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Jejunal Adenocarcinoma Presenting as a Primary Ovarian Carcinoma
Gynecologic Oncology 78, 255–258 (2000) doi:10.1006/gyno.2000.5872, available online at http://www.idealibrary.com on
CASE REPORT Jejunal Adenocarcinoma Presenting as a Primary Ovarian Carcinoma Gokhan Kilic, M.D., and Maria Abadi, M.D. Department of Pathology, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, 10461 Received October 12, 1999
Although small bowel constitutes 75% of the length and 90% of the mucosal surface of the alimentary tract, small bowel malignancies account only for 3% of all gastrointestinal malignancies [1]. The vast majority of them are located in the duodenojejunal area. We describe a case of a primary jejunal adenocarcinoma which presented with bowel obstruction due to a colossal ovarian mass.
Objective. The aim of this case report was to evaluate the impact of immunohistochemical markers in diagnosing the primary site of adenocarcinoma in the abdominopelvic region. Methods. Surgicopathologic data were obtained from laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was stained with hematoxylin and eosin, as well as with immunohistochemical stains for cytokeratin 20 and cytokeratin 7. Results. A 53-year-old African American woman underwent an emergency laparotomy due to small bowel obstruction. During the operation, in addition to a complex adnexal mass as the cause of obstruction, a small solid jejunal tumor was also identified. Pathologic evaluation of the two sites demonstrated an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed negative staining for cytokeratin 7. These results confirmed the diagnosis of intestinal primary with ovarian metastasis, which was initially misdiagnosed as an ovarian primary. Conclusion. Given the potential difficulty in determining the primary site of these tumors, immunohistochemistry proved to be a useful tool in reaching the correct diagnosis. © 2000 Academic Press Key Words: adenocarcinoma; small bowel; ovary.
CASE REPORT
INTRODUCTION
A 53-year-old African American woman presented with a 6-day history of abdominal pain in the periumbilical area, vomiting, and no bowel movements. Physical examination revealed moderate abdominal tenderness and a large, firm abdominal mass. Abdominal and pelvic computed tomography demonstrated small bowel obstruction due to a large heterogeneous mass, likely of ovarian origin. The patient required laparotomy for the obstruction. The right ovary showed two solid, partly cystic, necrotic masses measuring 20 ⫻ 18 ⫻ 15 and 15 ⫻ 13 ⫻ 10 cm, respectively (Fig. 1). During the bowel examination at the time of the operation, a small solid mass measuring 3 cm in greatest dimension was palpated in the jejunum, which necessitated a partial jejunectomy in addition to a right oophorectomy (Fig. 2). The permanent microscopic sections showed an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features involving the small bowel, right ovary, and pelvis (Fig. 3). The jejunal tumor invaded deeply into the intestinal wall, but did not extend beyond the serosa. Extensive lympovascular invasion was noted, but the pericolonic lymph nodes were not involved with metastatic disease. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 (CK20) and revealed negative staining for cytokeratin 7 (CK7). Based on this immunohistochemical profile, the diagnosis of intestinal primary with ovarian metastasis was made. The patient died 6 days after the surgical procedure due to pulmonary emboli, despite prophylaxis with anticoagulants. The autopsy revealed 1500 ml of serosanguineous abdominal fluid and a multiloculated, extensively necrotic mass involving the lower third of
Metastatic ovarian neoplasia constitutes 3 to 8% of all ovarian tumors and 10 to 30% of all malignant ovarian tumors. The most common extragenital primary sites are colon, stomach, and breast. The entity of Krukenberg’s tumor was described as metastatic carcinoma involving the ovaries with signet ring cells and diffuse stromal infiltration. Krukenberg’s tumor can be associated with virtually any mucin-producing adenocarcinoma. The primary sites in the gastrointestinal tract include stomach, small bowel, gallbladder, appendix, and pancreas, with 80% arising in the stomach. Non-Krukenberg’s gastrointestinal primaries include colon and rectum, which are even more common than the stomach. These metastases appear to retain the characteristic microscopic picture of the primary tumor. In either case, metastatic carcinoma to the ovary from the small bowel is extremely rare. 255
0090-8258/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
256
KILIC AND ABADI
FIG. 1.
