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Possible Metaplastic Origin of Lymph Node “Metastases” in Serous Ovarian Tumor of Low Malignant Potential (Borderline Serous Tumor)
GYNECOLOGIC ONCOLOGY
59, 394–397 (1995)
CASE REPORT Possible Metaplastic Origin of Lymph Node ‘‘Metastases’’ in Serous Ovarian Tumor of Low Malignant Potential (Borderline Serous Tumor) NICHOLAS KADAR, M.D.,*,1
MARTIN KRUMERMAN, M.D.†
AND
Division of Gynecologic Oncology, *Department of Obstetrics & Gynecology and †Department of Pathology and Laboratory Medicine, Jersey Shore Medical Center, Neptune, New Jersey 07753 Received July 13, 1994
A patient with a stage III serous ovarian carcinoma of low malignant potential (borderline serous tumor) is described who had extensive involvement of the pelvic and para-aortic lymph nodes by both borderline tumor and endosalpingiosis. Transition from endosalpingiosis to papillary serous borderline tumor was demonstrable in multiple intranodal sites, and in fully developed lesions, areas of metaplastic growth acquired a desmoplastic stroma. This finding suggests that the lymph node ‘‘metastases’’ may have arisen de novo by neoplastic transformation of preexistent metaplastic tubal-type epithelium (endosalpingiosis), and would lend further credence to the metaplastic (rather than metastatic) origin of extraovarian implants in serous ovarian carcinoma of low malignant potential. q 1995 Academic Press, Inc.
INTRODUCTION
Ovarian serous tumors of low malignant potential (borderline serous tumors) are intermediate in their clinical behavior between benign serous cystadenomas and malignant neoplasms, and are associated with overall 10-year survival rates in excess of 90%. This is only partly explained by the fact that they occur at an earlier age and present at an earlier stage than their fully malignant counterparts, for even stage III disease is associated with 10-year survival rates of at least 50% [1]. Woodruff and colleagues have attempted to explain the paradoxically favorable survival rates associated with malignancies that have ostensibly metastasized within the peritoneal cavity by suggesting that the ‘‘metastatic’’ foci in fact represent synchronous multifocal proliferations and Mu¨llerian differentiation of pluripotential coelomic epithelium at extraovarian sites [1]. This Case Report adduces evidence that pelvic and para-aortic lymph node ‘‘metasta1 To whom reprint requests should be addressed at The New Margaret Hague Women’s Health Institute, 1 Harmon Plaza, Secaucus, NJ 07094. Fax: (201) 422-0188.
10-23-95 07:46:23
CASE REPORT
A 41-year-old white female, gravida 3, para 3 presented with increasing abdominal girth and discomfort, which had been present for almost a year. The patient had been sterilized and her periods were regular. There was no significant past medical or surgical history, and no gastrointestinal symptoms were present. General examination was unremarkable except for tense ascites. An abdominal mass could not be palpated. Pelvic examination revealed an irregular, fixed pelvic mass about 20 cm in diameter, associated with nodularity in the culde-sac. The CA-125 was 371 IU/liter. Preoperative workup consisted of routine blood work, chest X ray, and electrocardiogram. The bowel was prepared mechanically and with antibiotics prior to surgery. At laparotomy approximately 10 liters of ascites were drained. There were two nodules in the omentum, measuring up to 1.8 cm in largest diameter, one of which was reported as showing Grade I metastatic serous adenocarcinoma on frozen section. All peritoneal surfaces were, however, smooth. A large irregular pelvic mass filled the cul-de-sac and showed no normal ovarian or tubal architectural landmarks. There was extensive tumor involvement of the pelvic peritoneum and sigmoid colon. The entire pelvic peritoneum was excised en bloc with the tumor, uterus, tubes, ovaries, and rectosigmoid using an extraperitoneal approach and retrograde hysterectomy. A primary stapled colorectal anastomosis was performed, and bilateral pelvic and limited, paraaortic lymphadenectomy was then carried out. The patient tolerated the procedure well, made an uncomplicated postoperative recovery and was discharged home on the fifth postoperative day. The estimated blood loss was 1.5 liters.
394
0090-8258/95 $12.00 Copyright q 1995 by Academic Press, Inc. All rights of reproduction in any form reserved.
/ m3799$4104
ses’’ in borderline serous tumors may also arise intranodally, by a similar mechanism.
goa
AP: Gyn Onc
395
CASE REPORT
FIG. 1.
Ovarian serous borderline tumor manifesting purely exophytic growth (H&E, 1100).
