffian origin. This author later reported on a similar tumor found in the paravaginal region [11]. The main differential diagnoses include Sertoli–Leydig cell tumors, clear cell tumors, and granulosa cell tumors. Wolffian tumors can be differentiated from Sertoli–Leydig cell tumors by the fact that the latter tend to be multi-insular or even lobulated, with cellular and differentiated zones separated by poorly cellular, featureless areas. These characteristics are lacking in wolffian duct tumors [12]. On the other hand, a lack of stromal cells of the steroid-hormone-secreting type, consistent with Leydig cells argues against a diagnosis of Sertoli– Leydig cell tumor [9]. Clear cell carcinomas can be differentiated from wolffian duct tumors by the fact that clear cell tumors contain one or more of the following features: solid aggregates of clear cells, papillary areas, well-developed hobnail cells, and intraluminal mucin [9]. Granulosa cell tumors may mimic tumors of wolffian duct origin. However, cytologic differences, such as grooved nuclei and scanty cytoplasm, and the lack of endocrine manifestations will exclude a wolffian duct tumor as a possible diagnosis [6]. Including our 2 patients, a total of 71 pathologically documented cases have now been reported. We reviewed the clinical and pathologic information on all of these cases. The
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FIG. 2. Photomicrographs of the two wolffian duct tumors in this report. H&E, 200⫻. (A) Patient 1. This tumor was characterized by epithelioid areas with clear cytoplasm as well as more splindled areas. (B) Patient 2. This tumor was predominantly composed of spindled cells with only focal epithelioid differentiation.
median age of the patients was 50 years (range, 18 to 83 years). Gravidy and parity status was documented in 16 patients. The median gravidy was 3 (range, 0 to 8), and the median parity was 2 (range, 0 to 8). The presentation and symptomatology were documented in 66 patients. The tumor was an incidental finding in 35 of these 66 patients (53%). The most common complaint was abdominal/pelvic pain (20 of 66 patients, 30%),
followed by abdominal swelling (11 of 66 patients, 17%), vaginal bleeding (9 of 66 patients, 14%), constipation (2 of 66 patients, 3%), urinary frequency (1 of 66 patients, 2%), weight loss (1 of 66 patients, 2%), and tenesmus (1 of 66 patients, 2%). Tumor marker studies were not routinely performed. Including our two patients, a total of five patients [13–15] had documentation of CA-125 levels measured preoperatively and
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CASE REPORT
all of these were normal. Our first patient did have an elevated serum CA-125 level, but only at the time of recurrence. In one report [13], a patient was described in whom other markers, such as CA19-9, CA72-4, CEA, and ␣-fetoprotein were measured, but all levels were normal. Inoue et al. [14] looked at the hormonal function of wolffian duct tumors and found that these tumors might be endocrinologically active by virtue of the fact that serum levels of estradiol and testosterone were elevated preoperatively but decreased after tumor reductive surgery. To our knowledge, our two patients were the first to have ER and PR receptor status and c-kit and Her2/neu evaluation. Imaging study findings were described in six reports [13– 18], besides those in our two patients described here. CT scanning typically shows well demarcated, multilocular tumors, with an irregularly enhancing capsule indicating a malignant potential. Ultrasonography shows a hypoechoic and homogeneous component surrounded by a thick capsule. Magnetic resonance imaging shows a well-defined, ovoid mass. T-2-weighted images show a hyperintense mass with a central cystic component. On gadolinium-enhanced T-1-weighted images, apart from the cystic element, the mass enhances homogeneously. The surgical procedures performed were reported for 45 patients. The most common procedure was total abdominal hysterectomy with bilateral salpingo-oophorectomy. This was followed by tumor reductive surgery/cystectomy, unilateral adnexectomy, bilateral adnexectomy, and least frequently, total abdominal hysterectomy with or without andexectomy (Table 1). Six patients received postoperative treatment [5, 12, 15, 16, 19, 20]. Three were treated with radiation therapy, and three were treated with platinum-based chemotherapy. Follow-up ranged from 10 days to 20 years. During this follow-up period, disease recurred in eight patients. The median time to recurrence was 48 months (range, 13 to 96 months). Table 2 gives the sites of recurrence [2, 5, 9, 11, 15, 21, 22]. Of note, five of the eight patients who suffered a recurrence were treated initially with procedures other than a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Certain tumor characteristics have been identified that are associated with an increased risk for tumor recurrence; these
TABLE 1 Procedures Performed at Diagnosis Procedure
No.