Sectioned surface of the jejunum showing a lobulated, solid mass not extending beyond the serosa.
the ureters, parametria, and Douglas’ pouch. The left ovary and uterus were grossly normal except for an intramural leiomyoma. The microscopic evaluation was consistent with the previous diagnosis of adenocarcinoma of small intestine metastatic to the right ovary and pelvis. DISCUSSION Small bowel malignancies are uncommon and the reported incidence comprises 3% of all gastrointestinal malignancies
and 0.1 to 0.33% of all malignancies [1, 2]. Wingo et al. reported that 4600 cases of small bowel cancer are diagnosed annually in contrast to an estimated 138,200 of new cases of colorectal cancer a year [3]. Despite the fact that adenocarcinomas and carcinoids are the most frequently diagnosed primary small bowel malignancies (55 to 90%), their incidence is 6.9 cases per million persons per year in the United States [2]. Furthermore, only 1% of the adenocarcinomas of the gastrointestinal tract arise from the small bowel [4]. Because of the
FIG. 2. Histologic section of ovarian specimen demonstrating well-differentiated adenocarcinoma with mucinous features along with high nuclear to cytoplasmic ratio and hyperchromatic nuclei (H&E 40⫻).
CASE REPORT
FIG. 3.
257
Sectioned surface of the right adnexal mass showing a multiloculated tumor which is solid and cystic with areas of necrosis and hemorrhage.
rarity of the small bowel carcinoma and the late onset of symptoms, it is usually diagnosed when it is already metastatic. Therefore, the 5-year survival rate remains low (28%). The reason for being asymptomatic at the early stages is the ability of the tumor to distend the bowel wall and the already liquefied luminal contents. The most common presentation is mechanical obstruction followed by gastrointestinal bleeding, weight loss, palpable abdominal mass, jaundice, or pancreatitis. Detection of small bowel carcinomas by upper gastrointestinal barium studies is not entirely satisfactory, being diagnostic in approximately 56% of the cases [5]. In addition, even with the contribution of imaging studies, it is difficult to exclude metastatic ovarian cancer [6]. Approximately 10 to 30% of reported ovarian cancers are metastatic, yet the diagnosis continues to be a problem. Autopsy studies on patients dying of cancer suggest that metastatic carcinomas in the ovary are more common than primary ones [7, 8]. The usual primary sites are colon, breast, stomach, and uterus. Patients with metastatic ovarian cancer are younger than those with primary ovarian cancers even though more than 50% of them are postmenopausal at the time of diagnosis. Marked enlargement of the ovaries secondary to metastatic cancer from a gastrointestinal primary may present with nonspecific gastrointestinal symptoms. This is thought to be due to the obstruction of lymphatics by tumor emboli causing fastgrowing ovarian masses. The current data suggest that there are three major routes of metastasis to the ovary from the gastrointestinal system: (1) retrograde lymphatic spread, (2) dissemination through peritoneal fluid, and (3) hematogenous spread [9]. The lymphatic network from the ovary meets with lymphatics from the mesenteric axis in the aortic pathways allowing for metastatic spread. This theory applies to very small primary tumors in the gastrointestinal tract, such as the present
case, in which ovarian metastases are discovered before the primary site can be determined. The most likely route of spread in this case is through the lymphatics since the jejunal tumor did not extend beyond the serosa and showed extensive lymphatic invasion. Among the several methods for differentiating between gastrointestinal and ovary primaries, immunohistochemistry is perhaps the most reliable. Colonic carcinomas are typically positive for carcinoembryonic antigen (CEA) and CK20 and negative for CK7 and CA125. However, Heald et al. indicated that CEA is also positive in at least 80% of primary ovarian mucinous carcinomas [11]. By contrast, Daya et al. showed strong intracytoplasmic positive staining for CEA in all cases of metastatic intestinal adenocarcinoma, while CEA was either negative or showed intraluminal or apical positivity in primary ovarian adenocarcinoma [10]. In addition to the localization of the staining in the malignant cells, another use for CEA comes from the fact that it is usually seen in invasive mucinous tumors but is very rare in benign mucinous cystadenomas. CA125 antigen, on