Pathological Findings The left adnexal area consisted of an 11-cm friable tumor mass with no grossly discernable normal ovary, which extended in a plaque-like manner along the sigmoid colon and mesentery. The right tube and ovary were unremarkable. Two nodules were noted in the omentum, The cul-de-sac tumor arose from the surface of an otherwise microscopically normal ovary, and consisted of broad papillae lined by one to four layers of tall ciliated, or eosinophilic, club-shaped, tumor cells, which lacked cellular anaplasia or evidence of significant mitotic activity (Fig. 1). There was no evidence of ovarian stroma invasion by tumor, and the peritoneal and mesocolic implants were plaque-like with smooth desmoplastic borders and no evidence of invasion. Virtually all the pelvic and para-aortic lymph nodes revealed innumerable cystic inclusions lined by tall columnar ciliated epithelial cells (endosalpingiosis) with adjacent foci of noninvasive, papillary neoplasm identical to that present in the ovary and on the pelvic peritoneal surfaces (Fig. 2). In several intranodal foci psammoma body formation by papillary tumor cell clusters was prominent. Of paramount interest, however, was the finding, in six lymph nodes, of
/ m3799$4104
10-23-95 07:46:23
goa
transitional forms between endosalpingiotic nests and sheets of proliferating papillary serous tumor, with papillae originating from the walls of preexistent glandular inclusions (Fig. 3). In fully developed lesions, the papillary component included a desmoplastic stromal reaction in the lymph nodal interstitium and underwent fibrous expansion, as in peritoneal lesions of this type (Fig. 4). DISCUSSION
Benign glandular inclusions in pelvic and aortic lymph nodes are well-recognized entities that occur exclusively in females. Their origin is uncertain, and when they are associated with well-differentiated malignancies, glandular inclusions in lymph nodes, like decidual changes, can be mistaken for metastatic carcinoma [2]. Pelvic and aortic lymph node metastases are also well known to occur in borderline tumors, and their origin is also uncertain [1, 3]. Metaplasia of the coelomic epithelium is the most widely accepted mechanism by which peritoneal implants in borderline malignancies are thought to arise. The histology of these implants, which spans a spectrum from
AP: Gyn Onc
396
KADAR AND KRUMERMAN
FIG. 2.
Pelvic lymph node. Endosalpingiosis with evolving papillary serous tumor adjascent to it (H&E, 145).
FIG. 3. Para-aortic lymph node. Transitional forms show evolution of papillary serous tumor (center) from the wall of a preexistant endosalpigiotic cyst (top and bottom) (H&E, 1100).
/ m3799$4104
10-23-95 07:46:23
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AP: Gyn Onc
397
CASE REPORT
FIG. 4. Para-aortic lymph node. Fully evolved serous neoplastic lesion showing induction of a desmoplastic fibrous stroma within the node by nests of expanding papillary and psammomatous tumor (H&E, 145).
benign glandular inclusions or ‘‘endosalpingiosis’’ to noninvasive and invasive implants, lends considerable credence to this view even if the histology of the implants has not affected survival in all series [4]. Similar histological gradations have not been reported for implants in lymph nodes. Most reports have not specified the type of metastatic lesions present in the lymph nodes (i.e., invasive or noninvasive), and all seven lymph node metastases studied by Leake et al. [1] were noninvasive. To our knowledge, this is the first report demonstrating a histological transition between benign glandular inclusions and borderline malignancy in lymph nodes, a finding that clearly suggests that lymph node metastases may in fact arise locally rather than by a metastatic process. Although the finding sheds no light on the origin of the glandular inclusions in these lymph nodes, it is well known from autopsy studies that they are not infrequently present in women who have no evidence or history of malignancy [5]. Thus, it is reasonable to postulate that the same factor(s) that triggered metaplastic proliferations in the coelomic epithelium in our patient also triggered the same process in preexistent
/ m3799$4104
10-23-95 07:46:23
goa
glandular inclusions in the lymph nodes. In as much as surgical excision, often repeated excision, is the mainstay of therapy of borderline malignancies, the present findings suggest that pelvic and aortic lymphadenectomy, rather than a sampling (‘‘staging’’) procedure may be warranted in these lesions. REFERENCES 1. Leake, J. F., Rader, J. S., Woodruff, J. D., and Rosenshein, N. B. Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential, Gynecol. Oncol. 42, 124–130 (1991). 2. Ehrmann, R. L., Federschneider, J. M., and Knapp, R. C. Distinguishing lymph node metastases from benign glandular inclusions in low-grade ovarian carcinoma, Am. J. Obstet. Gynecol. 136, 737–746 (1980). 3. Yazigi, R., Sandstad, J., and Munoz, A. K. Primary staging in ovarian tumors of low malignant potential, Gynecol. Oncol. 31, 402–408 (1988). 4. Gershenson, D. M., and Silva, E. G. Serous ovarina tumors of low malignant potential with peritoneal implants, Cancer 65, 578–585 (1990). 5. Karp, L. A., and Czernobilsky, B. Glandular inclusions in palvic and para-aortic lymph nodes, Am. J. Clin. Pathol. 52, 212–218 (1969).