TAH/BSO TAH ⫾ USO BSO USO Tumor enucleation/cystectomy Not specified
22 3 5 7 8 26
Note. TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; USO, unilateral salpingo-oophorectomy.
TABLE 2 Site and Time to Recurrence Site
No. (%)
Median time (months)
Upper abdomen/pelvis Abdomen alone Liver Pelvis alone Lungs
2 (25) 2 (25) 2 (25) 1 (12) 1 (12)
54 22 48 13 96
include hypercellularity, cellular pleomorphism, and an increased number of mitotic figures. However, tumors with minimal nuclear atypia and a very low mitotic rate may also recur [13]. Of the three patients treated with adjuvant radiation therapy, one had recurrence. Of the three patients treated with adjuvant chemotherapy, one had recurrence. Surgical resection is the current recommended treatment for recurrent tumors. Given the small number of cases, there are no current recommendations regarding adjuvant or salvage therapy. Initial surgery in the form of total abdominal hysterectomy and bilateral salpingo-oophorectomy should remain the most likely treatment for this rare tumor. However, patient characteristics such as age and desire for fertility should certainly be considered when formulating a treatment plan. The role for adjuvant chemotherapy or radiation therapy remains questionable. REFERENCES 1. Kariminejad MH, Scully RE. Female adnexal tumor of probable wolffian origin. Cancer 1973;31:671–7. 2. Abbot RL, Barlogie B, Schmidt WA. Metastasizing malignant juxtaovarian tumor with terminal hypercalcermia: a case report. Cancer 1981;48: 860 –5. 3. Sadler TW. Langman’s medical embryology. 5th ed. Baltimore, MD: Williams & Wilkins, 1989:258 – 68. 4. Gardner GH, Greene RR, Peckham B. Tumors of the broad ligament. Am J Obstet Gynecol 1957;73:536 –54. 5. Taxy JB, Battifora H. Female adnexal tumor of probable wolffian origin: evidence of a low-grade malignancy. Cancer 1976;37:2349 –54. 6. Rahilly MA, Williams ARW, Krausz T, Nafussi AA. Female adnexal tumor of probable wolffian origin: a clinicopathological and immunohistochemical study of three cases. Histopathology 1995;26:69 –74. 7. Devouassoux-Shisheboran M, Silver SA, Tavassoli FA. Wolffian adnexal tumor, so-called female adnexal tumor of probable wolffian origin (FATWO): immunohistochemical evidence in support of a wolffian origin. Hum Pathol 1999;30:856 – 63. 8. Moore KL. The developing human: clinically oriented embryology. 4th ed. Philadelphia: Saunders, 1988:246 – 83. 9. Young RH, Scully RE. Ovarian tumors of probable wolffian origin: a report of 11 cases. Am J Surg Pathol 1983;7:125–35. 10. Daya D, Young RH, Scully RE. Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: a report of six cases. Int J Gynecol Pathol 1992;11:122–30. 11. Daya D, Murphy J, Simon G. Paravaginal female adnexal tumor of probable wolffian origin. Am J Clin Pathol 1994;101:275– 8
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12. Sivathondan Y, Salm R, Hughesdon PE, Faccini JM. Female adnexal tumor of probable wolffian origin. J Clin Pathol 1979;32:616 –24. 13. Wagatsuma S, Yaegashi N, Namiki T, Sato S, Yajima A. A case of female adnexal tumor of probable wolffian origin: histologically, tumor cells showed three different patterns. Tohoku J Exp Med 1997;181:371–7. 14. Inoue H, Kikuchi Y, Hori T, Nabuchi K, Kobayashi M, Nagata I. An ovarian tumor of probable wolffian origin with hormonal function. Gynecol Oncol 1995;59:304 – 8. 15. Sheyn I, Mira JL, Bejarano PA, Husseinzadeh N. Metastatic female adnexal tumor of probable wolffian origin: a case report and review of the literature. Arch Pathol Lab Med 2000;124:431– 4. 16. Hinchey WW, Silva EG, Guarda LA, Ordonez NG, Wharton JT. Paravaginal wolffian duct (mesonephros) adenocarcinoma: a light and electron microscopic study. Am J Clin Pathol 1983;80:539 – 44 .
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