the other hand, is positive in the vast majority of serous ovarian carcinomas but is less useful in mucinous carcinomas [12]. It’s overall sensitivity ranges from 70 to 90%, and its specificity ranges from 69 to 92% in ovarian cancers [13]. Sack et al. demonstrated that the combined use of CK20 and CK7 antibodies is highly sensitive (100%) and specific (100%) for metastatic colonic adenocarcinoma in 7 cytologic specimens [14]. In the same study, strong positivity for CK7 was seen in all metastatic ovarian carcinomas. Moll et al. applied CK20 on 93 colonic carcinomas and noted positive staining in 89 of them [15]. Loy and Calalaluce described lower specifities for these antibodies than previously reported [16]. In their
258
KILIC AND ABADI
series, 98% of 77 colonic carcinoma cases were CK20 positive; however, 21% also showed CK7 positivity. Lagendijk et al. recently showed that, for discrimination purposes, the best combination of markers is CK7 and CEA [17]. Furthermore, CK20 immunoreactivity is equivocal to CEA. Only a few mucinous ovarian carcinomas resemble colonic carcinomas in their staining pattern: strong and diffuse CEA and CK20 positivity and low CK7 content. Distinguishing a secondary ovarian tumor from a primary ovarian tumor is crucial for appropriate treatment. To improve outcome, the diagnosis must be made at an early stage. In addition to intraoperative small bowel examination, since many ovaries containing metastatic foci have a normal gross appearance, careful microscopic analysis is essential to discover occult metastasis. REFERENCES 1. Hart R, Levin B: Neoplasms of the small intestine, in Calabresi P, Schein PS (eds): Medical Oncology, New York, NY, McGraw–Hill, 1993, p 741 2. Lowenfels AB: Why are small-bowel tumours so rare? Lancet 1:24, 1973 3. Wingo PA, Tong T, Bolden S: Cancer statistics. CA Cancer J Clin 45(2):127–128, 1995 4. Ellis DJ. Small bowel carcinomas, in Fielding JWL, Priestman TJ (eds): Gastrointestinal Oncology. Philadelphia, PA, Lea & Febiger, 1986, p 196 5. Martin LF, Max MH, Richardson JD, Peterson GH: Small bowel tumors: a continuing challenge. South Med J 73(8):981–985, 1980 6. Tsuruchi N, Kubota H, Tsukamoto N, Kurano A: Primary jejunal adenocarcinoma masquerading as a primary ovarian malignancy. Gynecol Oncol 58:129 –132, 1995
7. Israel SL, Helsel EV, Hausman DA 1965. The challenge of metastatic ovarian carcinoma. Am J Obstet Gynecol 93:1094, 1965 8. Athey PA, Butters HE 1984. Sonographic and CT appearance of Krukenberg tumors. J Clin Ultrasound 12:205–209, 1984 9. Chang TC, Changchien CC, Tseng CW, Lai CH, Tseng CJ, Lin SE, Wang CS, Huang KJ, Chou HH, Ma YY, Hsueh S, Eng HL, Fan HA: Retrograde lymphatic spread: a likely route for metastatic ovarian cancers of gastrointestinal origin. Gynecol Oncol 66:372–377, 1997 10. Daya D, Nazerali L, Frank GL: Metastatic ovarian carcinoma of large intestinal origin simulating primary ovarian carcinoma. Am J Clin Pathol 97:751–758, 1992 11. Heald J, Buckley CH, Fox H: An immunohistochemical study of the distribution of carcinoembryonic antigen in epithelial tumors of the ovary. J Clin Pathol 32:918 –926, 1979 12. Lin M, Hanai J, Wada A: A comparative immunohistochemical study of 135 cases. Acta Pathol Japon 41:233–239, 1991 13. Zanaboni F, Vergadoro F, Presti M, Gallotti P, Lombardi F, Bolis G: Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma. Gynecol Oncol 28:61– 67, 1987 14. Sack MJ, Roberts SA: Cytokeratin 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens. Diagn Cytopathol 16:132– 136, 1997 15. Moll R, Lowe A, Laufer J, Franke WW: Cytokeratin 20 in human carcinomas. Am J Pathol 140:427– 447, 1992 16. Loy T, Calalaluce R: Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic adenocarcinomas. Mod Pathol 7:165A, 1994 17. Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ: Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 29:491– 497, 1998
CASE REPORT Jejunal Adenocarcinoma Presenting as a Primary Ovarian Carcinoma Gokhan Kilic, M.D., and Maria Abadi, M.D. Department of Pathology, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, 10461 Received October 12, 1999
Although small bowel constitutes 75% of the length and 90% of the mucosal surface of the alimentary tract, small bowel malignancies account only for 3% of all gastrointestinal malignancies [1]. The vast majority of them are located in the duodenojejunal area. We describe a case of a primary jejunal adenocarcinoma which presented with bowel obstruction due to a colossal ovarian mass.