AP: Gyn Onc
59, 394–397 (1995)
CASE REPORT Possible Metaplastic Origin of Lymph Node ‘‘Metastases’’ in Serous Ovarian Tumor of Low Malignant Potential (Borderline Serous Tumor) NICHOLAS KADAR, M.D.,*,1
MARTIN KRUMERMAN, M.D.†
AND
Division of Gynecologic Oncology, *Department of Obstetrics & Gynecology and †Department of Pathology and Laboratory Medicine, Jersey Shore Medical Center, Neptune, New Jersey 07753 Received July 13, 1994
A patient with a stage III serous ovarian carcinoma of low malignant potential (borderline serous tumor) is described who had extensive involvement of the pelvic and para-aortic lymph nodes by both borderline tumor and endosalpingiosis. Transition from endosalpingiosis to papillary serous borderline tumor was demonstrable in multiple intranodal sites, and in fully developed lesions, areas of metaplastic growth acquired a desmoplastic stroma. This finding suggests that the lymph node ‘‘metastases’’ may have arisen de novo by neoplastic transformation of preexistent metaplastic tubal-type epithelium (endosalpingiosis), and would lend further credence to the metaplastic (rather than metastatic) origin of extraovarian implants in serous ovarian carcinoma of low malignant potential. q 1995 Academic Press, Inc.
INTRODUCTION
Ovarian serous tumors of low malignant potential (borderline serous tumors) are intermediate in their clinical behavior between benign serous cystadenomas and malignant neoplasms, and are associated with overall 10-year survival rates in excess of 90%. This is only partly explained by the fact that they occur at an earlier age and present at an earlier stage than their fully malignant counterparts, for even stage III disease is associated with 10-year survival rates of at least 50% [1]. Woodruff and colleagues have attempted to explain the paradoxically favorable survival rates associated with malignancies that have ostensibly metastasized within the peritoneal cavity by suggesting that the ‘‘metastatic’’ foci in fact represent synchronous multifocal proliferations and Mu¨llerian differentiation of pluripotential coelomic epithelium at extraovarian sites [1]. This Case Report adduces evidence that pelvic and para-aortic lymph node ‘‘metasta1 To whom reprint requests should be addressed at The New Margaret Hague Women’s Health Institute, 1 Harmon Plaza, Secaucus, NJ 07094. Fax: (201) 422-0188.
10-23-95 07:46:23
CASE REPORT
A 41-year-old white female, gravida 3, para 3 presented with increasing abdominal girth and discomfort, which had been present for almost a year. The patient had been sterilized and her periods were regular. There was no significant past medical or surgical history, and no gastrointestinal symptoms were present. General examination was unremarkable except for tense ascites. An abdominal mass could not be palpated. Pelvic examination revealed an irregular, fixed pelvic mass about 20 cm in diameter, associated with nodularity in the culde-sac. The CA-125 was 371 IU/liter. Preoperative workup consisted of routine blood work, chest X ray, and electrocardiogram. The bowel was prepared mechanically and with antibiotics prior to surgery. At laparotomy approximately 10 liters of ascites were drained. There were two nodules in the omentum, measuring up to 1.8 cm in largest diameter, one of which was reported as showing Grade I metastatic serous adenocarcinoma on frozen section. All peritoneal surfaces were, however, smooth. A large irregular pelvic mass filled the cul-de-sac and showed no normal ovarian or tubal architectural landmarks. There was extensive tumor involvement of the pelvic peritoneum and sigmoid colon. The entire pelvic peritoneum was excised en bloc with the tumor, uterus, tubes, ovaries, and rectosigmoid using an extraperitoneal approach and retrograde hysterectomy. A primary stapled colorectal anastomosis was performed, and bilateral pelvic and limited, paraaortic lymphadenectomy was then carried out. The patient tolerated the procedure well, made an uncomplicated postoperative recovery and was discharged home on the fifth postoperative day. The estimated blood loss was 1.5 liters.
394
0090-8258/95 $12.00 Copyright q 1995 by Academic Press, Inc. All rights of reproduction in any form reserved.
/ m3799$4104
ses’’ in borderline serous tumors may also arise intranodally, by a similar mechanism.
goa
AP: Gyn Onc
395
CASE REPORT
FIG. 1.
Ovarian serous borderline tumor manifesting purely exophytic growth (H&E, 1100).