Objective. The aim of this case report was to evaluate the impact of immunohistochemical markers in diagnosing the primary site of adenocarcinoma in the abdominopelvic region. Methods. Surgicopathologic data were obtained from laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was stained with hematoxylin and eosin, as well as with immunohistochemical stains for cytokeratin 20 and cytokeratin 7. Results. A 53-year-old African American woman underwent an emergency laparotomy due to small bowel obstruction. During the operation, in addition to a complex adnexal mass as the cause of obstruction, a small solid jejunal tumor was also identified. Pathologic evaluation of the two sites demonstrated an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed negative staining for cytokeratin 7. These results confirmed the diagnosis of intestinal primary with ovarian metastasis, which was initially misdiagnosed as an ovarian primary. Conclusion. Given the potential difficulty in determining the primary site of these tumors, immunohistochemistry proved to be a useful tool in reaching the correct diagnosis. © 2000 Academic Press Key Words: adenocarcinoma; small bowel; ovary.
CASE REPORT
INTRODUCTION
A 53-year-old African American woman presented with a 6-day history of abdominal pain in the periumbilical area, vomiting, and no bowel movements. Physical examination revealed moderate abdominal tenderness and a large, firm abdominal mass. Abdominal and pelvic computed tomography demonstrated small bowel obstruction due to a large heterogeneous mass, likely of ovarian origin. The patient required laparotomy for the obstruction. The right ovary showed two solid, partly cystic, necrotic masses measuring 20 ⫻ 18 ⫻ 15 and 15 ⫻ 13 ⫻ 10 cm, respectively (Fig. 1). During the bowel examination at the time of the operation, a small solid mass measuring 3 cm in greatest dimension was palpated in the jejunum, which necessitated a partial jejunectomy in addition to a right oophorectomy (Fig. 2). The permanent microscopic sections showed an infiltrating moderately to poorly differentiated adenocarcinoma with mucinous features involving the small bowel, right ovary, and pelvis (Fig. 3). The jejunal tumor invaded deeply into the intestinal wall, but did not extend beyond the serosa. Extensive lympovascular invasion was noted, but the pericolonic lymph nodes were not involved with metastatic disease. The malignant cells from both intestinal and ovarian sites showed immunoreactivity for cytokeratin 20 (CK20) and revealed negative staining for cytokeratin 7 (CK7). Based on this immunohistochemical profile, the diagnosis of intestinal primary with ovarian metastasis was made. The patient died 6 days after the surgical procedure due to pulmonary emboli, despite prophylaxis with anticoagulants. The autopsy revealed 1500 ml of serosanguineous abdominal fluid and a multiloculated, extensively necrotic mass involving the lower third of
Metastatic ovarian neoplasia constitutes 3 to 8% of all ovarian tumors and 10 to 30% of all malignant ovarian tumors. The most common extragenital primary sites are colon, stomach, and breast. The entity of Krukenberg’s tumor was described as metastatic carcinoma involving the ovaries with signet ring cells and diffuse stromal infiltration. Krukenberg’s tumor can be associated with virtually any mucin-producing adenocarcinoma. The primary sites in the gastrointestinal tract include stomach, small bowel, gallbladder, appendix, and pancreas, with 80% arising in the stomach. Non-Krukenberg’s gastrointestinal primaries include colon and rectum, which are even more common than the stomach. These metastases appear to retain the characteristic microscopic picture of the primary tumor. In either case, metastatic carcinoma to the ovary from the small bowel is extremely rare. 255
0090-8258/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.
256
KILIC AND ABADI
FIG. 1.
Sectioned surface of the jejunum showing a lobulated, solid mass not extending beyond the serosa.
the ureters, parametria, and Douglas’ pouch. The left ovary and uterus were grossly normal except for an intramural leiomyoma. The microscopic evaluation was consistent with the previous diagnosis of adenocarcinoma of small intestine metastatic to the right ovary and pelvis. DISCUSSION Small bowel malignancies are uncommon and the reported incidence comprises 3% of all gastrointestinal malignancies
and 0.1 to 0.33% of all malignancies [1, 2]. Wingo et al. reported that 4600 cases of small bowel cancer are diagnosed annually in contrast to an estimated 138,200 of new cases of colorectal cancer a year [3]. Despite the fact that adenocarcinomas and carcinoids are the most frequently diagnosed primary small bowel malignancies (55 to 90%), their incidence is 6.9 cases per million persons per year in the United States [2]. Furthermore, only 1% of the adenocarcinomas of the gastrointestinal tract arise from the small bowel [4]. Because of the
FIG. 2. Histologic section of ovarian specimen demonstrating well-differentiated adenocarcinoma with mucinous features along with high nuclear to cytoplasmic ratio and hyperchromatic nuclei (H&E 40⫻).
CASE REPORT
FIG. 3.
257
Sectioned surface of the right adnexal mass showing a multiloculated tumor which is solid and cystic with areas of necrosis and hemorrhage.
rarity of the small bowel carcinoma and the late onset of symptoms, it is usually diagnosed when it is already metastatic. Therefore, the 5-year survival rate remains low (28%). The reason for being asymptomatic at the early stages is the ability of the tumor to distend the bowel wall and the already liquefied luminal contents. The most common presentation is mechanical obstruction followed by gastrointestinal bleeding, weight loss, palpable abdominal mass, jaundice, or pancreatitis. Detection of small bowel carcinomas by upper gastrointestinal barium studies is not entirely satisfactory, being diagnostic in approximately 56% of the cases [5]. In addition, even with the contribution of imaging studies, it is difficult to exclude metastatic ovarian cancer [6]. Approximately 10 to 30% of reported ovarian cancers are metastatic, yet the diagnosis continues to be a problem. Autopsy studies on patients dying of cancer suggest that metastatic carcinomas in the ovary are more common than primary ones [7, 8]. The usual primary sites are colon, breast, stomach, and uterus. Patients with metastatic ovarian cancer are younger than those with primary ovarian cancers even though more than 50% of them are postmenopausal at the time of diagnosis. Marked enlargement of the ovaries secondary to metastatic cancer from a gastrointestinal primary may present with nonspecific gastrointestinal symptoms. This is thought to be due to the obstruction of lymphatics by tumor emboli causing fastgrowing ovarian masses. The current data suggest that there are three major routes of metastasis to the ovary from the gastrointestinal system: (1) retrograde lymphatic spread, (2) dissemination through peritoneal fluid, and (3) hematogenous spread [9]. The lymphatic network from the ovary meets with lymphatics from the mesenteric axis in the aortic pathways allowing for metastatic spread. This theory applies to very small primary tumors in the gastrointestinal tract, such as the present
case, in which ovarian metastases are discovered before the primary site can be determined. The most likely route of spread in this case is through the lymphatics since the jejunal tumor did not extend beyond the serosa and showed extensive lymphatic invasion. Among the several methods for differentiating between gastrointestinal and ovary primaries, immunohistochemistry is perhaps the most reliable. Colonic carcinomas are typically positive for carcinoembryonic antigen (CEA) and CK20 and negative for CK7 and CA125. However, Heald et al. indicated that CEA is also positive in at least 80% of primary ovarian mucinous carcinomas [11]. By contrast, Daya et al. showed strong intracytoplasmic positive staining for CEA in all cases of metastatic intestinal adenocarcinoma, while CEA was either negative or showed intraluminal or apical positivity in