Pathological Findings The left adnexal area consisted of an 11-cm friable tumor mass with no grossly discernable normal ovary, which extended in a plaque-like manner along the sigmoid colon and mesentery. The right tube and ovary were unremarkable. Two nodules were noted in the omentum, The cul-de-sac tumor arose from the surface of an otherwise microscopically normal ovary, and consisted of broad papillae lined by one to four layers of tall ciliated, or eosinophilic, club-shaped, tumor cells, which lacked cellular anaplasia or evidence of significant mitotic activity (Fig. 1). There was no evidence of ovarian stroma invasion by tumor, and the peritoneal and mesocolic implants were plaque-like with smooth desmoplastic borders and no evidence of invasion. Virtually all the pelvic and para-aortic lymph nodes revealed innumerable cystic inclusions lined by tall columnar ciliated epithelial cells (endosalpingiosis) with adjacent foci of noninvasive, papillary neoplasm identical to that present in the ovary and on the pelvic peritoneal surfaces (Fig. 2). In several intranodal foci psammoma body formation by papillary tumor cell clusters was prominent. Of paramount interest, however, was the finding, in six lymph nodes, of
/ m3799$4104
10-23-95 07:46:23
goa
transitional forms between endosalpingiotic nests and sheets of proliferating papillary serous tumor, with papillae originating from the walls of preexistent glandular inclusions (Fig. 3). In fully developed lesions, the papillary component included a desmoplastic stromal reaction in the lymph nodal interstitium and underwent fibrous expansion, as in peritoneal lesions of this type (Fig. 4). DISCUSSION
Benign glandular inclusions in pelvic and aortic lymph nodes are well-recognized entities that occur exclusively in females. Their origin is uncertain, and when they are associated with well-differentiated malignancies, glandular inclusions in lymph nodes, like decidual changes, can be mistaken for metastatic carcinoma [2]. Pelvic and aortic lymph node metastases are also well known to occur in borderline tumors, and their origin is also uncertain [1, 3]. Metaplasia of the coelomic epithelium is the most widely accepted mechanism by which peritoneal implants in borderline malignancies are thought to arise. The histology of these implants, which spans a spectrum from
AP: Gyn Onc
396
KADAR AND KRUMERMAN
FIG. 2.
Pelvic lymph node. Endosalpingiosis with evolving papillary serous tumor adjascent to it (H&E, 145).
FIG. 3. Para-aortic lymph node. Transitional forms show evolution of papillary serous tumor (center) from the wall of a preexistant endosalpigiotic cyst (top and bottom) (H&E, 1100).
/ m3799$4104
10-23-95 07:46:23
goa
AP: Gyn Onc
397
CASE REPORT
FIG. 4. Para-aortic lymph node. Fully evolved serous neoplastic lesion showing induction of a desmoplastic fibrous stroma within the node by nests of expanding papillary and psammomatous tumor (H&E, 145).
benign glandular inclusions or ‘‘endosalpingiosis’’ to noninvasive and invasive implants, lends considerable credence to this view even if the histology of the implants has not affected survival in all series [4]. Similar histological gradations have not been reported for implants in lymph nodes. Most reports have not specified the type of metastatic lesions present in the lymph nodes (i.e., invasive or noninvasive), and all seven lymph node metastases studied by Leake et al. [1] were noninvasive. To our knowledge, this is the first report demonstrating a histological transition between benign glandular inclusions and borderline malignancy in lymph nodes, a finding that clearly suggests that lymph node metastases may in fact arise locally rather than by a metastatic process. Although the finding sheds no light on the origin of the glandular inclusions in these lymph nodes, it is well known from autopsy studies that they are not infrequently present in women who have no evidence or history of malignancy [5]. Thus, it is reasonable to postulate that the same factor(s) that triggered metaplastic proliferations in the coelomic epithelium in our patient also triggered the same process in preexistent
/ m3799$4104
10-23-95 07:46:23
goa
glandular inclusions in the lymph nodes. In as much as surgical excision, often repeated excision, is the mainstay of therapy of borderline malignancies, the present findings suggest that pelvic and aortic lymphadenectomy, rather than a sampling (‘‘staging’’) procedure may be warranted in these lesions. REFERENCES 1. Leake, J. F., Rader, J. S., Woodruff, J. D., and Rosenshein, N. B. Retroperitoneal lymphatic involvement with epithelial ovarian tumors of low malignant potential, Gynecol. Oncol. 42, 124–130 (1991). 2. Ehrmann, R. L., Federschneider, J. M., and Knapp, R. C. Distinguishing lymph node metastases from benign glandular inclusions in low-grade ovarian carcinoma, Am. J. Obstet. Gynecol. 136, 737–746 (1980). 3. Yazigi, R., Sandstad, J., and Munoz, A. K. Primary staging in ovarian tumors of low malignant potential, Gynecol. Oncol. 31, 402–408 (1988). 4. Gershenson, D. M., and Silva, E. G. Serous ovarina tumors of low malignant potential with peritoneal implants, Cancer 65, 578–585 (1990). 5. Karp, L. A., and Czernobilsky, B. Glandular inclusions in palvic and para-aortic lymph nodes, Am. J. Clin. Pathol. 52, 212–218 (1969).
AP: Gyn Onc