primary ovarian adenocarcinoma [10]. In addition to the localization of the staining in the malignant cells, another use for CEA comes from the fact that it is usually seen in invasive mucinous tumors but is very rare in benign mucinous cystadenomas. CA125 antigen, on the other hand, is positive in the vast majority of serous ovarian carcinomas but is less useful in mucinous carcinomas [12]. It’s overall sensitivity ranges from 70 to 90%, and its specificity ranges from 69 to 92% in ovarian cancers [13]. Sack et al. demonstrated that the combined use of CK20 and CK7 antibodies is highly sensitive (100%) and specific (100%) for metastatic colonic adenocarcinoma in 7 cytologic specimens [14]. In the same study, strong positivity for CK7 was seen in all metastatic ovarian carcinomas. Moll et al. applied CK20 on 93 colonic carcinomas and noted positive staining in 89 of them [15]. Loy and Calalaluce described lower specifities for these antibodies than previously reported [16]. In their
258
KILIC AND ABADI
series, 98% of 77 colonic carcinoma cases were CK20 positive; however, 21% also showed CK7 positivity. Lagendijk et al. recently showed that, for discrimination purposes, the best combination of markers is CK7 and CEA [17]. Furthermore, CK20 immunoreactivity is equivocal to CEA. Only a few mucinous ovarian carcinomas resemble colonic carcinomas in their staining pattern: strong and diffuse CEA and CK20 positivity and low CK7 content. Distinguishing a secondary ovarian tumor from a primary ovarian tumor is crucial for appropriate treatment. To improve outcome, the diagnosis must be made at an early stage. In addition to intraoperative small bowel examination, since many ovaries containing metastatic foci have a normal gross appearance, careful microscopic analysis is essential to discover occult metastasis. REFERENCES 1. Hart R, Levin B: Neoplasms of the small intestine, in Calabresi P, Schein PS (eds): Medical Oncology, New York, NY, McGraw–Hill, 1993, p 741 2. Lowenfels AB: Why are small-bowel tumours so rare? Lancet 1:24, 1973 3. Wingo PA, Tong T, Bolden S: Cancer statistics. CA Cancer J Clin 45(2):127–128, 1995 4. Ellis DJ. Small bowel carcinomas, in Fielding JWL, Priestman TJ (eds): Gastrointestinal Oncology. Philadelphia, PA, Lea & Febiger, 1986, p 196 5. Martin LF, Max MH, Richardson JD, Peterson GH: Small bowel tumors: a continuing challenge. South Med J 73(8):981–985, 1980 6. Tsuruchi N, Kubota H, Tsukamoto N, Kurano A: Primary jejunal adenocarcinoma masquerading as a primary ovarian malignancy. Gynecol Oncol 58:129 –132, 1995
7. Israel SL, Helsel EV, Hausman DA 1965. The challenge of metastatic ovarian carcinoma. Am J Obstet Gynecol 93:1094, 1965 8. Athey PA, Butters HE 1984. Sonographic and CT appearance of Krukenberg tumors. J Clin Ultrasound 12:205–209, 1984 9. Chang TC, Changchien CC, Tseng CW, Lai CH, Tseng CJ, Lin SE, Wang CS, Huang KJ, Chou HH, Ma YY, Hsueh S, Eng HL, Fan HA: Retrograde lymphatic spread: a likely route for metastatic ovarian cancers of gastrointestinal origin. Gynecol Oncol 66:372–377, 1997 10. Daya D, Nazerali L, Frank GL: Metastatic ovarian carcinoma of large intestinal origin simulating primary ovarian carcinoma. Am J Clin Pathol 97:751–758, 1992 11. Heald J, Buckley CH, Fox H: An immunohistochemical study of the distribution of carcinoembryonic antigen in epithelial tumors of the ovary. J Clin Pathol 32:918 –926, 1979 12. Lin M, Hanai J, Wada A: A comparative immunohistochemical study of 135 cases. Acta Pathol Japon 41:233–239, 1991 13. Zanaboni F, Vergadoro F, Presti M, Gallotti P, Lombardi F, Bolis G: Tumor antigen CA 125 as a marker of ovarian epithelial carcinoma. Gynecol Oncol 28:61– 67, 1987 14. Sack MJ, Roberts SA: Cytokeratin 20 and 7 in the differential diagnosis of metastatic carcinoma in cytologic specimens. Diagn Cytopathol 16:132– 136, 1997 15. Moll R, Lowe A, Laufer J, Franke WW: Cytokeratin 20 in human carcinomas. Am J Pathol 140:427– 447, 1992 16. Loy T, Calalaluce R: Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic adenocarcinomas. Mod Pathol 7:165A, 1994 17. Lagendijk JH, Mullink H, Van Diest PJ, Meijer GA, Meijer CJ: Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas as primary sites. Hum Pathol 29:491– 497, 1998